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DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with AFRICURE PHARMA, ROW2TECH, NIPER-G, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Govt. of India as ADVISOR, earlier assignment was
with GLENMARK LIFE SCIENCES LTD, as CONSUlTANT, Retired from GLENMARK in Jan2022 Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 32 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international,
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and implementation them on commercial scale over a 32 PLUS year tenure till date Feb 2023, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 100 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 100 Lakh plus views on dozen plus blogs, 227 countries, 7 continents, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 38 lakh plus views on New Drug Approvals Blog in 227 countries......https://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc
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Safe and effective vaccines are needed to end the COVID-19 pandemic caused by SARS-CoV-2. Here we report the preclinical development of a lipid nanoparticle (LNP) formulated SARS-CoV-2 mRNA vaccine, PTX-COVID19-B. PTX-COVID19-B was chosen among three candidates after the initial mouse vaccination results showed that it elicited the strongest neutralizing antibody response against SARS-CoV-2. Further tests in mice and hamsters indicated that PTX-COVID19-B induced robust humoral and cellular immune responses and completely protected the vaccinated animals from SARS-CoV-2 infection in the lung. Studies in hamsters also showed that PTX-COVID19-B protected the upper respiratory tract from SARS-CoV-2 infection. Mouse immune sera elicited by PTX-COVID19-B vaccination were able to neutralize SARS-CoV-2 variants of concern (VOCs), including the B.1.1.7, B.1.351 and P.1 lineages. No adverse effects were induced by PTX-COVID19-B in both mice and hamsters. These preclinical results indicate that PTX-COVID19-B is safe and effective. Based on these results, PTX-COVID19-B was authorized by Health Canada to enter clinical trials in December 2020 with a phase 1 clinical trial ongoing (ClinicalTrials.gov number: NCT04765436).
PTX-COVID19-B is a messenger RNA (mRNA)-based COVID-19 vaccine, a vaccine for the prevention of the COVID-19 disease caused by an infection of the SARS-CoV-2coronavirus, created by Providence Therapeutics—a private Canadian drug company co-founded by Calgary, Alberta-based businessman Brad T. Sorenson and San Francisco-based Eric Marcusson.[1] in 2013. A team of eighteen working out of Sunnybrook Research Institute in Toronto, Ontario developed PTX-COVID19-B[2] in less than four weeks, according to the Calgary Herald.[3] Human trials with sixty volunteers began on January 26, 2021 in Toronto.[4][5][6]
Providence, which has no manufacturing facilities, partnered with Calgary-based Northern mRNA—the “anchor tenant” in their future manufacturing facilities pending financing.[2]
On 30 April 2021, Sorenson announced that Providence Therapeutics would be leaving Canada and any vaccine that it developed would not be manufactured in Canada.[2]
Overview
Providence Therapeutics Holdings Inc. was co-founded in Toronto, Ontario[7][8] by Calgary, Alberta-based businessman Brad T. Sorenson and San Francisco-based Eric Marcusson Ph.D, who was also the Chief Scientific Officer.[9][3]
PTX-COVID19-B is a messenger RNA (mRNA)-based COVID-19 vaccine. In an interview with CTV news, Sorenson said they were “building some of the important building blocks for the messenger RNA … that provides instructions to cells … to build proteins that may treat or prevent disease”.
As of January 2021, Northern RNA’s Calgary lab was proposed as the site where manufacturing of PTX-COVID19-B would take place.[10] Providence Therapeutics’ partner, Northern RNA, which located at 421 7 Avenue SW in Calgary, has been described as Providence Therapeutics northern division.[7][8]
A February 2021 Manitoba government press release said that the Winnipeg-based Emergent BioSolutions would be manufacturing the vaccine.[11]
Human trials
Phase 1
Human trials began on January 26, 2021 with 60 volunteers between the ages of 18 to 65 in Toronto.[12][13][3] Of these, 15 would receive a placebo and 3 groups of 15 would receive different doses of the vaccine.[10] The volunteers will be monitored for 13 months. The company said that enough data would be available in May which could result in a Phase 2 clinical testing beginning soon after that, pending regulatory approval. If the results of a subsequent larger human trial are positive, the vaccine could enter a commercialization phase in 2022.[14] The Phase 1 clinical trial lead was Piyush Patel. At the 29 April meeting with the House of Commons, Sorenson estimated that PTX-COVID19-B could be approved by Health Canada by “January or February 2022”.[15]:8
Provincial funding
Shortly after the first human trials on PTX-COVID19-B began in late January, on 11 February 2021, Manitoba Premier Brian Pallister announced a “term sheet” between the province and Providence Therapeutics through which Manitoba would receive 2 million doses of PTX-COVID19-B pending its approval by Health Canada.[11] The term sheet includes “best-price guarantee” PTX-COVID19-B.[13] According to a provincial statement released by the Manitoba government, pending approval of the vaccine, the actual manufacturing would take place in Winnipeg by Emergent BioSolutions.[11] Pallister said that, “Building a secure, made-in-Canada vaccine supply will put Canadians at the head of the line to get a COVID vaccine, where we belong.”[11] The down payment would be 20% with a subsequent 40% to be paid when the vaccine was approved by Health Canada; the balance would be paid on delivery of the doses.[13] Specifics about the contract were released in April 2021: the total cost was estimated as CAD $36 million and the agreement included a clause for a non-refundable advance payment of CAD $7.2 million.[2] Sorenson made this comment to Global News: “Under no circumstances is Manitoba going to be on the hook for $7.2 million unless they get real value out of it”.
Federal funding
Canada’s National Research Council (NRC) provided Providence Therapeutics with CAD $5 million for the launch of January 2021 first phase of PTX-COVID19-B clinical trials.[2]
As part of the federal government’s “next generation manufacturing supercluster” program, Providence and Northern mRNA had also been “cleared to access up to $5 million” towards the manufacturing start up process, according to a federal government spokesperson.[2]
The CBC report in late April 2021 also stated that “it could be eligible for a slice of $113 million in additional funding from the National Research Council of Canada Industrial Research Assistance Program”. The federal government had provided funding to some other companies in Canada that were also working to develop a COVID-19 vaccine.[2]
Sorenson as Providence Therapeutics CEO posted an open letter to Prime Minister Justin Trudeau, in which he requested $CDN 150 million upfront to be used to pay for clinical trial and material costs.[16][9]
On 29 April 2021, Sorenson appeared before the House of Commons standing committee on international trade, to ask the Minister of Procurement, Anita Anand, to consider PTX-COVID19-B as an alternative to Moderna and Pfizer for the “2022 booster vaccines”.[15] Sorenson said that the NRC had approached Providence Therapeutics in 2020 after the company had announced their Phase I trial PTX-COVID19-B. Sorenson told the Standing Committee that, “We’ve had really good dialogue ever since phase I started. That process has gone on. That started probably [in February], as we geared up to conclude our phase I trial and release data. Although the NRC is capped at $10 million, which is certainly not sufficient to carry out phase II and phase III trials, the NRC has, through the bureaucracy, elevated us back up to the strategic innovation fund. That occurred about three weeks ago. We’re now working with the strategic innovation fund.”[15]:7
He later said that no reply had been received from the government.[17]
In a meeting with the federal COVID-19 vaccine task force and Sorenson, task force members expressed concerns that “Providence might not be able to scale up production fast enough”.[2]
Clinical trials
PTX-COVID19-B, an mRNA Humoral Vaccine, is Intended for Prevention of COVID-19 in a General Population. This Study is Designed to Evaluate Safety, Tolerability, and Immunogenicity of PTX-COVID19-B Vaccine in Healthy Seronegative Adults Aged 18-64… https://clinicaltrials.gov/ct2/show/NCT04765436
Biological E., will run a clinical trial of Providence’s vaccine in India and seek emergency use approval for it, the company said in a statement
Hyderabad-based Biological E said on Tuesday it has entered into a licensing agreement with Providence Therapeutics Holdings to manufacture the Canadian company’s mRNA COVID-19 vaccine in India.
Biological E., which also has a separate deal to produce about 600 million doses of Johnson & Johnson’s COVID-19 shot annually, will run a clinical trial of Providence’s vaccine in India and seek emergency use approval for it, the company said in a statement.
Providence will sell up to 30 million doses of its mRNA vaccine, PTX-COVID19-B, to Biological E, and will also provide the necessary technology transfer of the shot, with a minimum production capacity of 600 million doses in 2022 and a target capacity of 1 billion doses.
Financial details of the transaction were not disclosed.
India has been struggling with a devastating second wave of the pandemic and has managed to fully vaccinate only about 3% of its population. On Monday, the Serum Institute of India said it will increase production of AstraZeneca’s shot by nearly 40% in June, a step towards bridging the shortfall in the country.
“The mRNA platform has emerged as the front runner in delivering the first vaccines for emergency use to combat the COVID-19 pandemic,” said Mahima Datla, Biological E.’s managing director.
Messenger ribonucleic acid (mRNA) vaccines prompt the body to make a protein that is part of the virus, triggering an immune response. US companies Pfizer and Moderna use mRNA technology in their COVID-19 shots.
The drug regulator has approved clinical trials of another mRNA vaccine developed by local firm Gennova Biopharmaceuticals, and the government has said it will fund the studies.
Providence Therapeutics Announces Very Favorable Interim Phase 1 Trial Data for PTX-COVID19-B, its mRNA Vaccine Against COVID-19
CALGARY, AB, May 12, 2021 / – Providence Therapeutics Holdings Inc. (“Providence”) announced today very favorable interim clinical data of PTX-COVID19-B, its vaccine candidate against SARS-CoV-2 (“COVID-19”), from its Phase 1 study entitled “PRO-CL-001, A Phase 1, First-in-Human, Observer-Blinded, Randomized, Placebo Controlled, Ascending Dose Study to Evaluate the Safety, Tolerability, and Immunogenicity of PTX-COVID19-B Vaccine in Healthy Seronegative Adults Aged 18-64” (the “Phase 1 Study”), which found that PTX-COVID19-B met Providence’s target results for safety, tolerability, and immunogenicity in the participants of the Phase 1 Study.
Highlights from Providence Therapeutics’ “Phase 1 Study”:
PTX-COVID19-B was generally safe and well tolerated
PTX-COVID19-B exhibited strong virus neutralization capability across the 16µg, 40µg and 100µg dose cohorts
PTX-COVID19-B 40µg dose was selected for Phase 2 study
PTX-COVID19-B will be evaluated in additional Phase 1 population cohorts
The Phase 1 Study was designed with dose-escalations and was performed in seronegative adult subjects without evidence of recent exposure to COVID-19. The subjects were randomized to receive either the PTX-COVID19-B vaccine or a placebo in a 3:1 ratio. A total of 60 subjects participated in the Phase 1 Study.
The overall results of the Phase 1 Study are that PTX-COVID19-B was safe and well tolerated at the three dose levels of 16µg, 40µg and 100µg. Adverse events identified in the Phase 1 Study were generally mild to moderate in severity, self-resolving and transient. There were no serious adverse events reported in the Phase 1 Study. The most common adverse event reported in the Phase 1 Study was redness and pain at the injection site. Systemic reactions reported in the Phase 1 Study were generally mild to moderate and well tolerated with headache being the most common reaction reported. The reported adverse events of the Phase 1 Study were in line with the expectations of management of Providence as they compare very favorably to the adverse events data published on other mRNA vaccines for COVID-19 that have been approved for use by various health authorities around the world.
Based on the results of the Phase 1 Study, Providence intends to use a 40µg dose for the Phase 2 study of PTX-COVID19-B that is anticipated to be initiated in June 2021. Additional Phase 1 studies in adolescent and elderly populations are also planned to be undertaken by Providence.
PTX-COVID19-B vaccination induced high anti-S IgG antibodies:
Participants in the Phase 1 Study were vaccinated on day zero and day twenty-eight. Plasma samples were collected on day 1, day 8, day 28 (prior to the participant receiving the second dose), and day 42 to determine levels of IgG anti-S protein using electrochemiluminescence (“ECL”) assays from Meso Scale Discovery (“MSD”). Study participants in all three vaccine dose cohorts of the Phase 1 Study developed a strong IgG antibody response against Spike protein that was detected by day 28 and enhanced by day 42. No antibodies against S protein were detected in participants in the Phase 1 Study injected with placebo. The highest levels of antibodies were found in the 40 and 100 µg doses. By day 42, PTX-COVID19-B vaccinated participants had more than one log higher antibody levels than convalescent subjects-plasma (indicated in the dotted line) which was evaluated in the same assay.
