New Drug Approvals

Home » Posts tagged 'Breakthrough Therapy designations.'

Tag Archives: Breakthrough Therapy designations.

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

Blog Stats

  • 2,672,469 hits

Flag and hits

Flag Counter

Enter your email address to follow this blog and receive notifications of new posts by email.

Join 2,434 other followers

Follow New Drug Approvals on WordPress.com

Archives

Categories

Flag Counter

ORGANIC SPECTROSCOPY

Read all about Organic Spectroscopy on ORGANIC SPECTROSCOPY INTERNATIONAL 

Enter your email address to follow this blog and receive notifications of new posts by email.

Join 2,434 other followers

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

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 GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 30 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, Dr T.V. Radhakrishnan and Dr B. K. Kulkarni, 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, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 30 year tenure till date Dec 2017, 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 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 50 Lakh plus views on dozen plus blogs, 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 19 lakh plus views on New Drug Approvals Blog in 216 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

Personal Links

Verified Services

View Full Profile →

Archives

Categories

Flag Counter

FDA approves new HIV treatment Trogarzo (ibalizumab-uiyk) for patients who have limited treatment options


Image result for ibalizumab-uiykImage result for taiMed Biologics USA Corp

FDA approves new HIV treatment Trogarzo (ibalizumab-uiyk),for patients who have limited treatment options

Today, the U.S. Food and Drug Administration approved Trogarzo (ibalizumab-uiyk), a new type of antiretroviral medication for adult patients living with HIV who have tried multiple HIV medications in the past (heavily treatment-experienced) and whose HIV infections cannot be successfully treated with other currently available therapies (multidrug resistant HIV, or MDR HIV).Trogarzo is administered intravenously once every 14 days by a trained medical professional and used in combination with other antiretroviral medications. Continue reading.

 

 

March 6, 2018

Release

Today, the U.S. Food and Drug Administration approved Trogarzo (ibalizumab-uiyk), a new type of antiretroviral medication for adult patients living with HIV who have tried multiple HIV medications in the past (heavily treatment-experienced) and whose HIV infections cannot be successfully treated with other currently available therapies (multidrug resistant HIV, or MDR HIV).Trogarzo is administered intravenously once every 14 days by a trained medical professional and used in combination with other antiretroviral medications.

“While most patients living with HIV can be successfully treated using a combination of two or more antiretroviral drugs, a small percentage of patients who have taken many HIV drugs in the past have multidrug resistant HIV, limiting their treatment options and putting them at a high risk of HIV-related complications and progression to death,” said Jeff Murray, M.D., deputy director of the Division of Antiviral Products in the FDA’s Center for Drug Evaluation and Research. “Trogarzo is the first drug in a new class of antiretroviral medications that can provide significant benefit to patients who have run out of HIV treatment options. New treatment options may be able to improve their outcomes.”

The safety and efficacy of Trogarzo were evaluated in a clinical trial of 40 heavily treatment-experienced patients with MDR HIV-1 who continued to have high levels of virus (HIV-RNA) in their blood despite being on antiretroviral drugs. Many of the participants had previously been treated with 10 or more antiretroviral drugs. The majority of participants experienced a significant decrease in their HIV-RNA levels one week after Trogarzo was added to their failing antiretroviral regimens. After 24 weeks of Trogarzo plus other antiretroviral drugs, 43 percent of the trial’s participants achieved HIV RNA suppression.

The clinical trial focused on the small patient population with limited treatment options and demonstrated the benefit of Trogarzo in achieving reduction of HIV RNA. The seriousness of the disease, the need to individualize other drugs in the treatment regimen, and safety data from other trials were considered in evaluating the Trogarzo development program.

A total of 292 patients with HIV-1 infection have been exposed to Trogarzo IV infusion. The most common adverse reactions to Trogarzo were diarrhea, dizziness, nausea and rash. Severe side effects included rash and changes in the immune system (immune reconstitution syndrome).
The FDA granted this application Fast TrackPriority Review and Breakthrough Therapy designations. Trogarzo also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA granted approval of Trogarzo to TaiMed Biologics USA Corp.

Theratechnologies Announces FDA Approval of Breakthrough Therapy, Trogarzo™ (ibalizumab-uiyk) Injection, the First HIV-1 Inhibitor and Long-Acting Monoclonal Antibody for Multidrug Resistant HIV-1


NEWS PROVIDED BY

Theratechnologies Inc. 


  •  First HIV treatment approved with a new mechanism of action in more than 10 years
  • Infused every two weeks, only antiretroviral treatment (ART) that does not require daily dosing
  • Trogarzo™ has no drug-drug interactions and no cross-resistance with other ARTs

MONTREALMarch 6, 2018 /PRNewswire/ – Theratechnologies Inc. (Theratechnologies) (TSX: TH) and its partner TaiMed Biologics, Inc. (TaiMed) today announced that the U.S. Food and Drug Administration (FDA) has granted approval of Trogarzo™ (ibalizumab-uiyk) Injection. In combination with other ARTs, Trogarzo™ is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen.1

Trogarzo™ represents a critical new treatment advance as the first HIV therapy with a new mechanism of action approved in 10 years and proven effectiveness in difficult-to-treat patients with limited options. Unlike all other classes of ARTs, Trogarzo™ is a CD4-directed post-attachment HIV-1 inhibitor that binds to CD4+ receptors on host cells and blocks the HIV virus from infecting the cells.1

“Today’s approval of Trogarzo™ by the FDA is great news for people infected with difficult-to-treat multidrug resistant HIV. We look forward to bringing this much-needed therapy to patients in the U.S within six weeks,” said Luc Tanguay, President and Chief Executive Officer, Theratechnologies Inc. “We are grateful to the patients, investigators, as well as the FDA who supported the clinical development of Trogarzo™, and are helping address this critical unmet medical need.”