Based on the interim data of the Phase 1 Study, the level of antibodies produced in participants by PTX-COVID19-B compare favorably to the levels of antibodies produced by other mRNA vaccines that have been approved for use against COVID-19 based on the recently published report from Stanford University, where IgG responses in individuals vaccinated with the COVID-19 mRNA vaccine compared to COVID-19 infected patients were evaluated[1].
PTX-COVID19-B vaccination induced high neutralizing antibody levels:
Neutralizing activity from the Phase 1 Study participants’ plasma was evaluated by S-ACE2 MSD assay. The results indicate that the antibodies block the interaction between S protein with the ACE2 receptor and the decrease in ECL signal is used to calculate percentage inhibition of the plasma at the same dilution. All participants in the Phase 1 Study from the 16, 40 and 100 µg dose levels showed blocking activity by day 28 and all of them reached 100% blocking activity by day 42 with samples diluted 1:100 or greater. Moreover, the quantification of the antibody levels in ng/mL with a reference standard showed that all participants in the Phase 1 Study produced neutralizing antibodies by day 28 with the first immunization and increase ten-fold by day 42, two weeks after the administration of the second dose. These results indicate that PTX-COVID19-B induced a strong neutralizing antibody response which compares very favorably to the published results of other mRNA vaccines. Further studies are being conducted by Providence to determine neutralization activity using a pseudo-virus assay.
Providence intends to advance a Phase 2 clinical trial in early June 2021, with multiple trial sites in Canada. The Phase 2 clinical trial is anticipated to be structured as a comparator trial using Pfizer/BioNTech vaccine as the positive control.
About Providence Therapeutics
Providence is a leading Canadian clinical stage biotechnology company pioneering mRNA therapeutics and vaccines with operations in Calgary, Alberta and Toronto, Ontario. In response to a worldwide need for a COVID-19 vaccine, Providence expanded its focus beyond oncology therapies and devoted its energy and resources to develop a world-class mRNA vaccine for COVID-19. Providence is focused on serving the needs of Canada, and other countries that may be underserved by large pharmaceutical programs. For more information, please visit providencetherapeutics.com.
^ Clinical trial number NCT04765436 for “PTX-COVID19-B, an mRNA Humoral Vaccine, is Intended for Prevention of COVID-19 in a General Population. This Study is Designed to Evaluate Safety, Tolerability, and Immunogenicity of PTX-COVID19-B Vaccine in Healthy Seronegative Adults Aged 18-64” at ClinicalTrials.gov
Today, the U.S. Food and Drug Administration issued an emergency use authorization (EUA) for casirivimab and imdevimab to be administered together for the treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age or older weighing at least 40 kilograms [about 88 pounds]) with positive results of direct SARS-CoV-2 viral testing and who are at high risk for progressing to severe COVID-19. This includes those who are 65 years of age or older or who have certain chronic medical conditions.
In a clinical trial of patients with COVID-19, casirivimab and imdevimab, administered together, were shown to reduce COVID-19-related hospitalization or emergency room visits in patients at high risk for disease progression within 28 days after treatment when compared to placebo. The safety and effectiveness of this investigational therapy for use in the treatment of COVID-19 continues to be evaluated.
Casirivimab and imdevimab must be administered together by intravenous (IV) infusion.
Casirivimab and imdevimab are not authorized for patients who are hospitalized due to COVID-19 or require oxygen therapy due to COVID-19. A benefit of casirivimab and imdevimab treatment has not been shown in patients hospitalized due to COVID-19. Monoclonal antibodies, such as casirivimab and imdevimab, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation.
“The FDA remains committed to advancing the nation’s public health during this unprecedented pandemic. Authorizing these monoclonal antibody therapies may help outpatients avoid hospitalization and alleviate the burden on our health care system,” said FDA Commissioner Stephen M. Hahn, M.D. “As part of our Coronavirus Treatment Acceleration Program, the FDA uses every possible pathway to make new treatments available to patients as quickly as possible while continuing to study the safety and effectiveness of these treatments.”
Monoclonal antibodies are laboratory-made proteins that mimic the immune system’s ability to fight off harmful pathogens such as viruses. Casirivimab and imdevimab are monoclonal antibodies that are specifically directed against the spike protein of SARS-CoV-2, designed to block the virus’ attachment and entry into human cells.
“The emergency authorization of these monoclonal antibodies administered together offers health care providers another tool in combating the pandemic,” said Patrizia Cavazzoni, M.D., acting director of the FDA’s Center for Drug Evaluation and Research. “We will continue to facilitate the development, evaluation and availability of COVID-19 therapies.”
The issuance of an EUA is different than an FDA approval. In determining whether to issue an EUA, the FDA evaluates the totality of available scientific evidence and carefully balances any known or potential risks with any known or potential benefits of the product for use during an emergency. Based on the FDA’s review of the totality of the scientific evidence available, the agency has determined that it is reasonable to believe that casirivimab and imdevimab administered together may be effective in treating patients with mild or moderate COVID-19. When used to treat COVID-19 for the authorized population, the known and potential benefits of these antibodies outweigh the known and potential risks. There are no adequate, approved and available alternative treatments to casirivimab and imdevimab administered together for the authorized population.
The data supporting this EUA for casirivimab and imdevimab are based on a randomized, double-blind, placebo-controlled clinical trial in 799 non-hospitalized adults with mild to moderate COVID-19 symptoms. Of these patients, 266 received a single intravenous infusion of 2,400 milligrams casirivimab and imdevimab (1,200 mg of each), 267 received 8,000 mg casirivimab and imdevimab (4,000 mg of each), and 266 received a placebo, within three days of obtaining a positive SARS-CoV-2 viral test.
The prespecified primary endpoint for the trial was time-weighted average change in viral load from baseline. Viral load reduction in patients treated with casirivimab and imdevimab was larger than in patients treated with placebo at day seven. However, the most important evidence that casirivimab and imdevimab administered together may be effective came from the predefined secondary endpoint of medically attended visits related to COVID-19, particularly hospitalizations and emergency room visits within 28 days after treatment. For patients at high risk for disease progression, hospitalizations and emergency room visits occurred in 3% of casirivimab and imdevimab-treated patients on average compared to 9% in placebo-treated patients. The effects on viral load, reduction in hospitalizations and ER visits were similar in patients receiving either of the two casirivimab and imdevimab doses.
Under the EUA, fact sheets that provide important information about using casirivimab and imdevimab administered together in treating COVID-19 as authorized must be made available to health care providers and to patients and caregivers. These fact sheets include dosing instructions, potential side effects and drug interactions. Possible side effects of casirivimab and imdevimab include: anaphylaxis and infusion-related reactions, fever, chills, hives, itching and flushing.
The EUA was issued to Regeneron Pharmaceuticals Inc.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
In a clinical trial of people with COVID-19, casirivimab and imdevimab, administered together, were shown to reduce COVID-19-related hospitalization or emergency room visits in people at high risk for disease progression within 28 days after treatment when compared to placebo.[2] The safety and effectiveness of this investigational therapy for use in the treatment of COVID-19 continues to be evaluated.[2]
The data supporting the emergency use authorization (EUA) for casirivimab and imdevimab are based on a randomized, double-blind, placebo-controlled clinical trial in 799 non-hospitalized adults with mild to moderate COVID-19 symptoms.[2] Of these participants, 266 received a single intravenous infusion of 2,400 milligrams casirivimab and imdevimab (1,200 mg of each), 267 received 8,000 mg casirivimab and imdevimab (4,000 mg of each), and 266 received a placebo, within three days of obtaining a positive SARS-CoV-2 viral test.[2]
The prespecified primary endpoint for the trial was time-weighted average change in viral load from baseline.[2] Viral load reduction in participants treated with casirivimab and imdevimab was larger than in participants treated with placebo at day seven.[2] However, the most important evidence that casirivimab and imdevimab administered together may be effective came from the predefined secondary endpoint of medically attended visits related to COVID-19, particularly hospitalizations and emergency room visits within 28 days after treatment.[2] For participants at high risk for disease progression, hospitalizations and emergency room visits occurred in 3% of casirivimab and imdevimab-treated participants on average compared to 9% in placebo-treated participants.[2] The effects on viral load, reduction in hospitalizations and ER visits were similar in participants receiving either of the two casirivimab and imdevimab doses.[2]
As of September 2020, REGEN-COV is being evaluated as part of the RECOVERY Trial.[8]
On 12 April 2021, Roche and Regeneron announced that the Phase III clinical trial REGN-COV 2069 met both primary and secondary endpoints, reducing risk of infection by 81% for the non-infected patients, and reducing time-to-resolution of symptoms for symptomatic patients to one week vs. three weeks in the placebo group.[9]
Authorization
On 21 November 2020, the U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for casirivimab and imdevimab to be administered together for the treatment of mild to moderate COVID-19 in people twelve years of age or older weighing at least 40 kilograms (88 lb) with positive results of direct SARS-CoV-2 viral testing and who are at high risk for progressing to severe COVID-19.[2][10][11] This includes those who are 65 years of age or older or who have certain chronic medical conditions.[2] Casirivimab and imdevimab must be administered together by intravenous (IV) infusion.[2]
Casirivimab and imdevimab are not authorized for people who are hospitalized due to COVID-19 or require oxygen therapy due to COVID-19.[2] A benefit of casirivimab and imdevimab treatment has not been shown in people hospitalized due to COVID-19.[2] Monoclonal antibodies, such as casirivimab and imdevimab, may be associated with worse clinical outcomes when administered to hospitalized people with COVID-19 requiring high flow oxygen or mechanical ventilation.[2]
The EUA was issued to Regeneron Pharmaceuticals Inc.[2][10][12]
On 1 February 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) started a rolling review of data on the REGN‑COV2 antibody combination (casirivimab/imdevimab), which is being co-developed by Regeneron Pharmaceuticals, Inc. and F. Hoffman-La Roche, Ltd (Roche) for the treatment and prevention of COVID‑19.[13][14] In February 2021, the CHMP concluded that the combination, also known as REGN-COV2, can be used for the treatment of confirmed COVID-19 in people who do not require supplemental oxygen and who are at high risk of progressing to severe COVID-19.[15]
The Central Drugs Standards Control Organisation (CDSCO) in India, on 5 May 2021, granted an Emergency Use Authorisation to Roche (Genentech)[16] and Regeneron[17] for use of the casirivimab/imdevimab cocktail in the country. The announcement came in light of the second wave of the COVID-19 pandemic in India. Roche India maintains partnership with Cipla, thereby permitting the latter to market the drug in the country.[18]
Deployment
Although Regeneron is headquartered in Tarrytown, New York (near New York City), REGEN-COV is manufactured at the company’s primary U.S. manufacturing facility in Rensselaer, New York (near the state capital at Albany).[19] In September 2020, to free up manufacturing capacity for REGEN-COV, Regeneron began to shift production of its existing products from Rensselaer to the Irish city of Limerick.[20]
Regeneron has a deal in place with Roche (Genentech)[21]to manufacture and market REGEN-COV outside the United States.[10][22]
On 2 October 2020, Regeneron Pharmaceuticals announced that US President Donald Trump had received “a single 8 gram dose of REGN-COV2” after testing positive for SARS-CoV-2.[23][24] The drug was provided by the company in response to a “compassionate use” (temporary authorization for use) request from the president’s physicians.[23]
ZyCoV-D is a genetically engineered DNA plasmid based vaccine encoding for the membrane proteins of the virus. The clinical trials to study the immunogenicity, and safety of the vaccine, will administer three doses at an interval of 28 days in 1048 individuals.
The ZYCOV-D vaccine candidate was developed by Cadila Healthcare Ltd. based in India1. The vaccine was developed using a DNA vaccine platform with a non-replicating and non-integrating plasmid carrying the gene of interest3. Once the plasmid DNA is introduced into host cells and the viral protein is translated, it elicits a strong immune response, stimulating the humoral and cellular components of the immune system3. The DNA vaccine platform offers minimal biosafety requirements, more improved vaccine stability, and lower cold chain requirements3. Phase I clinical trials of this vaccine candidate were completed in July 2020, with the company reporting successful dosing and tolerance1,2. As of August, 2020 the candidate is in Phase II clinical trials1.