Trogarzo™ previously received Breakthrough Therapy and Orphan Drug designations as well as Priority Review status from the FDA, underscoring the significance of the treatment for this patient population.

“I witnessed some of the earliest cases of HIV and AIDS, at a time when the diagnosis was terrifying to patients because in many cases it was a death sentence,” said David Ho, M.D., chief scientific advisor of TaiMed and scientific director and CEO of the Aaron Diamond AIDS Research Center. “Since then, treatment advances and the discovery that combinations of ARTs was the best way to bring viral load below the level of detection have allowed most people to manage HIV like a chronic condition and live long, healthy lives. However, this is not the reality for people whose HIV is resistant to multiple drugs and whose viral load is not controlled, which is why TaiMed dedicated the past decade to advancing ibalizumab in the clinic. For these patients, it represents the next breakthrough.”

Up to 25,000 Americans with HIV are currently multidrug resistant, of which 12,000 are in urgent need of a new treatment option because their current treatment regimen is failing them and their viral load has risen to detectable levels, jeopardizing their health and making HIV transmittable.2-13 The best way to prevent the transmission of multidrug resistant HIV is to control the virus in those living with it. According to new guidance from the Centers for Disease Control and Prevention (CDC), the HIV virus cannot be transmitted if it is being fully suppressed.13

“I’ve struggled with multidrug resistant HIV for almost 30 years and it was completely debilitating to feel like I had run out of options – I made no long-term plans,” said Nelson Vergel, founder of the Program for Wellness Restoration (PoWeR) and Trogarzo™ patient. “Since starting treatment with Trogarzo™ six years ago and getting my viral load to an undetectable level, I have been my happiest, most productive self. Trogarzo™ is a new source of hope and peace of mind for people whose treatments have failed them, and I feel incredibly lucky to have been able to participate in the clinical trial program.”

TaiMed and Theratechnologies partnered on the development of Trogarzo™ so patients who can benefit from the treatment have access to it. For patients who need assistance accessing Trogarzo™ or who face challenges affording medicines, Theratechnologies has a team of patient care coordinators available to help. Patients can get assistance and expert support by contacting THERA patient support™ at 1-833-23-THERA (84372).

“In Phase 3 ibalizumab trials, we saw marked improvements in patients’ health who not only were heavily treatment-experienced and had limited remaining treatment options, but in cases they also had extremely high viral loads and significantly impaired immune systems,” said Edwin DeJesus, M.D., Medical Director for the Orlando Immunology Center. “As an investigator for ibalizumab clinical trials over nearly 10 years, it was remarkable and inspiring to see the dramatic effect ibalizumab had on such vulnerable patients. As a clinician, I am excited that we will now have another option with a different mechanism of action for our heavily pretreated patients who are struggling to keep their viral load below detection because their HIV is resistant to multiple drugs.”

Clinical Trial Findings

Clinical studies show that Trogarzo™, in combination with other ARTs, significantly reduces viral load and increases CD4+ (T-cell) count among patients with multidrug resistant HIV-1.

The Phase 3 trial showed:1

  • Trogarzo™ significantly reduced viral load within seven days after the first dose of functional monotherapy and maintained the treatment response when combined with an optimized background regimen that included at least one other active ART for up to 24 weeks of treatment, while being safe and well tolerated.
  • More than 80% of patients achieved the study’s primary endpoint – at least a 0.5 log10 (or 70%) viral load reduction from baseline seven days after receiving a 2,000 mg loading dose of Trogarzo™ and no adjustment to the failing background regimen.
  • The average viral load reduction after 24 weeks was 1.6 log10 with 43% of patients achieving undetectable viral loads.

Patients experienced a clinically-significant mean increase in CD4+ T-cells of 44 cells/mm3, and increases varied based on T-cell count at baseline. Rebuilding the immune system by increasing T-cell count is particularly important as people with multidrug resistant HIV-1 often have the most advanced form of HIV.1

The most common drug-related adverse reactions (incidence ≥ 5%) were diarrhea (8%), dizziness (8%), nausea (5%) and rash (5%). No drug-drug interactions were reported with other ARTs or medications, and no cross-resistance with other ARTs were observed.1

About Trogarzo™ (ibalizumab-uiyk) Injection

Trogarzo™ is a humanized monoclonal antibody for the treatment of multidrug resistant HIV-1 infection. Trogarzo™ binds primarily to the second extracellular domain of the CD4+ T receptor, away from major histocompatibility complex II molecule binding sites. It prevents HIV from infecting CD4+ immune cells while preserving normal immunological function.