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Clinical research
Phase I and II trials
In February 2020, Cadila Healthcare decided to develop a DNA plasmid based COVID-19 vaccine at their Vaccine Technology Centre (VTC) in Ahmedabad.[1] The vaccine candidate was able to pass the pre-clinical trials on animal models successfully. A report of the study was made available via bioRxiv.[2] Thereafter, human trials for Phase I and II were approved by the regulator.[3]
The Phase II trials of the vaccine candidate were conducted in over 1,000 volunteers as part of the adaptive Phase I/II multi-centric, dose escalation, randomised, double-blind placebo controlled method.[4][5]
Phase III trials
In November 2020, the company announced it would test the vaccine candidate on 30,000 patients in Phase III trials.[6] The vaccine would be given out in three doses at five sites across four cities of India.[7] In January 2021, the Drugs Controller General of India (DCGI) granted permission to conduct the Phase III clinical trials for 28,216 Indian participants.[8][9]
In April 2021, the company reported that they expected to have initial data for the Phase III trials by May 2021.[10]
Production
On 23 April 2021, production of the ZyCoV-D vaccine was started, with a yearly capacity of 240 million doses. It is expected to get emergency use authorization in May or June.[11]
^ Dey A, Rajanathan C, Chandra H, Pericherla HP, Kumar S, Choonia HS, et al. (26 January 2021). “Immunogenic Potential of DNA Vaccine candidate, ZyCoV-D against SARS-CoV-2 in Animal Models”. bioRxiv: 2021.01.26.428240. doi:10.1101/2021.01.26.428240. S2CID231777527.
In an exclusive interview with India Today TV, Managing Director of Zydus Cadila Dr Sharvil Patel said the company’s Covid vaccine candidate ZyCoV-D against the Covid-19 infection is very close to getting approved in India. They are likely to apply for emergency use authorisation this month.
Ahmedabad-based pharmaceutical company Zydus Cadila is likely to submit the application for emergency use authorisation of its Covid-19 vaccine candidate ‘ZyCoV-D’ in India this month. The company is confident that the vaccine will be approved in May itself. The company plants to produce one crore doses of its ‘painless’ Covid-19 vaccine per month.
If approved, ZyCoV-D will be the fourth vaccine to be used in India’s Covid-19 vaccination drive. Made in India, the company plans to ramp up the vaccine’s production to 3-4 crore doses per month and is already in talks with two other manufacturing companies for the same
Although the vaccine should ideally be stored between 2 and 8 degrees Celsius, it remains stable even at room temperature conditions at 25 degrees Celsius. It is easy to administer, the developers said, and will be administered via intradermal injection.
If approved for emergency use, ZyCoV-D could help India fill the vacuum of vaccine doses currently being experienced in the country’s immunisation drive.
In an exclusive interview with India Today TV, Sharvil Patel sheds details on all aspects of the Covid-19 vaccine ZyCoV-D.
When asked the status of Covid vaccine candidate ZyCoV-D and when exactly Zydus Cadila would apply for emergency use authorisation in India, Dr Sharvil Patel said the vaccine was getting very close to getting approved in the country.
“I am very happy to say that India’s first indigenously developed DNA vaccine candidate against Covid, which is our ZyCoV-D, is getting very close to approval,” he said.
“We have almost completed all our recruitment for the clinical trials. We have, by far, recruited the largest number of patients for a Covid vaccine trial in India. The number of volunteers who have been vaccinated as a part of the trial is 28,000,” Sharvil Patel said.
Sharvil Patel also said that his company has also included children in the 12-17 age group for the vaccine trials.
He said, “The recruitment holds very important milestones in terms of cohorts because not only have we included the elderly and those with co-morbidities, but also children in the age group of 12 to 17 years.”
Sharvil Patel said as soon as the efficacy data is obtained, Sydus Cadila will file for emergency use authorisation. As soon as the approval is granted, Zydus Cadila will start production of Covid-19 vaccines from July, he said.
“We hope to see our efficacy data in the middle of May. As soon as we see strong efficacy which correlates to the vaccine’s strong immunogenicity in Phase 2, we will file for emergency use authorization. We hope to produce a good quantity of the vaccine from July onwards to make sure it is available to the people. That is the need of the hour right now,” Sharvil Patel said.
He said by May the company will be in a position to talk to the regulators about the restricted use of the Covid-19 vaccine. “The regulatory process is a rolling one. I believe the regulators look at the data in a short period of time,” Sharvil Patel said.
“We have submitted a lot of data already so that it will aid the regulators once we provide them with the efficacy results. We are, hence, expecting to get the approval in May itself,” Sharvil Patel said.
Gam-COVID-Vac was created by Gamaleya Research Institute of Epidemiology and MIcrobiology in Russia. The vaccine candidate is a heterologous COVID-19 vaccine containing two components, recombinant adenovirus type 26 (rAd26) vector and recombinant adenovirus type 5 (rAd5) vector which both carry the SARS-CoV-2 spike glycoprotein. The vaccine is offered in both a frozen (Gam-COVID-Vac) and freeze-dried formulation (lyophilizate; Gam-COVID-Vac Lyo). Phase 1/2 human trials with 76 participants evaluated the safety, tolerability, and immunogenicity of both frozen (Gam-COVID-Vac;NCT04436471) and freeze-dried (Gam-COVID-Vac Lyo;NCT04437875) vaccine candidates in June 2020, and were completed in early August 2020. Preliminary results suggested that all participants developed antibodies to the SARS-CoV-2 glycoproteins with a good safety profile in both trials.
Gam-COVID-Vac was initially approved for distribution in Russia on the preliminary results of Phase I–II studies eventually published on 4 September 2020.[5] The quick approval in early August of Gam-COVID-Vac was met with criticism in mass media and precipitated discussions in the scientific community whether this decision was justified in the absence of robust scientific research confirming the safety and efficacy of the vaccine.[2][3][6][7][8] On 2 February 2021, an interim analysis from the trial was published in The Lancet, indicating 91.6% efficacy without unusual side effects.[9]
Emergency mass-distribution of the vaccine began in December 2020 in multiple countries including Russia, Argentina, Belarus, Hungary, Serbia and the United Arab Emirates. As of February 2021, over a billion doses of the vaccine were ordered for immediate distribution globally.[10]
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President Putin‘s meeting with government members, on 11 August 2020 via videoconference, at which he announced a conditionally registered vaccine against COVID-19.[2][3] Medical worker in Moscow with the vaccineSee also: COVID-19 vaccine
The recombinantadenovirus types 26 and 5 are both used as vectors in the vaccine. They were biotechnology-derived and contain the SARS-CoV-2 S protein cDNA. Both of them are administered into the deltoid muscle: the Ad26-based vaccine is used on the first day and the Ad5 vaccine is used on the 21st day to boost immune response.[11][14][15]
The vaccine can be formulated as frozen (storage temperature must be −18 °C or 0 °F or lower) and freeze-dried (“Gam-COVID-Vac-Lyo”, storage temperature is 2–8 °C or 36–46 °F) dosage forms.[16] The first formulation was developed for large-scale use, it is cheaper and easier to manufacture. The production of a lyophilized formulation takes much more time and resources, although it is more convenient for storage and transportation. Gam-COVID-Vac-Lyo was developed especially for vaccine delivery to hard-to-reach regions of Russia.[17] The head of the Gamaleya Research Institute Alexander Ginzburg estimates that it will take 9–12 months to vaccinate the vast majority of the Russian population, assuming in-country resources are adequate.[18][19] A single-dose version is also being developed to speed up vaccination outside Russia. It will offer less protection than the two-dose versions, but it is still expected to reach an efficacy of 85%.[20][21]
Clinical research
Phase I–II
A phase I safety trial began on 18 June.[2] On 4 September, data on 76 participants in a phase I–II trial were published, indicating preliminary evidence of safety and an immune response.[5] The results were challenged by international vaccine scientists as being incomplete, suspicious, and unreliable when identical data were reported for many of the trial participants,[22] but the authors responded that there was a small sample size of nine, and the measured results of titration could only take discrete values (800, 1600, 3200, 6400). Coupled with the observation that values tended to reach a plateau after three to four weeks, they contend that it is not unlikely that several participants would show identical results for days 21 to 28.[23]
Phase III
Sputnik V, efficacy for different conditions. The error bars indicate the confidence interval containing the efficacy with 95% probability
In early November 2020, Israel Hadassah Medical Center director-general Prof. Zeev Rotstein stated that Hadassah’s branch in Moscow’s Skolkovo Innovation Center was collaborating on a phase III clinical trial.[24]
On 2 February 2021, an interim analysis from the Moscow trial was published in The Lancet, indicating 91.6% efficacy (95% CI 85.6–95.2) after the second vaccination, without unusual side effects.[30] The trial started on 7 September 2020 using the frozen liquid form of the vaccine, and data was analysed up to the second database lock on 24 November 2020. The over-60-years-old group in the trial (oldest participant was 87) had essentially the same efficacy (91.8%) as for all ages. The lowest age participants were 18 years old.[9][31]
Sputnik–AstraZeneca COVID-19 vaccine trials
On 21 December 2020 the Russian Direct Investment Fund (RDIF), the Gamaleya National Center, AstraZeneca and R-Pharm have signed an agreement aimed at the development and implementation of a clinical research program to assess the immunogenicity and safety of the combined use of one of the components of the Sputnik V vaccine developed by the Gamaleya Center, and one of the components of the AZD1222 vaccine, developed by AstraZeneca and the University of Oxford.[32] The study program will last 6 months in several countries, and it is planned to involve 100 volunteers in each study program. On 9 February 2021, the Ministry of Health of the Republic of Azerbaijan allowed clinical studies in the country for the combined use of the Sputnik V vaccine and the vaccine developed by AstraZeneca, stating that the trials would begin before the end of February 2021.[33][34]
Composition
The Gam-COVID-Vac is a two-vector vaccine.[1] The active component for both vectors is a modified (recombinant) replication-defective adenovirus of a different serotype (Serotype 26 for the first vaccination and serotype 5 for the second vaccination), which has been modified to include the protein S-expressing gene of SARS-CoV-2.[1]
The other ingredients (excipients) are the same, both quantitatively and qualitatively, in the two components.[35]
During preclinical and clinical trials, 38 participants who received one or two doses of the Gam-COVID-Vac vaccine had produced antibodies against SARS-CoV-2’s spike protein, including potent neutralizing antibodies that inactivate viral particles.[2] On 11 August 2020, the Russian minister of HealthMikhail Murashko announced at a government briefing with the participation of President Vladimir Putin regulatory approval of the vaccine for widespread use. The state registration of the vaccine was carried out “conditionally” with post-marketing measures according to the decree of the Government of the Russian Federation. The registration certificate for the vaccine stated that it could not be used widely in Russia until 1 January 2021, and before that, it may be provided to “a small number of citizens from vulnerable groups”, such as medical staff and the elderly, according to a Ministry of Health spokesperson.[3] The license under register number No. ЛП-006395 (LP-006395) was issued on 11 August by the Russian Ministry of Health. Although the announcement was made even before the vaccine candidate had been entered into Phase III trials, the practice of marketing authorization “on conditions” also exists in other countries.[39][40] On 26 August, certificate No. ЛП-006423 (LP-006423) was issued for the lyophilized formulation “Gam-COVID-Vac-Lyo”.[2][3][7][41][5]
The commercial release of the Gam-COVID-Vac was first scheduled for September 2020. In October, Mikhail Murashko said that the Gam-COVID-Vac will be free for all Russian citizens after the launching of mass production.[42][43] Later on, Russian Ministry of Health registered maximum ex-factory price equal to 1,942 rubles for two components and included them into The National List of Essential medicines.[44] There were also suggestions to include the vaccine in the National Immunisation Calendar of Russia.[44]
According to Russian media, the mass production of the Gam-COVID-Vac was launched by 15 August. By that moment, the Russian Federation has already received applications from 20 countries for the supply of 1 billion doses of vaccine. Three facilities were able to produce about a million doses per month at each with a potential doubling of capacity by winter. By the end of 2020, Gamaleya Research Institute’s production, according to an interview with the organization’s spokesperson, was planned to produce 3–5 million doses.[45][46]
On 9 March 2021, an agreement was signed by the RDIF sovereign wealth fund and Swiss-based pharmaceutical company Adienne to produce the vaccine in Italy. Kirill Dmitriev, RDIF’s head, told Russian state TV his fund had also struck deals with production facilities in Spain, France and Germany for local manufacturing of the vaccine.[47]
On 11 August 2020, a World Health Organization (WHO) spokesperson said, “… prequalification of any vaccine includes the rigorous review and assessment of all required safety and efficacy data”.[8]
A WHO assistant director said, “You cannot use a vaccine or drugs or medicines without following through all of these stages, having complied with all of these stages”.[49]
Francois Balloux, a geneticist at University College London, called the Russian government’s approval of Gam-COVID-Vac a “reckless and foolish decision”.[2] Professor Paul Offit, the director of the Vaccine Education Center at Children’s Hospital of Philadelphia, characterized the announcement was a “political stunt”, and stated that the untested vaccine could be very harmful.[8]
Stephen Griffin, Associate Professor in the School of Medicine, University of Leeds, said “that we can be cautiously optimistic that SARS-CoV2 vaccines targeting the spike protein are effective.” Moreover, as the Sputnik antigen is delivered via a different modality, namely using a disabled Adenovirus rather than formulated RNA, this provides flexibility in terms of perhaps one or other method providing better responses in certain age-groups, ethnicities, etc., plus the storage of this vaccine ought to be more straightforward.[50][failed verification][51]
Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, said “the data [is] compatible with the vaccine being reasonably effective … These results are consistent with what we see with other vaccines, because the really big message for global health scientists is that this disease [COVID-19] is able to be addressed by vaccines.”[50]
Julian Tang, clinical virologist at the University of Leicester, said: “Despite the earlier misgivings about the way this Russian Sputnik V vaccine was rolled out more widely – ahead of sufficient Phase 3 trial data – this approach has been justified to some extent now.”[52]
Ian Jones, a professor of virology at the University of Reading, and Polly Roy, professor and Chair of Virology at The London School of Hygiene and Tropical Medicine, commenting on phase III results published in the Lancet in February 2021, said “The development of the Sputnik V vaccine has been criticised for unseemly haste, corner cutting, and an absence of transparency. But the outcome reported here is clear and the scientific principle of vaccination is demonstrated, which means another vaccine can now join the fight to reduce the incidence of COVID-19.”[53]
Hildegund C. J. Ertl, a vaccine scientist at the Wistar Institute, called the phase-III results published on 2 February 2021 “great”: “Good safety profile, more than 90% efficacy across all age groups, 100% efficacy against severe disease or death, can be stored in the fridge and low cost. What more would we want?”[54]
An opinion poll of Canadians conducted by Léger in August 2020 found that a majority (68%) would not take the Russian vaccine if offered a free dose, compared to 14% who said they would take it. When Americans were asked the same question, 59% would not take the Russian vaccine if offered a free dose, compared to 24% who said they would take it.[58][59]
At that time, British and American officials stated that the Gam-COVID-Vac vaccine would likely be rejected due to concerns that the normally rigorous process of vaccine clinical testing was not followed.[60] One public health expert said the quick approval of Gam-COVID-Vac by the Russian government was “cutting corners”, and may harm public confidence if the vaccine proves to be unsafe or ineffective.[7] “There is a huge risk that confidence in vaccines would be damaged by a vaccine that received approval and was then shown to be harmful”, said immunologistPeter Openshaw.[7]
As for early September 2020, according to public opinion polls, only half of the Russian population would take the vaccine voluntarily.[61]
In Russia
Vaccination of military personnel and civilian specialists of the Northern Fleet with the second component of the drug “Gam-COVID-Vac” (“Sputnik V”).