IMPORTANT SAFETY INFORMATION

Trogarzo™ is a prescription HIV medicine that is used with other antiretroviral medicines to treat human immunodeficiency virus-1 (HIV-1) infections in adults.

Trogarzo™ blocks HIV from infecting certain cells of the immune system. This prevents HIV from multiplying and can reduce the amount of HIV in the body.

Before you receive Trogarzo™, tell your healthcare provider if you:

  • are pregnant or plan to become pregnant. It is not known if Trogarzo™ may harm your unborn baby.
  • are breastfeeding or plan to breastfeed. It is not known if Trogarzo™ passes into breast milk.

Tell your healthcare provider about all the medicines you take, including all prescription and over-the-counter medicines, vitamins, and herbal supplements.

Trogarzo™ can cause serious side effects, including:

Changes in your immune system (Immune Reconstitution Inflammatory Syndrome) can happen when you start taking HIV-1 medicines.  Your immune system might get stronger and begin to fight infections that have been hidden in your body for a long time.  Tell your health care provider right away if you start having new symptoms after starting your HIV-1 medicine.

The most common side effects of Trogarzo™ include:

  • Diarrhea
  • Dizziness
  • Nausea
  • Rash

Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of Trogarzo™. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.  You may also report side effects to at 1-833-23THERA (1-833-238-4372).

 

About Theratechnologies

Theratechnologies (TSX: TH) is a specialty pharmaceutical company addressing unmet medical needs to promote healthy living and an improved quality of life among HIV patients. Further information about Theratechnologies is available on the Company’s website at www.theratech.com and on SEDAR at www.sedar.com.

/////Trogarzo, ibalizumab-uiyk, fda 2018, Fast TrackPriority Review, Breakthrough Therapy designations,  Orphan Drug designation

FDA approves new treatment for certain advanced or metastatic breast cancers


FDA approves new treatment for certain advanced or metastatic breast cancers

The U.S. Food and Drug Administration today approved Verzenio (abemaciclib) to treat adult patients who have hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer that has progressed after taking therapy that alters a patient’s hormones (endocrine therapy). Verzenio is approved to be given in combination with an endocrine therapy, called fulvestrant, after the cancer had grown on endocrine therapy. It is also approved to be given on its own, if patients were previously treated with endocrine therapy and chemotherapy after the cancer had spread (metastasized). Continue reading

https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm578071.htm

Abemaciclib.svg

(abemaciclib)

September 28, 2017

Release

The U.S. Food and Drug Administration today approved Verzenio (abemaciclib) to treat adult patients who have hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer that has progressed after taking therapy that alters a patient’s hormones (endocrine therapy). Verzenio is approved to be given in combination with an endocrine therapy, called fulvestrant, after the cancer had grown on endocrine therapy. It is also approved to be given on its own, if patients were previously treated with endocrine therapy and chemotherapy after the cancer had spread (metastasized).

“Verzenio provides a new targeted treatment option for certain patients with breast cancer who are not responding to treatment, and unlike other drugs in the class, it can be given as a stand-alone treatment to patients who were previously treated with endocrine therapy and chemotherapy,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

Verzenio works by blocking certain molecules (known as cyclin-dependent kinases 4 and 6), involved in promoting the growth of cancer cells. There are two other drugs in this class that are approved for certain patients with breast cancer, palbociclib approved in February 2015 and ribociclib approved in March 2017.

Breast cancer is the most common form of cancer in the United States. The National Cancer Institute at the National Institutes of Health estimates approximately 252,710 women will be diagnosed with breast cancer this year, and 40,610 will die of the disease. Approximately 72 percent of patients with breast cancer have tumors that are HR-positive and HER2-negative.

The safety and efficacy of Verzenio in combination with fulvestrant were studied in a randomized trial of 669 patients with HR-positive, HER2-negative breast cancer that had progressed after treatment with endocrine therapy and who had not received chemotherapy once the cancer had metastasized. The study measured the length of time tumors did not grow after treatment (progression-free survival). The median progression-free survival for patients taking Verzenio with fulvestrant was 16.4 months compared to 9.3 months for patients taking a placebo with fulvestrant.

The safety and efficacy of Verzenio as a stand-alone treatment were studied in a single-arm trial of 132 patients with HR-positive, HER2-negative breast cancer that had progressed after treatment with endocrine therapy and chemotherapy after the cancer metastasized. The study measured the percent of patients whose tumors completely or partially shrank after treatment (objective response rate). In the study, 19.7 percent of patients taking Verzenio experienced complete or partial shrinkage of their tumors for a median 8.6 months.

Common side effects of Verzenio include diarrhea, low levels of certain white blood cells (neutropenia and leukopenia), nausea, abdominal pain, infections, fatigue, low levels of red blood cells (anemia), decreased appetite, vomiting and headache.

Serious side effects of Verzenio include diarrhea, neutropenia, elevated liver blood tests and blood clots (deep venous thrombosis/pulmonary embolism). Women who are pregnant should not take Verzenio because it may cause harm to a developing fetus.

The FDA granted this application Priority Review and Breakthrough Therapydesignations.

The FDA granted the approval of Verzenio to Eli Lilly and Company.

//////////Verzenio, abemaciclib, fda 2017, metastatic breast cancers, Eli Lilly ,  Priority Review,  Breakthrough Therapy designations, antibodies

FDA approves Mavyret (glecaprevir and pibrentasvir) for Hepatitis C


Glecaprevir.svg
Glecaprevir
Pibrentasvir.svg
Pibrentasvir
08/03/2017 03:06 PM EDT
The U.S. Food and Drug Administration today approved Mavyret (glecaprevir and pibrentasvir) to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis (liver disease) or with mild cirrhosis, including patients with moderate to severe kidney disease and those who are on dialysis. Mavyret is also approved for adult patients with HCV genotype 1 infection who have been previously treated with a regimen either containing an NS5A inhibitor or an NS3/4A protease inhibitor but not both.

The U.S. Food and Drug Administration today approved Mavyret (glecaprevir and pibrentasvir) to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis (liver disease) or with mild cirrhosis, including patients with moderate to severe kidney disease and those who are on dialysis. Mavyret is also approved for adult patients with HCV genotype 1 infection who have been previously treated with a regimen either containing an NS5A inhibitor or an NS3/4A protease inhibitor but not both.

Mavyret is the first treatment of eight weeks duration approved for all HCV genotypes 1-6 in adult patients without cirrhosis who have not been previously treated. Standard treatment length was previously 12 weeks or more.

“This approval provides a shorter treatment duration for many patients, and also a treatment option for certain patients with genotype 1 infection, the most common HCV genotype in the United States, who were not successfully treated with other direct-acting antiviral treatments in the past,” said Edward Cox, M.D., director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research.

Hepatitis C is a viral disease that causes inflammation of the liver that can lead to diminished liver function or liver failure. According to the Centers for Disease Control and Prevention, an estimated 2.7 to 3.9 million people in the United States have chronic HCV. Some patients who suffer from chronic HCV infection over many years may have jaundice (yellowish eyes or skin) and complications, such as bleeding, fluid accumulation in the abdomen, infections, liver cancer and death.

There are at least six distinct HCV genotypes, or strains, which are genetically distinct groups of the virus. Knowing the strain of the virus can help inform treatment recommendations. Approximately 75 percent of Americans with HCV have genotype 1; 20-25 percent have genotypes 2 or 3; and a small number of patients are infected with genotypes 4, 5 or 6.

The safety and efficacy of Mavyret were evaluated during clinical trials enrolling approximately 2,300 adults with genotype 1, 2, 3, 4, 5 or 6 HCV infection without cirrhosis or with mild cirrhosis. Results of the trials demonstrated that 92-100 percent of patients who received Mavyret for eight, 12 or 16 weeks duration had no virus detected in the blood 12 weeks after finishing treatment, suggesting that patients’ infection had been cured.

Treatment duration with Mavyret differs depending on treatment history, viral genotype, and cirrhosis status.

The most common adverse reactions in patients taking Mavyret were headache, fatigue and nausea.

Mavyret is not recommended in patients with moderate cirrhosis and contraindicated in patients with severe cirrhosis. It is also contraindicated in patients taking the drugs atazanavir and rifampin.

Hepatitis B virus (HBV) reactivation has been reported in HCV/HBV coinfected adult patients who were undergoing or had completed treatment with HCV direct-acting antivirals, and who were not receiving HBV antiviral therapy. HBV reactivation in patients treated with direct-acting antiviral medicines can result in serious liver problems or death in some patients. Health care professionals should screen all patients for evidence of current or prior HBV infection before starting treatment with Mavyret.

The FDA granted this application Priority Review and Breakthrough Therapydesignations.

The FDA granted approval of Mavyret to AbbVie Inc.

////////// glecaprevir, pibrentasvir, fda 2017, Hepatitis C,  AbbVie Inc,  Priority Review, Breakthrough Therapy designations,
Glecaprevir
Glecaprevir.svg
Clinical data
Trade names Maviret (combination with pibrentasvir)
Routes of
administration
By mouth
ATC code
  • None
Legal status
Legal status
  • Investigational
Identifiers
Synonyms ABT-493
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
Chemical and physical data
Formula C38H46F4N6O9S
Molar mass 838.87 g·mol−1

Glecaprevir (INN,[1] codenamed ABT-493) is a hepatitis C virus (HCV) nonstructural (NS) protein 3/4A protease inhibitor that was identified jointly by AbbVie and Enanta Pharmaceuticals. It is being developed as a treatment of chronic hepatitis C infection in co-formulation with an HCV NS5A inhibitor pibrentasvir. Together they demonstrated potent antiviral activity against major HCV genotypes and high barriers to resistance in vitro.[2]

On December 19, 2016, AbbVie submitted New Drug Application to U.S. Food and Drug Administration for glecaprevir/pibrentasvir (trade name Maviret) regimen for the treatment of all major genotypes (1–6) of chronic hepatitis C.[3]