In the beginning of December 2020, Russian authorities announced the start of a large-scale free of charge vaccination with Gam-COVID-Vac for Russian citizens: the “immunization” program was launched on 5 December 2020 (with 70 Moscow-based medical centers providing vaccinations).[62]
Doctors and other medical workers, teachers, and social workers were given priority due to their highest risk of exposure to the disease.[63] The age for those receiving shots was initially capped at 60, later this restriction was lifted.[64]
Potential recipients were notified via text messaging, which says “You are working at an educational institution and have top-priority for the COVID-19 vaccine, free of charge”. Patients are asked a few general health questions before getting the vaccine. Program’s leaflet is handed to the patient, which warns of possible side effects, suggesting those are most likely to be mild and last a couple of days at most.[65][66][67] People with certain underlying health conditions, pregnant women, and those who have had a respiratory illness for the past two weeks are barred from vaccination.[63] Vaccine vial is removed from medical centre’s freezer about 15 minutes before use.
In early December 2020, the Minister of Health, Mikhail Murashko, said that Russia had already vaccinated more than 100,000 high-risk people.[68] Forty thousand of those are volunteers in Sputnik V’s Phase 3 trials, another 60,000 medics and doctors have also taken the vaccine.[69] The head of the Russian Direct Investment Fund, Kirill Dmitriev, said in an interview with the BBC that Russian medics expect to give about 2 million people coronavirus vaccinations in December.[70]
Up to the beginning of December 2020, Generium (which is supervised by Pharmstandard) and Binnopharm (which is supervised by AFK Sistema) companies produced Gam-COVID-Vac on a large scale.
On 10 December, Deputy Prime MinisterTatyana Golikova announced that approximately 6.9 million doses of the Sputnik V vaccine will enter civilian circulation in Russia before the end of February 2021.[71]Moscow MayorSergei Sobyanin announced that the newly-opened Moscow-based “R-Pharm” will become a leading manufacturer of Russia’s Sputnik V coronavirus vaccine. Working at full capacity, the factory will produce up to 10 million doses a month.[72]
Outside of Russia
In dark green are the countries that ordered (Russian or licensed domestic production; China also plans to produce Sputnik V on its territory.) or approved Sputnik V vaccine against COVID-19 (w/disputed Crimea). In light green are the countries that have shown interest in obtaining the vaccine.
According to the Russian Direct Investment Fund, they had received orders for more than 1.2 billion doses of the vaccine as of December 2020. Over 50 countries had made requests for doses, with supplies for the global market being produced by partners in India, Brazil, China, South Korea, Hungary, and other countries.[73][74] In August 2020, according to the Russian authorities, there were at least 20 countries that wanted to obtain the vaccine.[75]
While free in Russia, the cost per dose would be less than US$10 (or less than US$20 for the two doses needed to vaccinate one person) on international markets, which makes it much more affordable compared to mRNA vaccines from other manufacturers. Kirill Dmitriev, head of the fund, told reporters that over 1 billion doses of the vaccine are expected to be produced in 2021 outside of Russia.[76][77]
According to The New York Times’ sources,[79] to secure the release of an Israeli civilian held in Syria, Israel agreed to finance a supply of Russian-made Covid-19 vaccines for Damascus.
Argentina had agreed to buy 25 million doses of Russia’s Covid-19 vaccine.[80] The vaccine was registered and approved in Argentina in late December 2020.[81] The Brazilian state of Bahia has also signed an agreement to conduct Phase III clinical trials of the Sputnik V vaccine and plans to buy 50 million doses to market in northeastern Brazil.[82]
On 21 January 2021, the Argentine president Alberto Fernández became the first Latin American leader to be inoculated against the disease via the then recently approved Sputnik V.[83][84]
Due to the delay in shipping of doses from Italy and the European Union, San Marino imported doses of the Sputnik V vaccine (not approved by the E.M.A.) and started a mass vaccination on 28 February of its healthcare workers.[85]
EMA’s human medicines committee (CHMP) has started a rolling review of Sputnik V (Gam-COVID-Vac), a COVID-19 vaccine developed by Russia’s Gamaleya National Centre of Epidemiology and Microbiology. [86] Asked about the prospect of Austria taking the same step (as some other European countries chose to do), EMA management board chair Christa Wirthumer-Hoche told Austria’s ORF broadcaster: “It’s somewhat comparable to Russian roulette. I would strongly advise against a national emergency authorisation,” she said, pointing to the fact that there was not yet sufficient safety data about those who had already been given the vaccine. “We could have Sputnik V on the market in future, when we’ve examined the necessary data,” she said, adding that the vaccine needed to match up to European criteria on quality control and efficacy.[87]
Although vaccination rates in Russia are below those of other developed nations (as of March 2021),[88] Russia is pursuing deals to supply its vaccine abroad.[89]
Emergency use authorization
show Full authorizationshow Emergency authorizationshow Ordered doses Eligible COVAX recipient (assessment in progress)[143]EMA review in progress[144]
On 19 January 2021, the Russian authorities applied for the registration of Sputnik V in the European Union, according to the RDIF.[151] On 10 February, the European Medicines Agency (EMA) said that they had “not received an application for a rolling review or a marketing authorisation for the vaccine”. The developers have only expressed their interest that the vaccine be considered for a rolling review, but EMA’s Human Medicines Committee (CHMP) and the COVID-19 EMA pandemic Task Force (COVID-ETF) need to give their agreement first before developers can submit their application for initiation of the rolling review process.[152] On 4 March 2021, the Committee for Medicinal Products for Human Use (CHMP) of the EMA started a rolling review of Sputnik V.[153] The EU applicant is R-Pharm Germany GmbH.[153]
Emergency use has also been authorized in Algeria, Bolivia, Serbia, the Palestinian territories,[154] and Mexico.[155]
On 1 March 2021, Slovakia bought two million Sputnik V vaccines. Slovakia received the first batch of 200,000 vaccines, and expects to receive another 800,000 doses in March and April. Another 1 million vaccines are set to arrive in May and June.[158] The Czech Republic is also considering buying Sputnik V.[159]
On 18 March 2021, German regional leaders including State Premiers and the major of Berlin called for the swift approval of the Russian vaccine by the European Medicines Agency to counteract the acute shortages of effective vaccines in Europe. German medical experts have recommended its approval also, and consider the Sputnik Vaccine “clever” and “highly safe”.[160]
As of March 23, 2021, 56 countries have granted Sputnik V emergency use authorization.[163]
Production
As of March 2021, RDIF has licensed production in India, China, South Korea and Brazil. In the EU, RDIF has signed production agreements, subject to European Medicines Agency approval, with companies in Germany, Spain and France, and is in negotiations with a Swiss/Italian company. By the end of March 2021 RDIF anticipates 33 million doses will have been manufactured in Russia, less than 5% of which will have been exported.[164]
An agreement for the production of over 100 million doses of vaccine in India has been made with Dr. Reddy’s Laboratories, who on 11 January 2021 submitted mid-stage trial data to the Indian regulator and recommended moving onto late-stage trials.[154] The RDIF announced plans to sell 100 million doses to India, 35 million to Uzbekistan, and 32 million to Mexico, as well as 25 million each to Nepal and Egypt.[165]
In March 2021, the Italian-Russian Chamber of Commerce announced that Italy would be the first EU country to manufacture the two-dose COVID-19 vaccine under license. From July to the end of 2021, the Italian-Swiss pharmaceutical company Adienne in Caponago will manufacture 10 million doses. The announcement came in a time of acute vaccine shortages in Europe while the Sputnik V vaccine was still under review by the European Medicines Agency. Russian authorities said they would be able to provide a total of 50 million doses to European countries beginning in June 2021.[166]
The Sputnik V doses to be manufactured in South Korea are not for domestic use. The vaccine is to be exported to Russia, Algeria, Argentina, Hungary, Iran and the United Arab Emirates.[167]
^ Clinical trial number NCT04642339 for “Clinical Trial of the Immunogenicity, Safety, and Efficacy of the Gam-COVID-Vac Vaccine Against COVID-19 in Venezuela” at ClinicalTrials.gov
^ Cyr E (24 August 2020). “Leger’s Weekly Survey” (PDF). leger360.com. Archived from the original (PDF) on 5 September 2020. Retrieved 5 September 2020.
NVX-CoV2373 is a SARS-CoV-2 rS vaccine candidate and was shown to have high immunogenicity in studies. The vaccine is created from the genetic sequence of COVID-19 and the antigen derived from the virus spike protein is generated using recombinant nanoparticle technology. The vaccine was developed and tested by Novavax. As of May 2020, the company is pursuing a Phase 1 clinical trial (NCT04368988) to test the vaccine.