References

  1. Jump up^ “International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 76” (PDF). World Health Organization. p. 503. Retrieved 25 February 2017.
  2. Jump up^ Lawitz, EJ; O’Riordan, WD; Asatryan, A; Freilich, BL; Box, TD; Overcash, JS; Lovell, S; Ng, TI; Liu, W; Campbell, A; Lin, CW; Yao, B; Kort, J (28 December 2015). “Potent Antiviral Activities of the Direct-Acting Antivirals ABT-493 and ABT-530 with Three-Day Monotherapy for Hepatitis C Virus Genotype 1 Infection”Antimicrobial Agents and Chemotherapy60 (3): 1546–55. PMC 4775945Freely accessiblePMID 26711747doi:10.1128/AAC.02264-15.
  3. Jump up^ “AbbVie Submits New Drug Application to U.S. FDA for its Investigational Regimen of Glecaprevir/Pibrentasvir (G/P) for the Treatment of All Major Genotypes of Chronic Hepatitis C”. AbbVie Inc. North Chicago, Illinois, U.S.A. December 19, 2016. Retrieved 25 February 2017.
Pibrentasvir
INN: Pibrentasvir
Pibrentasvir.svg
Identifiers
Synonyms ABT-530
CAS Number
Chemical and physical data
Formula C57H65F5N10O8
Molar mass 1,113.20 g·mol−1

Pibrentasvir is an antiviral agent.[1] In the United States, it is approved for use with glecaprevir as the combination drug glecaprevir/pibrentasvir (Mavyret) for the treatment of hepatitis C.[2]

References

  1. Jump up^ Ng, Teresa I.; Krishnan, Preethi; Pilot-Matias, Tami; Kati, Warren; Schnell, Gretja; Beyer, Jill; Reisch, Thomas; Lu, Liangjun; Dekhtyar, Tatyana; Irvin, Michelle; Tripathi, Rakesh; Maring, Clarence; Randolph, John T.; Wagner, Rolf; Collins, Christine (2017). “In Vitro Antiviral Activity and Resistance Profile of the Next-Generation Hepatitis C Virus NS5A Inhibitor Pibrentasvir”. Antimicrobial Agents and Chemotherapy61 (5): e02558–16. PMID 28193664doi:10.1128/AAC.02558-16.
  2. Jump up^ Linda A. Johnson (August 3, 2017). “FDA OKs new drug to treat all forms of hepatitis C”. Fox Business.

FDA approves Vosevi for Hepatitis C


07/18/2017
The U.S. Food and Drug Administration today approved Vosevi to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis (liver disease) or with mild cirrhosis.

The U.S. Food and Drug Administration today approved Vosevi to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis (liver disease) or with mild cirrhosis. Vosevi is a fixed-dose, combination tablet containing two previously approved drugs – sofosbuvir and velpatasvir – and a new drug, voxilaprevir. Vosevi is the first treatment approved for patients who have been previously treated with the direct-acting antiviral drug sofosbuvir or other drugs for HCV that inhibit a protein called NS5A.

“Direct-acting antiviral drugs prevent the virus from multiplying and often cure HCV. Vosevi provides a treatment option for some patients who were not successfully treated with other HCV drugs in the past,” said Edward Cox, M.D., director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research.

Hepatitis C is a viral disease that causes inflammation of the liver that can lead to diminished liver function or liver failure. According to the Centers for Disease Control and Prevention, an estimated 2.7 to 3.9 million people in the United States have chronic HCV. Some patients who suffer from chronic HCV infection over many years may have jaundice (yellowish eyes or skin) and develop complications, such as bleeding, fluid accumulation in the abdomen, infections, liver cancer and death.

There are at least six distinct HCV genotypes, or strains, which are genetically distinct groups of the virus. Knowing the strain of the virus can help inform treatment recommendations. Approximately 75 percent of Americans with HCV have genotype 1; 20-25 percent have genotypes 2 or 3; and a small number of patients are infected with genotypes 4, 5 or 6.

The safety and efficacy of Vosevi was evaluated in two Phase 3 clinical trials that enrolled approximately 750 adults without cirrhosis or with mild cirrhosis.

The first trial compared 12 weeks of Vosevi treatment with placebo in adults with genotype 1 who had previously failed treatment with an NS5A inhibitor drug. Patients with genotypes 2, 3, 4, 5 or 6 all received Vosevi.

The second trial compared 12 weeks of Vosevi with the previously approved drugs sofosbuvir and velpatasvir in adults with genotypes 1, 2 or 3 who had previously failed treatment with sofosbuvir but not an NS5A inhibitor drug.

Results of both trials demonstrated that 96-97 percent of patients who received Vosevi had no virus detected in the blood 12 weeks after finishing treatment, suggesting that patients’ infection had been cured.

Treatment recommendations for Vosevi are different depending on viral genotype and prior treatment history.

The most common adverse reactions in patients taking Vosevi were headache, fatigue, diarrhea and nausea.

Vosevi is contraindicated in patients taking the drug rifampin.

Hepatitis B virus (HBV) reactivation has been reported in HCV/HBV coinfected adult patients who were undergoing or had completed treatment with HCV direct-acting antivirals, and who were not receiving HBV antiviral therapy. HBV reactivation in patients treated with direct-acting antiviral medicines can result in serious liver problems or death in some patients. Health care professionals should screen all patients for evidence of current or prior HBV infection before starting treatment with Vosevi.

The FDA granted this application Priority Review and Breakthrough Therapydesignations.

The FDA granted approval of Vosevi to Gilead Sciences Inc

//////////////Vosevi, Gilead Sciences Inc, Priority Review, Breakthrough Therapy designations, fda 2017, sofosbuvir,  velpatasvir , voxilaprevir, Hepatitis B

FDA approves first treatment for a form of Batten disease, Brineura (cerliponase alfa)


Image result
04/27/2017
The U.S. Food and Drug Administration today approved Brineura (cerliponase alfa) as a treatment for a specific form of Batten disease. Brineura is the first FDA-approved treatment to slow loss of walking ability (ambulation) in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase-1 (TPP1) deficiency.

The U.S. Food and Drug Administration today approved Brineura (cerliponase alfa) as a treatment for a specific form of Batten disease. Brineura is the first FDA-approved treatment to slow loss of walking ability (ambulation) in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase-1 (TPP1) deficiency.

“The FDA is committed to approving new and innovative therapies for patients with rare diseases, particularly where there are no approved treatment options,” said Julie Beitz, M.D., director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research. “Approving the first drug for the treatment of this form of Batten disease is an important advance for patients suffering with this condition.”

CLN2 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), collectively referred to as Batten disease. CLN2 disease is a rare inherited disorder that primarily affects the nervous system. In the late infantile form of the disease, signs and symptoms typically begin between ages 2 and 4. The initial symptoms usually include language delay, recurrent seizures (epilepsy) and difficulty coordinating movements (ataxia). Affected children also develop muscle twitches (myoclonus) and vision loss. CLN2 disease affects essential motor skills, such as sitting and walking. Individuals with this condition often require the use of a wheelchair by late childhood and typically do not survive past their teens. Batten disease is relatively rare, occurring in an estimated two to four of every 100,000 live births in the United States.

Brineura is an enzyme replacement therapy. Its active ingredient (cerliponase alfa) is a recombinant form of human TPP1, the enzyme deficient in patients with CLN2 disease. Brineura is administered into the cerebrospinal fluid (CSF) by infusion via a specific surgically implanted reservoir and catheter in the head (intraventricular access device). Brineura must be administered under sterile conditions to reduce the risk of infections, and treatment should be managed by a health care professional knowledgeable in intraventricular administration. The recommended dose of Brineura in pediatric patients 3 years of age and older is 300 mg administered once every other week by intraventricular infusion, followed by an infusion of electrolytes. The complete Brineura infusion, including the required infusion of intraventricular electrolytes, lasts approximately 4.5 hours. Pre-treatment of patients with antihistamines with or without antipyretics (drugs for prevention or treatment of fever) or corticosteroids is recommended 30 to 60 minutes prior to the start of the infusion.

The efficacy of Brineura was established in a non-randomized, single-arm dose escalation clinical study in 22 symptomatic pediatric patients with CLN2 disease and compared to 42 untreated patients with CLN2 disease from a natural history cohort (an independent historical control group) who were at least 3 years old and had motor or language symptoms. Taking into account age, baseline walking ability and genotype, Brineura-treated patients demonstrated fewer declines in walking ability compared to untreated patients in the natural history cohort.

The safety of Brineura was evaluated in 24 patients with CLN2 disease aged 3 to 8 years who received at least one dose of Brineura in clinical studies. The safety and effectiveness of Brineura have not been established in patients less than 3 years of age.

The most common adverse reactions in patients treated with Brineura include fever, ECG abnormalities including slow heart rate (bradycardia), hypersensitivity, decrease or increase in CSF protein, vomiting, seizures, hematoma (abnormal collection of blood outside of a blood vessel), headache, irritability, increased CSF white blood cell count (pleocytosis), device-related infection, feeling jittery and low blood pressure.

Brineura should not be administered to patients if there are signs of acute intraventricular access device-related complications (e.g., leakage, device failure or signs of device-related infection such as swelling, erythema of the scalp, extravasation of fluid, or bulging of the scalp around or above the intraventricular access device). In case of intraventricular access device complications, health care providers should discontinue infusion of Brineura and refer to the device manufacturer’s labeling for further instructions. Additionally, health care providers should routinely test patient CSF samples to detect device infections. Brineura should also not be used in patients with ventriculoperitoneal shunts (medical devices that relieve pressure on the brain caused by fluid accumulation).

Health care providers should also monitor vital signs (blood pressure, heart rate, etc.) before the infusion starts, periodically during infusion and post-infusion in a health care setting. Health care providers should perform electrocardiogram (ECG) monitoring during infusion in patients with a history of slow heart rate (bradycardia), conduction disorder (impaired progression of electrical impulses through the heart) or structural heart disease (defect or abnormality of the heart), as some patients with CLN2 disease can develop conduction disorders or heart disease. Hypersensitivity reactions have also been reported in Brineura-treated patients. Due to the potential for anaphylaxis, appropriate medical support should be readily available when Brineura is administered. If anaphylaxis occurs, infusion should be immediately discontinued and appropriate treatment should be initiated.

The FDA will require the Brineura manufacturer to further evaluate the safety of Brineura in CLN2 patients below the age of 2 years, including device related adverse events and complications with routine use. In addition, a long-term safety study will assess Brineura treated CLN2 patients for a minimum of 10 years.