History
Novavax was founded in 1987. It focused principally on experimental vaccine development, but did not achieve a successful launch up to 2021.[4]
In June 2013, Novavax acquired the Matrix-M adjuvant platform with the purchase of Swedish company Isconova AB and renamed its new subsidiary Novavax AB.[5]
In March 2015 the company completed a Phase I trial for its Ebola vaccine candidate,[10] as well as a phase II study in adults for its RSV vaccine, which would become ResVax.[11] The ResVax trial was encouraging as it showed significant efficacy against RSV infection.[11]
2016 saw the company’s first phase III trial, the 12,000 adult Resolve trial,[11] for its respiratory syncytial virus vaccine, which would come to be known as ResVax, fail in September.[3] This triggered an eighty-five percent dive in the company’s stock price.[3] Phase II adult trial results also released in 2016 showed a stimulation of antigencity, but failure in efficacy.[11] Evaluation of these results suggested that an alternative dosing strategy might lead to success, leading to plans to run new phase II trials.[3] The company’s difficulties in 2016 led to a three part strategy for 2017: cost reduction through restructuring and the termination of 30% of their workforce; pouring more effort into getting ResVax to market; and beginning clinical trials on a Zika virus vaccine.[3]
Alongside the adult studies of ResVax, the vaccine was also in 2016 being tested against infant RSV infection through the route of maternal immunization.[11]
In 2019, late-stage clinical testing of ResVax, failed for a second time, which resulted in a major downturn in investor confidence and a seventy percent reduction in capital value for the firm.[12][13] As a secondary result, the company was forced to conduct a reverse stock split in order to maintain Nasdaq minimum qualification, meaning it was in risk of being delisted.[13]
The company positions NanoFlu for the unmet need for a more effective vaccine against influenza, particularly in the elderly who often experience serious and sometimes life-threatening complications. In January 2020, it was granted fast track status by the U.S. Food and Drug Administration (FDA) for NanoFlu.
In May 2020, Novavax received US$384 million from the Coalition for Epidemic Preparedness Innovations to fund early-stage evaluation in healthy adults of the company’s COVID-19 vaccine candidate NVX-CoV2373 and to develop resources in preparation for large-scale manufacturing, if the vaccine proves successful.[15] CEPI had already invested $4 million in March.[15]
Drugs in development
ResVax is a nanoparticle-based treatment using a recombinant F lipoprotein or saponin, “extracted from the Quillaja saponaria [or?] Molina bark together with cholesterol and phospholipid.”[16] It is aimed at stimulating resistance to respiratory syncytial virus infection, targeting both adult and infant populations.[11]
In January 2020, Novavax was given Fast Track status by the FDA to expedite the review process for NanoFlu, a candidate influenze vaccine undergoing a Phase III clinical trial scheduled for completion by mid-2020.[17]
In January 2020, Novavax announced development of a vaccine candidate, named NVX-CoV2373, to establish immunity to SARS-CoV-2.[18] NVX-CoV2373 is a protein subunit vaccine that contains the spike protein of the SARS-CoV-2 virus.[19] Novavax’s work is in competition for vaccine development among dozens of other companies.
In January 2021, the company released phase 3 trials showing that it has 89% efficacy against Covid-19, and also provides strong immunity against new variants.[20] It has applied for emergency use in the US and UK but will be distributed in the UK first.Novavax COVID-19 Vaccine Demonstrates 89.3% Efficacy in UK Phase 3 TrialJan 28, 2021 at 4:05 PM ESTDownload PDF
First to Demonstrate Clinical Efficacy Against COVID-19 and Both UK and South Africa Variants
Strong efficacy in Phase 3 UK trial with over 50% of cases attributable to the now-predominant UK variant and the remainder attributable to COVID-19 virus
Clinical efficacy demonstrated in Phase 2b South Africa trial with over 90% of sequenced cases attributable to prevalent South Africa escape variant
Company to host investor conference call today at 4:30pm ET
GAITHERSBURG, Md., Jan. 28, 2021 (GLOBE NEWSWIRE) — Novavax, Inc. (Nasdaq: NVAX), a biotechnology company developing next-generation vaccines for serious infectious diseases, today announced that NVX-CoV2373, its protein-based COVID-19 vaccine candidate, met the primary endpoint, with a vaccine efficacy of 89.3%, in its Phase 3 clinical trial conducted in the United Kingdom (UK). The study assessed efficacy during a period with high transmission and with a new UK variant strain of the virus emerging and circulating widely. It was conducted in partnership with the UK Government’s Vaccines Taskforce. Novavax also announced successful results of its Phase 2b study conducted in South Africa.
“With today’s results from our UK Phase 3 and South Africa Phase 2b clinical trials, we have now reported data on our COVID-19 vaccine from Phase 1, 2 and 3 trials involving over 20,000 participants. In addition, our PREVENT-19 US and Mexico clinical trial has randomized over 16,000 participants toward our enrollment goal of 30,000. NVX-CoV2373 is the first vaccine to demonstrate not only high clinical efficacy against COVID-19 but also significant clinical efficacy against both the rapidly emerging UK and South Africa variants,” said Stanley C. Erck, President and Chief Executive Officer, Novavax. “NVX-CoV2373 has the potential to play an important role in solving this global public health crisis. We look forward to continuing to work with our partners, collaborators, investigators and regulators around the world to make the vaccine available as quickly as possible.”
NVX-CoV2373 contains a full-length, prefusion spike protein made using Novavax’ recombinant nanoparticle technology and the company’s proprietary saponin-based Matrix-M™ adjuvant. The purified protein is encoded by the genetic sequence of the SARS-CoV-2 spike (S) protein and is produced in insect cells. It can neither cause COVID-19 nor can it replicate, is stable at 2°C to 8°C (refrigerated) and is shipped in a ready-to-use liquid formulation that permits distribution using existing vaccine supply chain channels.
UK Phase 3 Results: 89.3% Efficacy
The study enrolled more than 15,000 participants between 18-84 years of age, including 27% over the age of 65. The primary endpoint of the UK Phase 3 clinical trial is based on the first occurrence of PCR-confirmed symptomatic (mild, moderate or severe) COVID-19 with onset at least 7 days after the second study vaccination in serologically negative (to SARS-CoV-2) adult participants at baseline.
The first interim analysis is based on 62 cases, of which 56 cases of COVID-19 were observed in the placebo group versus 6 cases observed in the NVX-CoV2373 group, resulting in a point estimate of vaccine efficacy of 89.3% (95% CI: 75.2 – 95.4). Of the 62 cases, 61 were mild or moderate, and 1 was severe (in placebo group).
Preliminary analysis indicates that the UK variant strain that was increasingly prevalent was detected in over 50% of the PCR-confirmed symptomatic cases (32 UK variant, 24 non-variant, 6 unknown). Based on PCR performed on strains from 56 of the 62 cases, efficacy by strain was calculated to be 95.6% against the original COVID-19 strain and 85.6% against the UK variant strain [post hoc].
The interim analysis included a preliminary review of the safety database, which showed that severe, serious, and medically attended adverse events occurred at low levels and were balanced between vaccine and placebo groups.
“These are spectacular results, and we are very pleased to have helped Novavax with the development of this vaccine. The efficacy shown against the emerging variants is also extremely encouraging. This is an incredible achievement that will ensure we can protect individuals in the UK and the rest of the world from this virus,” said Clive Dix, Chair, UK Vaccine Taskforce.
Novavax expects to share further details of the UK trial results as additional data become available. Additional analysis on both trials is ongoing and will be shared via prepublication servers as well as submitted to a peer-reviewed journal for publication. The company initiated a rolling submission to the United Kingdom’s regulatory agency, the MHRA, in mid-January.
South Africa Results: Approximately 90% of COVID-19 cases attributed to South Africa escape variant
In the South Africa Phase 2b clinical trial, 60% efficacy (95% CI: 19.9 – 80.1) for the prevention of mild, moderate and severe COVID-19 disease was observed in the 94% of the study population that was HIV-negative. Twenty-nine cases were observed in the placebo group and 15 in the vaccine group. One severe case occurred in the placebo group and all other cases were mild or moderate. The clinical trial also achieved its primary efficacy endpoint in the overall trial population, including HIV-positive and HIV-negative subjects (efficacy of 49.4%; 95% CI: 6.1 – 72.8).
This study enrolled over 4,400 patients beginning in August 2020, with COVID-19 cases counted from September through mid-January. During this time, the triple mutant variant, which contains three critical mutations in the receptor binding domain (RBD) and multiple mutations outside the RBD, was widely circulating in South Africa. Preliminary sequencing data is available for 27 of 44 COVID-19 events; of these, 92.6% (25 out of 27 cases) were the South Africa escape variant.
Importantly in this trial, approximately 1/3 of the patients enrolled (but not included in the primary analyses described above) were seropositive, demonstrating prior COVID-19 infection at baseline. Based on temporal epidemiology data in the region, the pre-trial infections are thought to have been caused by the original COVID-19 strain (i.e., non-variant), while the subsequent infections during the study were largely variant virus. These data suggest that prior infection with COVID-19 may not completely protect against subsequent infection by the South Africa escape variant, however, vaccination with NVX-CoV2373 provided significant protection.
“The 60% reduced risk against COVID-19 illness in vaccinated individuals in South Africans underscores the value of this vaccine to prevent illness from the highly worrisome variant currently circulating in South Africa, and which is spreading globally. This is the first COVID-19 vaccine for which we now have objective evidence that it protects against the variant dominating in South Africa,” says Professor Shabir Maddi, Executive Director of the Vaccines and Infectious Diseases Analytics Research Unit (VIDA) at Wits, and principal investigator in the Novavax COVID-19 vaccine trial in South Africa. “I am encouraged to see that Novavax plans to immediately begin clinical development on a vaccine specifically targeted to the variant, which together with the current vaccine is likely to form the cornerstone of the fight against COVID-19.”
Novavax initiated development of new constructs against the emerging strains in early January and expects to select ideal candidates for a booster and/or combination bivalent vaccine for the new strains in the coming days. The company plans to initiate clinical testing of these new vaccines in the second quarter of this year.
“A primary benefit of our adjuvanted platform is that it uses a very small amount of antigen, enabling the rapid creation and large-scale production of combination vaccine candidates that could potentially address multiple circulating strains of COVID-19,” said Gregory M. Glenn, M.D., President of Research and Development, Novavax. “Combined with the safety profile that has been observed in our studies to-date with our COVID-19 vaccine, as well as prior studies in influenza, we are optimistic about our ability to rapidly adapt to evolving conditions.”
The Coalition for Epidemic Preparedness Innovations (CEPI) funded the manufacturing of doses of NVX-CoV2373 for this Phase 2b clinical trial, which was supported in part by a $15 million grant from the Bill & Melinda Gates Foundation.
Significant progress on PREVENT-19 Clinical Trial in US and Mexico
To date, PREVENT-19 has randomized over 16,000 participants and expects to complete our targeted enrollment of 30,000 patients in the first half of February. PREVENT-19 is being conducted with support from the U.S. government partnership formerly known as Operation Warp Speed, which includes the Department of Defense, the Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services (HHS) Office of the Assistant Secretary for Preparedness and Response, and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH) at HHS. BARDA is also providing up to $1.75 billion under a Department of Defense agreement.
PREVENT-19 (the PRE-fusion protein subunit Vaccine Efficacy Novavax Trial | COVID-19) is a Phase 3, randomized, placebo-controlled, observer-blinded study in the US and Mexico to evaluate the efficacy, safety and immunogenicity of NVX-CoV2373 with Matrix-M in up to 30,000 subjects 18 years of age and older compared with placebo. The trial design has been harmonized to align with other Phase 3 trials conducted under the auspices of Operation Warp Speed, including the use of a single external independent Data and Safety Monitoring Board to evaluate safety and conduct an unblinded review when predetermined interim analysis events are reached.
The trial’s primary endpoint is the prevention of PCR-confirmed, symptomatic COVID-19. The key secondary endpoint is the prevention of PCR-confirmed, symptomatic moderate or severe COVID-19. Both endpoints will be assessed at least seven days after the second study vaccination in volunteers who have not been previously infected with SARS-CoV-2.
Conference Call
Novavax will host a conference call today at 4:30pm ET. The dial-in numbers for the conference call are (877) 212-6076 (Domestic) or (707) 287-9331 (International), passcode 7470222. A replay of the conference call will be available starting at 7:30 p.m. ET on January 28, 2021 until 7:30 p.m. ET on February 4, 2021. To access the replay by telephone, dial (855) 859-2056 (Domestic) or (404) 537-3406 (International) and use passcode 7470222.
A webcast of the conference call can also be accessed on the Novavax website at novavax.com/events. A replay of the webcast will be available on the Novavax website until April 28, 2021.
About NVX-CoV2373
NVX-CoV2373 is a protein-based vaccine candidate engineered from the genetic sequence of SARS-CoV-2, the virus that causes COVID-19 disease. NVX-CoV2373 was created using Novavax’ recombinant nanoparticle technology to generate antigen derived from the coronavirus spike (S) protein and is adjuvanted with Novavax’ patented saponin-based Matrix-M™ to enhance the immune response and stimulate high levels of neutralizing antibodies. NVX-CoV2373 contains purified protein antigen and can neither replicate, nor can it cause COVID-19. Over 37,000 participants have participated to date across four different clinical studies in five countries. NVX-CoV2373 is currently being evaluated in two pivotal Phase 3 trials: a trial in the U.K that completed enrollment in November and the PREVENT-19 trial in the U.S. and Mexico that began in December.