The FDA granted this application Priority Review and Breakthrough Therapydesignations. Brineura also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The sponsor is also receiving a Rare Pediatric Disease Priority Review Voucherunder a program intended to encourage development of new drugs and biologics for the prevention and treatment of rare pediatric diseases. A voucher can be redeemed by a sponsor at a later date to receive Priority Review of a subsequent marketing application for a different product. This is the tenth rare pediatric disease priority review voucher issued by the FDA since the program began.

The FDA granted approval of Brineura to BioMarin Pharmaceutical Inc.

////////Brineura, cerliponase alfa, fda 2017, Batten disease, BioMarin Pharmaceutical Inc, Priority Review,  Breakthrough Therapy designations, Orphan Drug designation,

FDA approves first drug Ingrezza (valbenazine) to treat tardive dyskinesia


Valbenazine.svg

Valbenazine

  • Molecular FormulaC24H38N2O4
  • Average mass418.569 Da
(2R,3R,11bR)-3-Isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl L-valinate
(2R,3R,11bR)-9,10-dimethoxy-3-(2-methylpropyl)-1,3,4,6,7,11b-hexahydro-2H-benzo[a]quinolizin-2-yl L-valinate
1025504-45-3 cas
L-Valine, (2R,3R,11bR)-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H-benzo[a]quinolizin-2-yl ester
NBI-98854
Image result for valbenazine
Valbenazine ditosylate. RN: 1639208-54-0. UNII: 5SML1T733B, Molecular Formula, C24-H38-N2-O4.2C7-H8-O3-S, Molecular Weight, 762.9806

(2R,3R,11bR)-9,10-Dimethoxy-3-(2-methylpropyl)-1,3,4,6,7,11b-hexahydro-2H-benzo(a)quinolizin-2-yl L-valinate bis(4-methylbenzenesulfonate)

and

Valbenazine dihydrochloride
1639208-51-7

04/11/2017
The U.S. Food and Drug Administration today approved Ingrezza (valbenazine) capsules to treat adults with tardive dyskinesia. This is the first drug approved by the FDA for this condition.

April 11, 2017

Release

The U.S. Food and Drug Administration today approved Ingrezza (valbenazine) capsules to treat adults with tardive dyskinesia. This is the first drug approved by the FDA for this condition.

Tardive dyskinesia is a neurological disorder characterized by repetitive involuntary movements, usually of the jaw, lips and tongue, such as grimacing, sticking out the tongue and smacking the lips. Some affected people also experience involuntary movement of the extremities or difficulty breathing.

“Tardive dyskinesia can be disabling and can further stigmatize patients with mental illness,” said Mitchell Mathis, M.D., director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research. “Approving the first drug for the treatment of tardive dyskinesia is an important advance for patients suffering with this condition.”

Tardive dyskinesia is a serious side effect sometimes seen in patients who have been treated with antipsychotic medications, especially the older medications, for long periods to treat chronic conditions, such as schizophrenia and bipolar disorder. Tardive dyskinesia can also occur in patients taking antipsychotic medications for depression and certain medications for gastrointestinal disorders and other conditions. It is unclear why some people who take these medications develop tardive dyskinesia yet others do not.

The efficacy of Ingrezza was shown in a clinical trial of 234 participants that compared Ingrezza to placebo. After six weeks, participants who received Ingrezza had improvement in the severity of abnormal involuntary movements compared to those who received placebo.

Ingrezza may cause serious side effects including sleepiness and heart rhythm problems (QT prolongation). Its use should be avoided in patients with congenital long QT syndrome or with abnormal heartbeats associated with a prolonged QT interval. Those taking Ingrezza should not drive or operate heavy machinery or do other dangerous activities until it is known how the drug affects them.

The FDA granted this application Fast Track, Priority Review and Breakthrough Therapy designations.

The FDA granted approval of Ingrezza to Neurocrine Biosciences, Inc.

Valbenazine (INN,[1]:114 proposed trade name Ingrezza) is the first drug approved by the FDA[2] for use in the treatment of tardive dyskinesia.[3][4] Clinical trials are underway to evaluate its efficacy in the treatment of Tourette’s syndrome.[5][6] It acts as a vesicular monoamine transporter 2 (VMAT2) inhibitor.[7]

Pharmacology

Mechanism of action

Valbenazine is known to cause reversible reduction of dopamine release by selectively inhibiting pre-synaptic human vesicular monoamine transporter type 2 (VMAT2). In vitro, valbenazine shows great selectivity for VMAT2 and little to no affinity for VMAT1 or other monoamine receptors.[8] Although the exact cause of tardive dyskinsia is unknown, it is hypothesized that it may result from neuroleptic-induced dopamine hypersensitivity.[9] By selectively reducing the ability of VMAT2 to load dopamine into synaptic vesicles,[10] the drug reduces overall levels of available dopamine in the synaptic cleft, ideally alleviating the symptoms associated with dopamine hypersensitivity. The importance of valbenazine selectivity inhibiting VMAT2 over other monoamine transporters is that VMAT2 is mainly involved with the transport of dopamine, and to a much lesser extent other monoamines such as norepinephrine, serotonin, and histamine. This selectivity is likely to reduce the likelihood of “off-target” adverse effects which may result from the upstream inhibition of these other monoamines.[11]