About Matrix-M™
Novavax’ patented saponin-based Matrix-M™ adjuvant has demonstrated a potent and well-tolerated effect by stimulating the entry of antigen presenting cells into the injection site and enhancing antigen presentation in local lymph nodes, boosting immune response.
About Novavax
Novavax, Inc. (Nasdaq: NVAX) is a biotechnology company that promotes improved health globally through the discovery, development and commercialization of innovative vaccines to prevent serious infectious diseases. The company’s proprietary recombinant technology platform combines the power and speed of genetic engineering to efficiently produce highly immunogenic nanoparticles designed to address urgent global health needs. Novavax is conducting late-stage clinical trials for NVX-CoV2373, its vaccine candidate against SARS-CoV-2, the virus that causes COVID-19. NanoFlu™, its quadrivalent influenza nanoparticle vaccine, met all primary objectives in its pivotal Phase 3 clinical trial in older adults and will be advanced for regulatory submission. Both vaccine candidates incorporate Novavax’ proprietary saponin-based Matrix-M™ adjuvant to enhance the immune response and stimulate high levels of neutralizing antibodies.
Type: Stable, prefusion protein made using Novavax’ proprietary nanoparticle technology, and incorporating its proprietary saponin-based Matrix-M™ adjuvant.
2021 Status: Novavax on March 11 announced final efficacy of 96.4% against mild, moderate and severe disease caused by the original COVID-19 strain in a pivotal Phase III trial in the U.K. of NVX–CoV2373. The study enrolled more than 15,000 participants between 18-84 years of age, including 27% over the age of 65.
The company also announced the complete analysis of its Phase IIb trial in South Africa, showing the vaccine had an efficacy of 55.4% among a cohort of HIV-negative trial participants, and an overall efficacy of 48.6% against predominantly variant strains of SARS-CoV-2 among 147 PCR-positive cases (51 cases in the vaccine group and 96 in the placebo group). Across both trials, NVX-CoV2373 demonstrated 100% protection against severe disease, including all hospitalization and death.
Philippines officials said March 10 that they secured 30 million doses of NVX-CoV2373 through an agreement with the Serum Institute of India, the second vaccine deal signed by the national government, according to Agence France-Presse. The first was with AstraZeneca for 2.6 million doses of its vaccine, developed with Oxford University.
The Novavax vaccine will be available from the third quarter, at a price that has yet to be finalized. The government hopes to secure 148 million doses this year from seven companies—enough for around 70% of its population.
In announcing fourth quarter and full-year 2020 results on March 1, Novavax said it could file for an emergency use authorization with the FDA in the second quarter of 2021. Novavax hopes it can use data from its Phase III U.K. clinical trial in its FDA submission, and expects the FDA to examine data in May, a month after they are reviewed by regulators in the U.K., President and CEO Stanley C. Erck said on CNBC. Should the FDA insist on waiting for U.S. data, the agency may push the review timeline by one or two months, he added.
The company also said that NVX-CoV2373 showed 95.6% efficacy against the original strain of COVID-19 and 85.6% against the UK variant strain, and re-stated an earlier finding that its vaccine met the Phase III trial’s primary endpoint met with an efficacy rate of 89.3%.
Novavax said February 26 that it signed an exclusive license agreement with Takeda Pharmaceutical for Takeda to develop, manufacture, and commercialize NVX-CoV2373 in Japan.
Novavax agreed to transfer the technology for manufacturing of the vaccine antigen and will supply its Matrix-M™ adjuvant to Takeda. Takeda anticipated the capacity to manufacture over 250 million doses of the COVID-19 vaccine per year. Takeda agreed in return to pay Novavax undisclosed payments tied to achieving development and commercial milestones, plus a portion of proceeds from the vaccine.
Takeda also disclosed that it dosed the first participants in a Phase II clinical trial to test the immunogenicity and safety of Novavax’ vaccine candidate in Japanese participants.
Novavax on February 18 announced a memorandum of understanding with Gavi, the Vaccine Alliance (Gavi), to provide 1.1 billion cumulative doses of NVX-CoV2373 for the COVAX Facility. Gavi leads the design and implementation of the COVAX Facility, created to supply vaccines globally, and has committed to working with Novavax to finalize an advance purchase agreement for vaccine supply and global distribution allocation via the COVAX Facility and its partners.
The doses will be manufactured and distributed globally by Novavax and Serum Institute of India (SII), the latter under an existing agreement between Gavi and SII.
Novavax and SK Bioscience said February 15 that they expanded their collaboration and license agreement, with SK finalizing an agreement to supply 40 million doses of NVX-CoV2373 to the government of South Korea beginning in 2021, for an undisclosed price. SK also obtained a license to manufacture and commercialize NVX-CoV2373 for sale to South Korea, as a result of which SK said it will add significant production capacity.
The agreement also calls on Novavax to facilitate technology transfer related to the manufacturing of its protein antigen, its Matrix M adjuvant, and support to SK Bioscience as needed to secure regulatory approval.
Rolling review begins—On February 4, Novavax announced it had begun a rolling review process for authorization of NVX-CoV2373 with several regulatory agencies worldwide, including the FDA, the European Medicines Agency, the U.K. Medicines and Healthcare products Regulatory Agency (MHRA), and Health Canada. The reviews will continue while the company completes its pivotal Phase III trials in the U.S. and U.K., and through initial authorization for emergency use granted under country-specific regulations, and through initial authorization for emergency use.
A day earlier, Novavax executed a binding Heads of Terms agreement with the government of Switzerland to supply 6 million doses of NVX-CoV2373, to the country. Novavax and Switzerland plan to negotiate a final agreement, with initial delivery of vaccine doses slated to ship following successful clinical development and regulatory review.
On January 28, Novavax electrified investors by announcing that its COVID-19 vaccine NVX-CoV2373 showed efficacy of 89.3% in the company’s first analysis of data from a Phase III trial in the U.K., where a variant strain (B.1.1.7) accounted for about half of all positive cases.
However, NVX-CoV2373 achieved only 60% efficacy in a Phase IIb trial in South Africa, where that country’s escape variant of the virus (B.1.351, also known as 20H/501Y.V2) was seen in 90% of cases, Novavax said.
Novavax said January 7 it executed an Advance Purchase Agreement with the Commonwealth of Australia for 51 million doses of NVX-CoV2373 for an undisclosed price, with an option to purchase an additional 10 million doses—finalizing an agreement in principle announced in November 2020. Novavax said it will work with Australia’s Therapeutics Goods Administration (TGA), to obtain approvals upon showing efficacy in clinical studies. The company aims to deliver initial doses by mid-2021.
2020 Status: Phase III trial launched—Novavax said December 28 that it launched the pivotal Phase III PREVENT-19 trial (NCT04611802) in the U.S. and Mexico to evaluate the efficacy, safety and immunogenicity of NVX-CoV2373. The randomized, placebo-controlled, observer-blinded study will assess the efficacy, safety and immunogenicity of NVX-CoV2373 in up to 30,000 participants 18 years of age and older compared with placebo. The trial’s primary endpoint is the prevention of PCR-confirmed, symptomatic COVID-19. The key secondary endpoint is the prevention of PCR-confirmed, symptomatic moderate or severe COVID-19. Both endpoints will be assessed at least seven days after the second study vaccination in volunteers who have not been previously infected with SARS-CoV-2.
Two thirds of the participants will be assigned to randomly receive two intramuscular injections of the vaccine, administered 21 days apart, while one third of the trial participants will receive placebo. Trial sites were selected in locations where transmission rates are currently high, to accelerate the accumulation of positive cases that could show efficacy. Participants will be followed for 24 months following the second injection
PREVENT-19 is being conducted with support from federal agencies involved in Operation Warp Speed, the Trump administration’s effort to promote development and distribution of COVID-19 vaccines and drugs. Those agencies include the Department of Defense (DoD), the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), and the Biomedical Advanced Research and Development Authority (BARDA)—which has committed up to $1.6 billion to Novavax under a DoD agreement (identifier MCDC OTA agreement number W15QKN-16-9-1002).
Novavax is also conducting a pivotal Phase III study in the United Kingdom, a Phase IIb safety and efficacy study in South Africa, and an ongoing Phase I/II trial in the U.S. and Australia. Data from these trials are expected as soon as early first quarter 2021, though timing will depend on transmission rates in the regions, the company said.
Novavax said November 9 that the FDA granted its Fast Track designation for NVX-CoV2373. By the end of November, the company expected to finish enrollment in its Phase III U.K. trial, with interim data in that study expected as soon as early first quarter 2021.
Five days earlier, Novavax signed a non-binding Heads of Terms document with the Australian government to supply 40 million doses of NVX-CoV2373 to Australia starting as early as the first half of 2021, subject to the successful completion of Phase III clinical development and approval of the vaccine by Australia’s Therapeutic Goods Administration (TGA). The vaccine regimen is expected to require two doses per individual, administered 21 days apart.
Australia joins the U.S., the U.K., and Canada in signing direct supply agreements with Novavax. The company is supplying doses in Japan, South Korea, and India through partnerships. Australian clinical researchers led the global Phase I clinical trial in August, which involved 131 Australians across two trial sites (Melbourne and Brisbane). Also, approximately 690 Australians have participated in the Phase II arm of the clinical trial, which has been conducted across up to 40 sites in Australia and the U.S.
Novavax joined officials in its headquarters city of Gaithersburg, MD, on November 2 to announce expansion plans. The company plans to take 122,000 square feet of space at 700 Quince Orchard Road, and has committed to adding at least 400 local jobs, nearly doubling its current workforce of 450 worldwide. Most of the new jobs are expected to be added b March 2021.
Maryland’s Department of Commerce—which has prioritized assistance to life sciences companies—approved a $2 million conditional loan tied to job creation and capital investment. The state has also approved a $200,000 Partnership for Workforce Quality training grant, and the company is eligible for several tax credits, including the Job Creation Tax Credit and More Jobs for Marylanders.
Additionally, Montgomery County has approved a $500,000 grant tied to job creation and capital investment, while the City of Gaithersburg said it will approve a grant of up to $50,000 from its Economic Development Opportunity Fund. The city accelerated its planning approval process to accommodate Novavax’ timeline, given the company’s role in fighting COVID-19 and resulting assistance from Operation Warp Speed, the Trump administration’s effort to accelerate development of COVID-19 vaccines.
On October 27, Novavax said that it had enrolled 5,500 volunteers in the Phase III U.K. trial, which has been expanded from 10,000 to 15,000 volunteers. The increased enrollment “is likely to facilitate assessment of safety and efficacy in a shorter time period,” according to the company.
The trial, which is being conducted with the U.K. Government’s Vaccines Taskforce, was launched in September and is expected to be fully enrolled by the end of November, with interim data expected by early first quarter 2021, depending on the overall COVID-19 attack rate. Novavax has posted the protocol for the Phase III U.K. trial online. The protocol calls for unblinding of data once 152 participants have achieved mild, moderate or severe endpoints. Two interim analyses are planned upon occurrence of 66 and 110 endpoints.
Novavax also said it expects to launch a second Phase III trial designed to enroll up to 30,000 participants in the U.S. and Mexico by the end of November—a study funded through the U.S. government’s Operation Warp Speed program. The patient population will reflect proportional representation of diverse populations most vulnerable to COVID-19, across race/ethnicity, age, and co-morbidities.
The company cited progress toward large-scale manufacturing while acknowledging delays from original timeframe estimates. Novavax said it will use its contract manufacturing site at FUJIFILM Diosynth Biotechnologies’ Morrisville, NC facility to produce material for the U.S. trial.
On September 25, Novavax entered into a non-exclusive agreement with Endo International subsidiary Par Sterile Products to provide fill-finish manufacturing services at its plant in Rochester, MI, for NVX-CoV2373. Under the agreement, whose value was not disclosed, the Rochester facility has begun production of NVX-CoV2373 final drug product, with initial batches to be used in Novavax’ Phase III clinical trial in the U.S. Par Sterile will also fill-finish NVX-CoV2373 vaccine intended for commercial distribution in the U.S.
A day earlier, Novavax launched the U.K. trial. The randomized, placebo-controlled, observer-blinded study to evaluate the efficacy, safety and immunogenicity of NVX-CoV2373 with Matrix-M in up to 10,000 subjects 18-84 years of age, with and without “relevant” comorbidities, over the following four to six weeks, Novavax said. Half the participants will receive two intramuscular injections of vaccine comprising 5 µg of protein antigen with 50 µg Matrix‑M adjuvant, 21 days apart, while half of the trial participants will receive placebo. At least 25% of the study population will be over age 65.
The trial’s first primary endpoint is first occurrence of PCR-confirmed symptomatic COVID-19 with onset at least seven days after the second study vaccination in volunteers who have not been previously infected with SARS-CoV-2. The second primary endpoint is first occurrence of PCR-confirmed symptomatic moderate or severe COVID-19 with onset at least seven days after the second study vaccination in volunteers who have not been previously infected with SARS-CoV-2
“The data from this trial is expected to support regulatory submissions for licensure in the UK, EU and other countries,” stated Gregory M. Glenn, M.D., President, Research and Development at Novavax.
Maryland Gov. Larry Hogan joined state Secretary of Commerce Kelly M. Schulz and local officials in marking the launch of Phase III studies with a tour of the company’s facilities in Gaithersburg: “The coronavirus vaccine candidate that’s been developed by Novavax is one of the most promising in the country, if not the world.”
On August 31, Novavax reached an agreement in principle with the government of Canada to supply up to 76 million doses of NVX-CoV2373. The value was not disclosed. Novavax and Canada did say that they expect to finalize an advance purchase agreement under which Novavax will agree to supply doses of NVX-CoV2373 to Canada beginning as early as the second quarter of 2021.
The purchase arrangement will be subject to licensure of the NVX-CoV2373 by Health Canada, Novavax said. The vaccine is in multiple Phase II clinical trials: On August 24, Novavax said the first volunteers had been enrolled in the Phase II portion of its ongoing Phase I/II clinical trial (NCT04368988), designed to evaluate the immunogenicity and safety of two doses of of NVX-CoV2373 (5 and 25 µg) with and without 50 µg of Matrix‑M™ adjuvant in up to 1,500 volunteers ages 18-84.
The randomized, placebo-controlled, observer-blinded study is designed to assess two dose sizes (5 and 25 µg) of NVX-CoV2373, each with 50 µg of Matrix‑M. Unlike the Phase I portion, the Phase II portion will include older adults 60-84 years of age as approximately half of the trial’s population. Secondary objectives include preliminary evaluation of efficacy. The trial will be conducted at up to 40 sites in the U.S. and Australia, Novovax said.
NVX-CoV2373 is in a pair of Phase II trials launched in August—including a Phase IIb study in South Africa to assess efficacy, and a Phase II safety and immunogenicity study in the U.S. and Australia.
On August 14, the U.K. government agreed to purchase 60 million doses of NVX-CoV2373 from the company, and support its planned Phase III clinical trial in the U.K., through an agreement whose value was not disclosed. The doses are set to be manufactured as early as the first quarter of 2021.
The trial will be designed to evaluate the ability of NVX-CoV2373 to protect against symptomatic COVID-19 disease as well as evaluate antibody and T-cell responses. The randomized, double-blind, placebo-controlled efficacy study will enroll approximately 9,000 adults 18-85 years of age in the U.K., and is expected to start in the third quarter.
Novavax also said it will expand its collaboration with FUJIFILM Diosynth Biotechnologies (FDB), which will manufacture the antigen component of NVX-CoV2373 from its Billingham, Stockton-on-Tees site in the U.K., as well as at U.S. sites in Morrisville, NC, and College Station, TX. FDB’s U.K. sitevis expected to produce up to 180 million doses annually.
On August 13, Novavax said it signed a development and supply agreement for the antigen component of NVX-CoV2373 with Seoul-based SK bioscience, a vaccine business subsidiary of SK Group. The agreement calls for supply to global markets that include the COVAX Facility, co-led by Gavi, the Coalition for Epidemic Preparedness Innovations (CEPI) and the World Health Organization.
Novavax and SK signed a letter of intent with South Korea’s Ministry of Health and Welfare to work toward broad and equitable access to NVX-CoV2373 worldwide, as well as to make the vaccine available in South Korea. SK bioscience agreed to manufacture the vaccine antigen component for use in the final drug product globally during the pandemic, at its vaccine facility in Andong L-house, South Korea, beginning in August. The value of the agreement was not disclosed.
On August 7, Novavax licensed its COVID-19 vaccine technology to Takeda Pharmaceutical through a partnership by which Takeda will develop, manufacture, and commercialize NVX‑CoV2373 in Japan, using Matrix-M adjuvant to be supplied by Novavax. Takeda will also be responsible for regulatory submission to Japan’s Ministry of Health, Labour and Welfare (MHLW).
MHLW agreed to provide funding to Takeda—the amount was not disclosed in the companies’ announcement—for technology transfer, establishment of infrastructure, and scale-up of manufacturing. Takeda said it anticipated the capacity to manufacture over 250 million doses of NVX‑CoV2373 per year.
Five days earlier, Serum Institute of India agreed to license rights from Novavax to NVX‑CoV2373 for development and commercialization in India as well as low- and middle-income countries (LMIC), through an agreement whose value was not disclosed. Novavax retains rights to NVX-CoV2373 elsewhere in the world.
Novavax and Serum Institute of India agreed to partner on clinical development, co-formulation, filling and finishing and commercialization of NVX-CoV2373. Serum Institute will oversee regulatory submissions and marketing authorizations in regions covered by the collaboration. Novavax agreed to provide both vaccine antigen and Matrix‑M adjuvant, while the partners said they were in talks to have the Serum Institute manufacture vaccine antigen in India. Novavax and Seerum Institute plan to split the revenue from the sale of product, net of agreed costs.
A day earlier, Novavax announced positive results from the Phase I portion of its Phase I/II clinical trial (NCT04368988), designed to evaluate two doses of NVX-CoV2373 (5 and 25 µg) with and without Matrix‑M™ adjuvant in 131 healthy adults ages 18-59. NVX-CoV2373, adjuvanted with Matrix-M, elicited robust antibody responses numerically superior to human convalescent sera, according to data submitted for peer-review to a scientific journal.
All participants developed anti-spike IgG antibodies after a single dose of vaccine, Novavax said, many also developing wild-type virus neutralizing antibody responses. After the second dose, all participants developed wild-type virus neutralizing antibody responses. Both anti-spike IgG and viral neutralization responses compared favorably to responses from patients with clinically significant COVID‑19 disease, the company said—adding that IgG antibody response was highly correlated with neutralization titers, showing that a significant proportion of antibodies were functional.
For both dosages of NVX‑CoV2373 with adjuvant, the 5 µg dose performed “comparably” with the 25 µg dose, Novavax said. NVX‑CoV2373 also induced antigen-specific polyfunctional CD4+ T cell responses with a strong bias toward the Th1 phenotype (IFN-g, IL-2, and TNF-a).
Based on an interim analysis of Phase I safety and immunogenicity data, the trial was expanded to Phase II clinical trials in multiple countries, including the U.S. The trial—which began in Australia in May—is being funded by up-to $388 million in funding from the Coalition for Epidemic Preparedness Innovations (CEPI). If the Phase I/II trial is successful, CEPI said, it anticipates supporting further clinical development that would advance NVX-CoV2373 through to licensure.
On July 23, Novavax joined FDB to announce that FDB will manufacture bulk drug substance for NVX-CoV2373, under an agreement whose value was not disclosed. FDB’s site in Morrisville, NC has begun production of the first batch of NVX-CoV2373. Batches produced at FDB’s Morrisville site will be used in Novavax’s planned pivotal Phase III clinical trial, designed to assess NVX-CoV2373 in up to 30,000 participants, and set to start this fall.
The Phase III trial is among R&D efforts to be funded through the $1.6 billion awarded in July to Novavax through President Donald Trump’s “Operation Warp Speed” program toward late-stage clinical trials and large-scale manufacturing to produce 100 million doses of its COVID-19 vaccine by year’s end. Novavax said the funding will enable it to complete late-stage clinical studies aimed at evaluating the safety and efficacy of NVX-CoV2373.
In June, Novavax said biotech investor and executive David Mott was joining its board as an independent director, after recently acquiring nearly 65,000 shares of the company’s common stock. Also, Novavax was awarded a $60 million contract by the U.S. Department of Defense (DoD) for the manufacturing of NVX‑CoV2373. Through the Defense Health Program, the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense Enabling Biotechnologies (JPEO-CBRND-EB) agreed to support production of several vaccine components to be manufactured in the U.S. Novavax plans to deliver this year for DoD 10 million doses of NVX‑CoV2373 that could be used in Phase II/III trials, or under an Emergency Use Authorization (EUA) if approved by the FDA.
Also in June, AGC Biologics said it will partner with Novavax on large-scale GMP production of Matrix-M– significantly increasing Novavax’ capacity to deliver doses in 2020 and 2021—through an agreement whose value was not disclosed. And Novavax joined The PolyPeptide Group to announce large-scale GMP production by the global CDMO of two unspecified key intermediate components used in the production of Matrix-M.
In May, Novavax acquired Praha Vaccines from the India-based Cyrus Poonawalla Group for $167 million cash, in a deal designed to ramp up Novavax’s manufacturing capacity for NVX-CoV2373. Praha Vaccines’ assets include a 150,000-square foot vaccine and biologics manufacturing facility and other support buildings in Bohumil, Czech Republic. Novavax said the Bohumil facility is expected to deliver an annual capacity of over 1 billion doses of antigen starting in 2021 for the COVID-19 vaccine.
The Bohumil facility is completing renovations that include the addition of Biosafety Level-3 (BSL-3) capabilities. The site’s approximately 150 employees with “significant experience” in vaccine manufacturing and support have joined Novavax, the company said.
On May 11, Novavax joined CEPI in announcing up to $384 million in additional funding for the company toward clinical development and large-scale manufacturing of NVX-CoV2373. CEPI agreed to fund preclinical as well as Phase I and Phase II studies of NVX-CoV2373. The funding multiplied CEPI’s initial $4 million investment in the vaccine candidate, made two months earlier. Novavax’s total $388 million in CEPI funding accounted for 87% of the total $446 million awarded by the Coalition toward COVID-19 vaccine R&D as of that date.
Novavax identified its COVID-19 vaccine candidate in April. The company said NVX-CoV2373 was shown to be highly immunogenic in animal models measuring spike protein-specific antibodies, antibodies that block the binding of the spike protein to the receptor, and wild-type virus neutralizing antibodies. High levels of spike protein-specific antibodies with ACE-2 human receptor binding domain blocking activity and SARS-CoV-2 wild-type virus neutralizing antibodies were also seen after a single immunization.
In March, Emergent Biosolutions disclosed it retained an option to allocate manufacturing capacity for an expanded COVID-19 program under an agreement with Novavax to provide “molecule-to-market” contract development and manufacturing (CDMO) services to produce Novavax’s NanoFlu™, its recombinant quadrivalent seasonal influenza vaccine candidate.
Earlier in March, Emergent announced similar services to support clinical development of Novavax’s COVID-19 vaccine candidate, saying March 10 it agreed to produce the vaccine candidate and had initiated work, anticipating the vaccine candidate will be used in a Phase I study within the next four months. In February, Novavax said it had produced and was assessing multiple nanoparticle vaccine candidates in animal models prior to identifying an optimal candidate for human testing.
The Novavax COVID-19 vaccine, codenamed NVX-CoV2373, and also called SARS-CoV-2 rS (recombinant spike) protein nanoparticle with Matrix-M1 adjuvant, is a COVID-19 vaccine candidate developed by Novavax and Coalition for Epidemic Preparedness Innovations (CEPI). It requires two doses[1] and is stable at 2 to 8 °C (36 to 46 °F) (refrigerated).[2]
The vaccine is produced by creating an engineered baculovirus containing a gene for a modified SARS-CoV-2spike protein. The baculovirus then infects a culture of Sf9moth cells, which create the spike protein and display it on their cell membranes. The spike proteins are then harvested and assembled onto a synthetic lipid nanoparticle about 50 nanometers across, each displaying up to 14 spike proteins.[3][4][8]
In January 2020, Novavax announced development of a vaccine candidate, codenamed NVX-CoV2373, to establish immunity to SARS-CoV-2.[9] Novavax’s work is in competition for vaccine development among dozens of other companies.[10]
In March 2020, Novavax announced a collaboration with Emergent BioSolutions for preclinical and early-stage human research on the vaccine candidate.[11] Under the partnership, Emergent BioSolutions will manufacture the vaccine at large scale at their Baltimore facility.[12] Trials have also taken place in the United Kingdom, and subject to regulatory approval, at least 60 million doses will be manufactured by Fujifilm Diosynth Biotechnologies in Billingham for purchase by the UK government.[13][14] They also signed an agreement with Serum Institute of India for mass scale production for developing and low-income countries.[15] It has also been reported, that the vaccine will be manufactured in Spain.[16] The first human safety studies of the candidate, codenamed NVX-CoV2373, started in May 2020 in Australia.[17][18]
In July, the company announced it might receive $1.6 billion from Operation Warp Speed to expedite development of its coronavirus vaccine candidate by 2021—if clinical trials show the vaccine to be effective.[19][20] A spokesperson for Novavax stated that the $1.6 billion was coming from a “collaboration” between the Department of Health and Human Services and Department of Defense,[19][20] where Gen. Gustave F. Perna has been selected as COO for Warp Speed. In late September, Novavax entered the final stages of testing its coronavirus vaccine in the UK. Another large trial was announced to start by October in the US.[21]
In December 2020, Novavax started the PREVENT-19 (NCT04611802) Phase III trial in the US and Mexico.[22][full citation needed][23]
On 28 January 2021, Novavax reported that preliminary results from the United Kingdom trial showed that its vaccine candidate was more than 89% effective.[24][2] However, interim results from a trial in South Africa showed a lower effectiveness rate against the 501.V2 variant of the virus, at around 50-60%.[1][25]
On 12 March 2021, they announced their vaccine candidate was 96.4% effective in preventing the original strain of COVID-19 and 86% effective against the U.K variant. It proved 55% effective against the South African variant in people without HIV/AIDS. It was also 100% effective at preventing severe illness.[citation needed]
Deployment
On 2 February 2021, the Canadian Prime Minister Justin Trudeau announced that Canada has signed a tentative agreement for Novavax to produce millions of doses of its COVID-19 vaccine in Montreal, Canada, once it’s approved for use by Health Canada, making it the first COVID-19 vaccine to be produced domestically.[26]
^ Clinical trial number NCT04611802 for “A Study Looking at the Efficacy, Immune Response, and Safety of a COVID-19 Vaccine in Adults at Risk for SARS-CoV-2” at ClinicalTrials.gov
Launched – 1985, in Japan by Ono for the oral treatment of postoperative reflux esophagitis and chronic pancreatitis.
Camostat mesilate is a synthetic serine protease inhibitor that has been launched in Japan by Ono for the oral treatment of postoperative reflux esophagitis and chronic pancreatitis. It has been demonstrated that the drug has the ability to inhibit proteases such as trypsin, kallikrein, thrombin, plasmin, and C1 esterase, and that it decreases inflammation by directly suppressing the activity of monocytes and pancreatic stellate cells (PSCs).
In 2011, orphan drug designation was received in the U.S. by Stason Pharmaceuticals for the treatment of chronic pancreatitis. In 2017, Kangen Pharmaceuticals acquired KC Specialty Therapeutics (formerly a wholly-owned subsidiary of Stason Pharmaceuticals).
Camostat (INN; development code FOY-305) is a serine protease inhibitor. Serine protease enzymes have a variety of functions in the body, and so camostat has a diverse range of uses. It is used in the treatment of some forms of cancer and is also effective against some viral infections, as well as inhibiting fibrosis in liver or kidney disease or pancreatitis.[1][2][3][4][5] It is approved in Japan for the treatment of pancreatitis.[6][7]
An in vitro study shows that Camostat reduces significantly the infection of Calu-3 lung cells by SARS-CoV-2, the virus responsible for COVID-19.[8]
SYN
DE 2548886; FR 2289181; GB 1472700; JP 76054530; US 4021472
The reaction of p-hydrophenylacetic acid (I) with N,N-dimethylbromoacetamide (II) by means of triethylamine in reftuxing acetonitrile gives N,N-dimethylcarbamoylmethyl-p-hydroxyphenylacetate (III), which is then condensed with p-guanidinobenzoyl chloride (IV) [obtained from the corresponding acid p-guanidinobenzoic acid (V) and thionyl chloride] in pyridine.
By reaction of N,N-dimethylcarbamoylmethyl-p-(p-aminobenzoyloxy)phenylacetate (VI) with cyanamide (VII).
Camostat mesilate, chemical name is 4-(4-guanidine radicals benzoyloxy group) toluylic acid-N, N-dimethyl carbamoyl methyl esters mesylate, be the non-peptide proteinoid enzyme inhibitors of Japanese little Ye medicine Co., Ltd. exploitation, first in January, 1985 go on the market with trade(brand)name Foipan in Japan.Pharmacological evaluation shows: camostat mesilate has very strong restraining effect to trypsinase, kallikrein, Tryptase, zymoplasm, C1 esterase, oral rear kassinin kinin generation system, fibrinolytic system, blood coagulation system and the complement system acting on rapidly body, suppress the exception of the enzymic activity of these systems hyperfunction, thus control the symptom of chronic pancreatitis, alleviating pain, reduce amylase value, the clinical alleviation for chronic pancreatitis acute symptom.In addition, this product is also used for the treatment of diffusivity blood vessel blood coagulation disease.Pharmacological evaluation also finds, camostat mesilate also has the effects such as anticancer, antiviral, and effectively can reduce proteinuria, and play the effect of preliminary conditioning, further research is still underway.Current this product not yet in Discussion on Chinese Listed, also without the report succeeded in developing.
A preparation method for camostat mesilate, comprises the steps:
(1), by 160g methylene dichloride DCM join stirring in reaction vessel, cooling, be cooled to start when 0–10 DEG C to drip 51g 50% dimethylamine agueous solution, drip 30g chloroacetyl chloride simultaneously; Drip process control temp 5–10 DEG C, system pH controls 4-7, at 5–10 DEG C, react 1h after dripping off, reaction process pH controls 5-7, and reaction terminates rear standing 20min, separatory, water layer is with 54g dichloromethane extraction, and organic layer is concentrating under reduced pressure below 80 DEG C, obtains 3-pyrrolidone hydrochloride, crude, 3-pyrrolidone hydrochloride, crude carries out underpressure distillation within 130 DEG C, obtains 3-pyrrolidone hydrochloride distillation product; Output is 31g;
(2), the 3-pyrrolidone hydrochloride of 30.6g, 9g triethylamine TEA, 0.4g sodium bisulfite and 40g p-hydroxyphenylaceticacid p-hydroxyphenylaceticacid drop in order in reaction vessel and carry out stirring at low speed, and then drip the triethylamine of 17.6g, dropping temperature 40-95 DEG C, drip off rear maintenance 80-95 DEG C reaction 3h, after reaction terminates, add aqueous solution of sodium bisulfite (0.05gNaHSO3+90gH2O), add and start more than temperature 70 C, add finishing temperature more than 48 DEG C, after adding, cool, crystal seed is added when 40 DEG C, keep cooling temperature 0-5 DEG C, crystallization 2h, filter after crystallization, filter cake 100g purified water is washed, camostat mesilate crude product is obtained after draining, camostat mesilate crude product, 50mL ethyl acetate are joined heating for dissolving in aqueous solution of sodium bisulfite (0.2g NaHSO3+20g H2O), after having dissolved, cooling crystallization, keep recrystallization temperature 0-5 DEG C, crystallization time 1h, suction filtration after crystallization, filter cake, with 10mL water washing, washs with 20mL ethyl acetate after draining again, again at 60 ± 3 DEG C of drying under reduced pressure 2h after draining, obtain camostat mesilate refined silk, output is about 47g,
(3), the camostat mesilate refined silk of 47g is joined heating for dissolving in 30mL acetonitrile, after dissolving terminates, cooling temperature is to 0-5 DEG C, crystallization 1h, after crystallization terminates, suction filtration, filter cake with 17mL acetonitrile wash, drain, drying under reduced pressure 2h at 60 ± 3 DEG C, obtain camostat mesilate product, output is about 45g.
German researchers identify potential drug for Covid-19
Scientists at the German Primate Center – Leibniz Institute for Primate Research have found that an existing drug may help treat Covid-19.
As well as Charité – Universitätsmedizin Berlin, the scientists worked with researchers at the University of Veterinary Medicine Hannover Foundation, the BG-Unfallklinik Murnau, the LMU Munich, the Robert Koch Institute and the German Center for Infection Research.
The research aimed to understand the entry of the novel coronavirus, SARS-CoV-2, into host cells, as well as determine approaches to block the process.
Research findings showed that SARS-CoV-2 requires cellular protein TMPRSS2 to enter hosts’ lung cells.
German Primate Center Infection Biology Unit head Stefan Pöhlmann said: “Our results show that SARS-CoV-2 requires the protease TMPRSS2, which is present in the human body, to enter cells. This protease is a potential target for therapeutic intervention.”
Summary: A clinically proven drug known to block an enzyme essential for the viral entry of Coronavirus into the lungs blocks the COVID 19 (SARS-CoV-2) infection. The drug, Camostat mesilate, is a drug approved in Japan to treat pancreatic inflammation. Results suggest this drug may also protect against COVID 19. Researchers call for further clinical trials.
Viruses must enter cells of the human body to cause disease. For this, they attach to suitable cells and inject their genetic information into these cells. Infection biologists from the German Primate Center – Leibniz Institute for Primate Research in Göttingen, together with colleagues at Charité – Universitätsmedizin Berlin, have investigated how the novel coronavirus SARS-CoV-2 penetrates cells. They have identified a cellular enzyme that is essential for viral entry into lung cells: the protease TMPRSS2. A clinically proven drug known to be active against TMPRSS2 was found to block SARS-CoV-2 infection and might constitute a novel treatment option.
The findings have been published in Cell.
Several coronaviruses circulate worldwide and constantly infect humans, which normally caused only mild respiratory disease. Currently, however, we are witnessing a worldwide spread of a new coronavirus with more than 101,000 confirmed cases and almost 3,500 deaths. The new virus has been named SARS coronavirus-2 and has been transmitted from animals to humans. It causes a respiratory disease called COVID-19 that may take a severe course. The SARS coronavirus-2 has been spreading since December 2019 and is closely related to the SARS coronavirus that caused the SARS pandemic in 2002/2003. No vaccines or drugs are currently available to combat these viruses.
Stopping virus spread
A team of scientists led by infection biologists from the German Primate Centre and including researchers from Charité, the University of Veterinary Medicine Hannover Foundation, the BG-Unfallklinik Murnau, the LMU Munich, the Robert Koch Institute and the German Center for Infection Research, wanted to find out how the new coronavirus SARS-CoV-2 enters host cells and how this process can be blocked. The researchers identified a cellular protein that is important for the entry of SARS-CoV-2 into lung cells. “Our results show that SARS-CoV-2 requires the protease TMPRSS2, which is present in the human body, to enter cells,” says Stefan Pöhlmann, head of the Infection Biology Unit at the German Primate Center. “This protease is a potential target for therapeutic intervention.”
The SARS coronavirus-2 has been spreading since December 2019 and is closely related to the SARS coronavirus that caused the SARS pandemic in 2002/2003. No vaccines or drugs are currently available to combat these viruses. The image is credited to CDC.
Promising drug
Since it is known that the drug camostat mesilate inhibits the protease TMPRSS2, the researchers have investigated whether it can also prevent infection with SARS-CoV-2. “We have tested SARS-CoV-2 isolated from a patient and found that camostat mesilate blocks entry of the virus into lung cells,” says Markus Hoffmann, the lead author of the study. Camostat mesilate is a drug approved in Japan for use in pancreatic inflammation. “Our results suggest that camostat mesilate might also protect against COVID-19,” says Markus Hoffmann. “This should be investigated in clinical trials.”
References
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^Hsieh, H. P.; Hsu, J. T. (2007). “Strategies of development of antiviral agents directed against influenza virus replication”. Current Pharmaceutical Design. 13 (34): 3531–42. doi:10.2174/138161207782794248. PMID18220789.
^Kitamura, K.; Tomita, K. (2012). “Proteolytic activation of the epithelial sodium channel and therapeutic application of a serine protease inhibitor for the treatment of salt-sensitive hypertension”. Clinical and Experimental Nephrology. 16 (1): 44–8. doi:10.1007/s10157-011-0506-1. PMID22038264.
Kunze H, Bohn E (May 1983). “Effects of the serine protease inhibitors FOY and FOY 305 on phospholipase A1 (EC 3.1.1.32) activity in rat – liver lysosomes”. Pharmacol Res Commun. 15 (5): 451–9. doi:10.1016/S0031-6989(83)80065-4. PMID6412250.
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