Society and culture

Commercial aspects

Valbenazine is produced by Neurocrine Biosciences, a company based in San Diego. In addition to the late-stage clinical trials studying valbenazine, Neurocrine Biosciences (partnered with AbbVie Inc.) also has another product, elagolix (a hormone antagonist), undergoing clinical trials.[12] Following the initiation of these trials, on 5 May 2016 Neurocrine reported revenues of $15 million for the first quarter of 2016.[13] The company now focuses on filing the valbenazine new drug application as they prepare for the commercial launch of the drug for the treatment of tardive dyskinesia.Neurocrine’s expenses have risen steadily since May 2015, primarily due to the pre-commercialization activities for valbenazine. [14]

Intellectual property

While Neurocrine Biosciences does not currently hold a final patent for valbenazine or elagolix, they do hold a patent for the VMAT2 inhibitor [9,10-dimethoxy-3-(2-methylpropyl)-1H,2H,3H,4H,6H,7H,11bH-pyrido-[2,1-a]isoquinolin-2-yl]methanol and related compounds, which includes valbenazine.[15]

ChemSpider 2D Image | Valbenazine | C24H38N2O4

References

  1.  “International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 71” (PDF). World Health Organization. Retrieved 18 November 2016.
  2.  Newswire, MultiVu – PR. “Neurocrine Announces FDA Approval of INGREZZA TM (valbenazine) Capsules as the First and Only Approved Treatment for Adults with Tardive Dyskinesia (TD)”. Multivu. Retrieved 2017-04-11.
  3.  Ben Adams (Aug 30, 2016). “Neurocrine submits valbenazine NDA early, set for 2017 approval”. fiercebiotech.com.
  4.  “Safety and Tolerability Study of NBI-98854 for the Treatment of Tardive Dyskinesia – Full Text View – ClinicalTrials.gov”. clinicaltrials.gov. Retrieved 2016-11-13.
  5. Jump up^ “Tourette Syndrome Clinical Trials | Neurocrine Biosciences”. http://www.neurocrine.com. Retrieved 2016-11-13.
  6. Jump up^ “Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome – Full Text View – ClinicalTrials.gov”. clinicaltrials.gov. Retrieved 2016-11-13.
  7. Jump up^ O’Brien, C. F.; Jimenez, R; Hauser, R. A.; Factor, S. A.; Burke, J; Mandri, D; Castro-Gayol, J. C. (2015). “NBI-98854, a selective monoamine transport inhibitor for the treatment of tardive dyskinesia: A randomized, double-blind, placebo-controlled study”. Movement Disorders. 30 (12): 1681–7. doi:10.1002/mds.26330. PMC 5049616Freely accessible. PMID 26346941.
  8. Jump up^ “NBI-98854 – VMAT2 Inhibitor | Tics in Children Treatment | Neurocrine Biosciences”. http://www.neurocrine.com. Retrieved 2016-11-13.
  9. Jump up^ “tardive-dyskinesia”. http://www.priory.com. Retrieved 2016-11-13.
  10. Jump up^ Purves, Dale, et al. Neuroscience. Sinauer Associates. 087893646
  11.  “NBIX: NDA for Valbenazine in Tardive Dyskinesia to be Filed in 2016…”. Retrieved 2016-11-13.
  12.  “Endocrine & Movement Disorder R&D | About | Neurocrine Biosciences”. http://www.neurocrine.com. Retrieved 2016-11-14.
  13.  “NBIX: NDA for Valbenazine in Tardive Dyskinesia to be Filed in 2016…”. Retrieved 2016-11-20.
  14.  “Press Release | Neurocrine Biosciences, Inc.”. phoenix.corporate-ir.net. Retrieved 2016-11-20.
  15.  “[9,10-dimethoxy-3-(2-methylpropyl)-1h,2h,3h,4h,6h,7h,11bh-pyrido-[2,1-a]isoquinolin-2-yl]methanol And Compounds, Compositions And Methods Relating Thereto”. Retrieved 2016-11-20.
1 to 3 of 3
Patent ID Patent Title Submitted Date Granted Date
US8039627 SUBSTITUTED 3-ISOBUTYL-9, 10-DIMETHOXY-1, 3, 4, 6, 7, 11B-HEXAHYDRO-2H-PYRIDO[2, 1-A]ISOQUINOLIN-2-OL COMPOUNDS AND METHODS RELATING THERETO 2008-07-10 2011-10-18
US8357697 Substituted 3-isobutyl-9, 10-dimethoxy-1, 3, 4, 6, 7, 11b-hexahydro-2H-pyrido[2, 1-A]isoquinolin-2-ol compounds and methods relating thereto 2011-09-20 2013-01-22
US2016068526 BENZOQUINOLONE INHIBITORS OF VMAT2 2014-01-28 2016-03-10
Valbenazine
Valbenazine.svgImage result for valbenazine
Clinical data
ATC code
  • none
Legal status
Legal status
  • Investigational
Identifiers
Synonyms NBI-98854
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C24H38N2O4
Molar mass 418.58 g·mol−1
3D model (Jmol)
////////fda 2017, Ingrezza, valbenazine, tardive dyskinesia, Fast Track, Priority Review ,  Breakthrough Therapy designations, 1025504-45-3, NBI-98854, 
%d bloggers like this: