FLAGS AND HITS
DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO
FACEBOOK
...................................................................Join me on twitter
..................................................................Join me on google plus
GoogleplusMYSELF
Otsuka and Lundbeck’s Once-Monthly Abilify Maintena(R) (Aripiprazole) Now Approved in Europe
Otsuka and Lundbeck’s Once-Monthly Abilify Maintena(R) (Aripiprazole) Now Approved in Europe for Maintenance Treatment of Schizophrenia in Adult Patients Stabilized with Oral Aripiprazole
do not forget to see my old blog post, contains synthesis
Preventing relapse is critical in the treatment of schizophrenia. Pivotal
studies, that supported the EU submission, demonstrate that Abilify
Maintena can reduce the risk of relapse relative to placebo and is
non-inferior to oral aripiprazole in patients with schizophrenia1,2
-- The approval of Abilify Maintena now provides patients with schizophrenia
access to a once-monthly formulation with established efficacy together
with a tolerability profile that is comparable to that of oral ABILIFY(R)
(aripiprazole)2
-- At the end of the randomized, double-blind treatment phase in one of the
pivotal trials, 93 percent of patients reported being extremely, very or
somewhat satisfied with Abilify Maintena treatment3
-- Abilify Maintena is the only dopamine D2 partial agonist in a
once-monthly, injectable form to receive marketing authorization in
Europe for maintenance treatment of schizophrenia
-- Abilify Maintena will be the first commercialized product in Europe from
the global alliance between Otsuka and Lundbeck which is focused on
developing Central Nervous System (CNS) therapies worldwide
TOKYO & COPENHAGEN, Denmark--(BUSINESS WIRE)--November 21, 2013--
Otsuka Pharmaceutical Co., Ltd. (Otsuka) and H. Lundbeck A/S (Lundbeck) today announced marketing authorization approval from the European Commission for Abilify Maintena (aripiprazole), an intramuscular (IM) once-monthly injectable formulation for maintenance treatment of schizophrenia in adult patients stabilized with oral aripiprazole.
Abilify Maintena reduces the risk of relapse relative to placebo over the long-term and provides effective treatment of schizophrenia.(1,2) It has a tolerability profile similar to oral aripiprazole(1) , and demonstrated statistically significant benefits on patients’ personal and social functioning as compared to placebo.(1,4) 93 percent of patients treated with Abilify Maintena were extremely, very or somewhat satisfied with their treatment at the end of the double-blind treatment phase.(4)
“We strongly believe the schizophrenia community will welcome the availability of Abilify Maintena to help improve outcomes for patients living with schizophrenia. As a company, our focus is to develop treatments to help protect against relapse and preserve brain function,” said Ole Vahlgren, CEO & President, Otsuka Europe. “We must partner with health care professionals and caregivers to help patients get the best treatments that focus on reducing the risk of relapse.”
“Studies have shown that the early use of long-acting injectables can prevent a person with schizophrenia from experiencing a relapse,”(5) said Ole Chrintz, SVP International Markets & Europe, Lundbeck. “Efficacy is important, but a treatment for a chronic condition such as schizophrenia also needs to be well tolerated so patients will stay on it over the long-term. We believe Abilify Maintena meets this need.”(1,2,3)
About the Studies
The efficacy of Abilify Maintena was demonstrated in two double-blind, Phase III, randomized trials. The safety profile for Abilify Maintena was demonstrated to be similar to that of oral ABILIFY. The most frequently observed adverse drug reactions (ADRs) reported in >=5 percent of patients in two double-blind controlled clinical trials of Abilify Maintena were weight increases (9.0 percent), akathisia (7.9 percent), insomnia (5.8 percent), and injection site pain (5.1 percent).(1,2)
About Abilify Maintena
Abilify Maintena is the only dopamine D2 partial agonist in once-monthly, injectable form to receive marketing authorization for maintenance treatment in schizophrenia. Physicians now have an alternative treatment option, with a tolerability profile comparable to the well-established oral ABILIFY, to address the on-going need to reduce the risk of relapse in patients with schizophrenia.
The European label states that Abilify Maintena is a powder and solvent for prolonged-release suspension for intra-muscular (IM) injection. It is a once-monthly formulation of aripiprazole in a sterile lyophilized powder that is reconstituted with sterile water. Abilify Maintena is indicated for maintenance treatment of schizophrenia in adult patients stabilized with oral aripiprazole.
After the first injection, treatment with 10 mg to 20 mg oral aripiprazole should be continued for 14 consecutive days to maintain therapeutic aripiprazole concentrations during initiation of therapy.
About Schizophrenia and Disease Relapse
Schizophrenia is a disease characterized by a distortion in the process of thinking and of emotional responsiveness. It most commonly manifests as hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and is accompanied by significant social or occupational dysfunction. Onset of symptoms typically occurs in young adulthood, and the condition is chronic, often requiring lifelong treatment to mitigate symptoms.
Relapse of schizophrenia refers to an exacerbation or acute psychotic break that is characterised primarily by the emergence of positive symptoms such as hallucinations, delusions and disordered thinking.(6)
Relapse can occur when a patient no longer responds to antipsychotic medication, does not take the medication as prescribed, or stops taking their medication altogether. There are many reasons patients stop taking their medication, including poor insight about their illness, side effects from current treatments, complicated medication regimen or lack of support from family.(7) Abilify Maintena is able to significantly reduce the risk of relapse in patients with schizophrenia.(1)
It has been estimated that schizophrenia affects approximately one percent of the adult population in the U.S. and Europe, and approximately 24 million people worldwide.(8,9) In Europe there are approximately 4.4 million adults with schizophrenia,(10) prevalent equally in both genders.(11,12) While there is no cure for the disease, symptoms and risk of relapse can be managed in most patients with appropriate antipsychotic treatment. However, when the disease is not managed, patients are at increased risk of disease relapse, which can cause the re-emergence or worsening of psychotic symptoms.(13)
Schizophrenia places a significant burden on society. It is regarded among the most financially costly illnesses and is according to the World Health Organization (WHO), the 8(th) leading cause of DALYs (lost healthy years) worldwide among patients between the age of 15-44.(11) With 50 percent of patients not receiving appropriate care and 80 percent of patients relapsing within the first 5 years,(14) there is a significant unmet need to be addressed in schizophrenia.
About the Lundbeck and Otsuka Global Alliance
Lundbeck and Otsuka established a global alliance in November 2011 to bring to bear their considerable experience and resources in the CNS area to introduce next-generation treatments for conditions such as schizophrenia, depression, Alzheimer’s disease and alcohol dependency.
About Otsuka Pharmaceutical Co., Ltd.
Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: ‘Otsuka-people creating new products for better health worldwide.’ Otsuka researches, develops, manufactures and markets innovative and original products, with a focus on pharmaceutical products for the treatment of diseases and nutraceutical products for the maintenance of everyday health.
In pharmaceuticals, Otsuka is a leading firm in the challenging area of mental health and also has research programs for several under-addressed diseases including tuberculosis, a significant global public health issue. These commitments illustrate more powerfully than words how Otsuka is a “big venture” company at heart, applying a youthful spirit of creativity in everything it does.
Otsuka is a wholly owned subsidiary of Otsuka Holdings Co., Ltd., the holding company for the Otsuka Group. The chairman Akihiko Otsuka is the third generation of Otsuka family members to lead the business, whose origins date from 1921. The Otsuka Group employs approximately 42,000 people globally and its products are available in more than 80 countries worldwide. Consolidated sales were approximately EUR10 billion or USD 13 billion for fiscal year 2012 (4/1/2012-3/31/2013). Otsuka Pharmaceutical welcomes you to visit its global website at https://www.otsuka.co.jp/en/
About H. Lundbeck A/S
Lundbeck is a global pharmaceutical company highly committed to improving the quality of life of people living with brain diseases. For this purpose, Lundbeck is engaged in the entire value chain throughout research, development, production, marketing and sales of pharmaceuticals across the world. The company’s products are targeted at disorders such as depression and anxiety, psychotic disorders, epilepsy, Huntington’s, Alzheimer’s and Parkinson’s diseases. Lundbeck’s pipeline consists of several mid- to late-stage development programmes.
Lundbeck employs more than 5,800 people worldwide, 2,000 of whom are based in Denmark. We have research in 57 countries and our products are registered in more than 100 countries. We have research centers in Denmark, China and the United States and production facilities in Italy, France, Mexico, China and Denmark. Lundbeck generated revenue of approximately DKK 15 billion in 2012. For additional information, we encourage you to visit our corporate site http://www.lundbeck.com.
REFERENCES:
1. Kane, JM et al. Aripiprazole intramuscular depot as maintenance treatment in
patients with schizophrenia: a 52-week, multicenter, randomized,
double-blind, placebo-controlled study. J Clin Psychiatry 2012;73(5):617-62
2. Fleischhacker WW, Sanchez R, Perry PP, et al. Aripiprazole once-monthly for
the treatment of schizophrenia: a double-blind, randomized, non-inferiority
study vs. oral aripiprazole. Annual Meeting of the American Psychiatric
Association, 18--22 May, 2013 (poster).
3. Sanchez R, et al. Patient-reported Outcomes with
Aripiprazole-Intramuscular-Depot for Long-term Maintenance Treatment in
Schiziphrenia. NR6-42 2012 (poster)
4. Carson WH, Perry P, Sanchez R, et al. Effects of a Once-Monthly Formulation
of Aripiprazole on Secondary Efficacy Outcomes in Maintenance Treatment of
Schizophrenia. Institute on Psychiatric Services meeting, October 4--7, 2012
(Poster)
5. Long-acting injectable antipsychotics in the treatment of schizophrenia:
their role in relapse prevention. Agid O, et al. Expert Opin. Pharmacother.
(2010) 11(14):2301-2317
6. Ayuso-Gutierrez JL, del Rio Vega JM. Factors influencing relapse in the
long-term course of schizophrenia. Schizophr Res. 1997; 28(2-3): 199-206
7. Baloush-Kleinman V, et al. Adherence to antipsychotic drug treatment in
early-episode schizophrenia: a six-month naturalistic follow-up study.
Schizophr Res. 2011;130(1-3):176-81.
8. National Institute of Mental Health (NIMH). Health Topics: Statistics.
Available at http://www.nimh.nih.gov/statistics/1SCHIZ.shtml. Accessed
October 22, 2013
9. World Health Organization (WHO). Schizophrenia Fact Sheet. 2010. Available
at: http://www.who.int/mental_health/management/schizophrenia/en/. Accessed
October 22, 2013.
10. World Health Organization (WHO) The global burden of disease:2004 update
(2008)
11. National Institute of Mental Health (NIMH). The Numbers Count: Mental
Disorders in America. 2010. Available at
http://www.nimh.nih.gov/health/publications/the-numbers-count-mental-disorde
rs-in-America/index.shtml#Schizophrenia. Accessed October 22, 2013
12. Regier DA, et al. The de facto US mental and addictive disorders service
system. Epidemiologic catchment area prospective 1-year prevalence rates of
disorders and services. Arch Gen Psychiatry. 1993;50(2):85-94.
13. American Psychiatric Association. Practice guideline for the treatment of
patients with schizophrenia. Second edition. 2004. Available at
http://psychiatryonline.org/content.aspx?bookid=28§ionid=1665359.
Accessed October 28, 2013
14. Robinson D, et al. Predictors of relapse following response from a first
episode of schizophrenia or schizoaffective disorder. Arch Gen Psychiatry.
1999;56(3):241-247
read my earlier blog post
https://newdrugapprovals.wordpress.com/2013/02/07/the-european-medicines-agency-ema-approves-otsukas-aripiprazole-abilify-for-the-treatment-of-moderate-to-severe-manic-episodes-in-bipolar-i-disorder-in-adolescents/
Bayer, Onyx win early FDA OK for Nexavar (sorafenib) in thyroid cancer
The U.S. Food and Drug Administration said on Friday it has expanded the approved use of the cancer drug Nexavar to include late-stage differentiated thyroid cancer.
Differentiated thyroid cancer is the most common type of thyroid cancer, the FDA said. The National Cancer Institute estimates that 60,220 people in the United States will be diagnosed with it and 1,850 will die from the disease in 2013.
The drug, made by Germany’s Bayer AG and Onyx Pharmaceuticals, is already approved to treat advanced kidney cancer and liver cancer that cannot be surgically removed. Onyx was acquired by Amgen Inc earlier this year.
READ ABOUT SORAFENIB IN MY EARLIER BLOGPOST
https://newdrugapprovals.wordpress.com/2013/07/16/nexavar-sorafenib/
SCRIP Awards 2013 -Best Company in an Emerging Market – Dr Reddy’s Laboratories – India, Novartis’s Bexsero, Best New Drug
The SCRIP Awards 2013 celebrated achievements in the global biopharma industry last night at the Lancaster, London.
Hosted by Justin Webb, the evening was a fantastic mix of dining, entertainment and awards.
Among the winners were:
- Novartis’s Bexsero, Best New Drug
- Genmab, Biotech Company of the Year
- Regeneron Pharmaceuticals and Sanofi’s Phase IIa study dupilumab in asthma, Clinical Advance of the Year
You can view the full roll of honour by clicking on the button below.
It was a great night and we would like to thank all those who entered and attended this year’s awards.
Finally congratulations to our winners and a huge thanks to our sponsors for helping us make it such a fantastic success.
Don’t forget to check our website in the next couple of days for all the pictures from the night.
2013 Winners
Best Company in an Emerging Market – Sponsored by Clinigen Group
- Dr Reddy’s Laboratories – India
Best Technological Development in Clinical Trials
- Quintiles’s Infosario Safety
Best Partnership Alliance
- AstraZeneca with Bristol-Myers Squibb and Amylin in diabetes
Financing Deal of the Year
- Mesoblast’s equity financing of Aus$170m
Best Advance in an Emerging Market
- Novartis’s Jian Kang Kuai Che Healthcare Project in China
Clinical Advance of the Year – Sponsored by Quintiles
- Regeneron Pharmaceuticals and Sanofi’s Phase IIa study dupilumab in in asthma
Licensing Deal of the Year – Sponsored by Hume Brophy
- AstraZeneca and Horizon Discovery for the development and commercialization of the HD-001 kinase target program for multiple cancer types
Executive of the Year
- Roch Doliveux, chairman and chief executive officer of UCB
Biotech Company of the Year
- Genmab
Best Contract Research Organization
- Quintiles
Management Team of the Year
- Regeneron Pharmaceuticals’ CEO Leonard S Schleifer and CSO George D Yancopoulos
Best New Drug – Sponsored by INC Research
- Novartis’ Bexsero (meningococcal group B vaccine)
Pharma Company of the Year – Sponsored by ICON
- Astellas
Lifetime Achievement Award
- Prof Dr Désiré Collen
…….read about bexero at
DR ANTHONY MELVIN CRASTO Ph.D
Late-stage success for Sanofi/Regeneron RA drug sarilumab
SARILUMAB
PRONUNCIATION sar il’ ue mab
THERAPEUTIC CLAIM Treatment of rheumatoid arthritis and
ankylosing spondylitis
CHEMICAL NAMES
1. Immunoglobulin G1, anti-(human interleukin 6 receptor α) (human REGN88 heavy
chain), disulfide with human REGN88 light chain, dimer
2. Immunoglobulin G1, anti-(human interleukin-6 receptor subunit alpha (IL-6RA,
membrane glycoprotein 80, CD126)); human monoclonal RGN88 γ1 heavy chain (219-
214′)-disulfide with human monoclonal RGN88 κ light chain dimer (225-225”:228-
228”)-bisdisulfide
MOLECULAR FORMULA C6388H9918N1718O1998S44
MOLECULAR WEIGHT 144.13 kDa
SPONSOR Regeneron Pharmaceuticals, Inc.
CODE DESIGNATION REGN88, SAR153191
CAS REGISTRY NUMBER 1189541-98-7
sarilumab
Sarilumab (REGN88/SAR153191) is a fully-human monoclonal antibody directed against the IL-6 receptor (IL-6R). Sarilumab is a subcutaneously delivered inhibitor of IL-6 signaling, which binds with high affinity to the IL-6 receptor. It blocks the binding of IL-6 to its receptor and interrupts the resultant cytokine-mediated inflammatory signaling.
Sanofi and Regeneron’s investigational rheumatoid arthritis drug sarilumab has succeeded in a late-stage trial.
The year-long Phase III study enrolled 1,200 patients with active, moderate-to-severe RA who were inadequate responders to methotrexate. Patients were randomised to one of three subcutaneous treatment groups, all in combination with MTX and dosed every other week – sarilumab 200mg, 150mg or placebo.http://www.pharmatimes.com/Article/13-11-22/Late-stage_success_for_Sanofi_Regeneron_RA_drug.aspx
Sarilumab is a human monoclonal antibody against the interleukin-6 receptor.
Regeneron and Sanofi are currently co-developing the drug for the treatment of rheumatoid arthritis, for which it is in phase III trials. Development inankylosing spondylitis has been suspended after the drug failed to show clinical benefit over methotrexate in a phase II trial.[1][2]
On May 15th, 2013, both companies announced that 2 new trials were starting (COMPARE and ASCERTAIN) and the first patients had already been enrolled.[3]
On November 22nd, 2013, both companies On May 15th, 2013, both companies announced positive phase 3 results for the RA-MOBILITY trial
- “Statement On A Nonproprietary Name Adopted By The USAN Council: Sarilumab”. American Medical Association.
- http://investor.regeneron.com/releasedetail.cfm?releaseid=590869
- http://en.sanofi.com/Images/33027_20130515_sari_en.pdf
fully human monoclonal antibody directed against the interleukin-6 receptor (IL-6R) in combination with methotrexate (MTX) therapy improved disease signs and symptoms as well as physical functionw while inhibiting progression of joint damage in adults with RA who saw little improvement through MTX therapy alone.
Sarilumab met all three primary endpoints of the 52-week SARIL-RA-MOBILITY Phase III trial by demonstrating clinically relevant and statistically significant improvements compared to the placebo group in the two groups treated with the drug candidate. The trial enrolled about 1,200 patients with active, moderate-to-severe rheumatoid arthritis who were inadequate responders to MTX therapy.
Of patients treated with the 200 mg dose of sarilumab plus MTX, 66% saw improvement in signs and symptoms of RA at 24 weeks, as measured by the American College of Rheumatology score of at-least 20% improvement. The percentage dipped to 58% of sarilumab 150 mg dose patients, and 33% of placebo patients.
Sarilumab 200 mg patients showed the least progression of structural damage after 52 weeks, registering a 0.25 change in the modified Van der Heijde total Sharp score. That contrasts with scores of 0.90 in patients taking sarilumab 150 mg, and 2.78 in the placebo group.
In addition, sarilumab 200 mg patients showed improvement in physical function, as measured by change from baseline in the Health Assessment Question-Disability at week 16. However, the companies did not quantify those results in their announcement. Sanofi and Regeneron said additional analyses of efficacy and safety data from SARIL-RA-MOBILITY will be presented “at a future medical conference.”
“We are encouraged by these Phase III results and the impact sarilumab demonstrated on inhibition of progression of structural damage assessed radiographically in this study,” Tanya M. Momtahen, Sanofi’s sarilumab global project head, said in a statement.
Sarilumab—known as SAR153191 and REGN88—blocks the binding of IL-6 to its receptor and interrupts the resultant cytokine-mediated inflammatory signaling characteristic of RA. Sarilumab was developed using Regeneron’s VelocImmune® antibody technology.
The positive results continue what has been mostly strong success in clinical trials for the partners, whose development collaborations include alirocumab (REGN727), dupilumab (REGN668), and enoticumab (REGN421). Alirocumab is a PCSK9 antibody being evaluated for its ability to manage LDL cholesterol, including in people who do not get to their target LDL levels using statin medicines alone. Dupilumab is an antibody to the receptors for interleukin-4 and interleukin-13 under evaluation in atopic dermatitis and eosinophilic asthma. Enoticumab is a fully human monoclonal antibody to delta-like ligand-4 (Dll4) now in Phase I study for advanced malignancies.
On its own, however, Sanofi’s R&D efforts have shown more mixed results, with the pharma giant earlier this month ending development of cancer drug candidate fedratinib (SAR302503) after it was placed on clinical hold by the FDA following reports that some patients in clinical trials developed symptoms consistent with Wernicke’s encephalopathy. Another cancer compound, iniparib, had its development halted earlier this year after a disappointing Phase III trial.
European Commission Approves Gilead’s VitektaTM, an Integrase Inhibitor for the Treatment of HIV-1 Infection
Elvitegravir
697761-98-1 CAS
FOSTER CITY, Calif.–(BUSINESS WIRE)–Nov. 18, 2013– Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the European Commission has granted marketing authorization for VitektaTM (elvitegravir 85 mg and 150 mg) tablets, an integrase inhibitor for the treatment of HIV-1 infection in adults without known mutations associated with resistance to elvitegravir. Vitekta is indicated for use as part of HIV treatment regimens that include a ritonavir-boosted protease inhibitor.http://www.pharmalive.com/eu-oks-gileads-vitekta Vitekta interferes with HIV replication by blocking the virus from integrating into the genetic material of human cells. In clinical trials, Vitekta was effective in suppressing HIV among patients with drug-resistant strains of HIV.http://www.pharmalive.com/eu-oks-gileads-vitekta
Elvitegravir (EVG, formerly GS-9137) is a drug used for the treatment of HIV infection. It acts as an integrase inhibitor. It was developed[1] by the pharmaceutical company Gilead Sciences, which licensed EVG from Japan Tobacco in March 2008.[2][3][4] The drug gained approval by U.S. Food and Drug Administration on August 27, 2012 for use in adult patients starting HIV treatment for the first time as part of the fixed dose combination known as Stribild.[5]
According to the results of the phase II clinical trial, patients taking once-daily elvitegravir boosted by ritonavir had greater reductions in viral load after 24 weeks compared to individuals randomized to receive a ritonavir-boosted protease inhibitor.[6]
Human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired immunodeficiency disease syndrome (AIDS). After over 26 years of efforts, there is still not a therapeutic cure or an effective vaccine against HIV/AIDS. The clinical management of HIV-1 infected people largely relies on antiretroviral therapy (ART). Although highly active antiretroviral therapy (HAART) has provided an effective way to treat AIDS patients, the huge burden of ART in developing countries, together with the increasing incidence of drug resistant viruses among treated people, calls for continuous efforts for the development of anti-HIV-1 drugs. Currently, four classes of over 30 licensed antiretrovirals (ARVs) and combination regimens of these ARVs are in use clinically including: reverse transcriptase inhibitors (RTIs) (e.g. nucleoside reverse transcriptase inhibitors, NRTIs; and non-nucleoside reverse transcriptase inhibitors, NNRTIs), protease inhibitors (PIs), integrase inhibitors and entry inhibitors (e.g. fusion inhibitors and CCR5 antagonists).
- Gilead Press Release Phase III Clinical Trial of Elvitegravir July 22, 2008
- Gilead Press Release Gilead and Japan Tobacco Sign Licensing Agreement for Novel HIV Integrase Inhibitor March 22, 2008
- Shimura K, Kodama E, Sakagami Y, et al. (2007). “Broad Anti-Retroviral Activity and Resistance Profile of a Novel Human Immunodeficiency Virus Integrase Inhibitor, Elvitegravir (JTK-303/GS-9137)”. J Virol 82 (2): 764. doi:10.1128/JVI.01534-07. PMC 2224569. PMID 17977962.
- Stellbrink HJ (2007). “Antiviral drugs in the treatment of AIDS: what is in the pipeline ?”. Eur. J. Med. Res. 12 (9): 483–95. PMID 17933730.
- Sax, P. E.; Dejesus, E.; Mills, A.; Zolopa, A.; Cohen, C.; Wohl, D.; Gallant, J. E.; Liu, H. C.; Zhong, L.; Yale, K.; White, K.; Kearney, B. P.; Szwarcberg, J.; Quirk, E.; Cheng, A. K.; Gs-Us-236-0102 Study, T. (2012). “Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: A randomised, double-blind, phase 3 trial, analysis of results after 48 weeks”.The Lancet 379 (9835): 2439–2448. doi:10.1016/S0140-6736(12)60917-9. PMID 22748591. edit
- Thaczuk, Derek and Carter, Michael. ICAAC: Best response to elvitegravir seen when used with T-20 and other active agents Aidsmap.com. 19 Sept. 2007.
The life cycle of HIV-1. 1. HIV-1 gp120 binds to CD4 and co-receptor CCR5/CXCR4 on target cell; 2. HIV-1 gp41 mediates fusion with target cell; 3. Nucleocapsid containing viral genome and enzymes enters cells; 4. Viral genome and enzymes are released; 5. Viral reverse transcriptase catalyzes reverse transcription of ssRNA, forming RNA-DNA hybrids; 6. RNA template is degraded by ribonuclease H followed by the synthesis of HIV dsDNA; 7. Viral dsDNA is transported into the nucleus and integrated into the host chromosomal DNA by the viral integrase enzyme; 8. Transcription of proviral DNA into genomic ssRNA and mRNAs formation after processing; 9. Viral RNA is exported to cytoplasm; 10. Synthesis of viral precursor proteins under the catalysis of host-cell ribosomes; 11. Viral protease cleaves the precursors into viral proteins; 12. HIV ssRNA and proteins assemble under host cell membrane, into which gp120 and gp41 are inserted; 13. Membrane of host-cell buds out, forming the viral envelope; 14. Matured viral particle is released
Elvitegravir, also known as GS 9137 or JTK 303, is an investigational new drug and a novel oral integrase inhibitor that is being evaluated for the treatment of HIV-1 infection. After HIVs genetic material is deposited inside a cell, its RNA must be converted (reverse transcribed) into DNA. A viral enzyme called integrase then helps to hide HIVs DNA inside the cell’s DNA. Once this happens, the cell can begin producing genetic material for new viruses. Integrase inhibitors, such as elvitegravir, are designed to block the activity of the integrase enzyme and to prevent HIV DNA from entering healthy cell DNA. Elvitegravir has the chemical name: 6-(3-chloro-2-fluorobenzyl)-1-[(S)-1 -hydroxy -methyl-2- methylpropyl]-7-methoxy-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid and has the following structural formula:
WO 2000040561 , WO 2000040563 and WO 2001098275 disclose 4-oxo-1 , 4-dihydro-3- quinoline which is useful as antiviral agents. WO2004046115 provides certain 4- oxoquinoline compounds that are useful as HIV Integrase inhibitors.
US 7176220 patent discloses elvitegravir, solvate, stereoisomer, tautomer, pharmaceutically acceptable salt thereof or pharmaceutical composition containing them and their method of treatment. The chemistry involved in the above said patent is depicted below in the Scheme A. Scheme-A
Toluene, DIPEA
SOCl2 ,COCl (S)-(+)-Valinol
Toluene
,4-Difluoro-5-iodo- benzoic acid
THF
dichlorobis(triphenylphosphine)
palladium argon stream,
Elvitegravir Form ] Elvitegravir (residue) US 7635704 patent discloses certain specific crystalline forms of elvitegravir. The specific crystalline forms are reported to have superior physical and chemical stability compared to other physical forms of the compound. Further, process for the preparation of elvitegravir also disclosed and is depicted below in the Scheme B. The given processes involve the isolation of the intermediates at almost all the stages.
Scheme B
2,
–
Zn THF,
CK Br THF CU “ZnBr dιchlorobis(trιphenylphos
phine)palladium
Elvitegravir WO 2007102499 discloses a compound which is useful as an intermediate for the synthesis of an anti-HIV agent having an integrase-inhibiting activity; a process for production of the compound; and a process for production of an anti-HIV agent using the intermediate.
WO 2009036161 also discloses synthetic processes and synthetic intermediates that can be used to prepare 4-oxoquinolone compounds having useful integrase inhibiting properties.
The said processes are tedious in making and the purity of the final compound is affected because of the number of steps, their isolation, purification etc., thus, there is a need for new synthetic methods for producing elvitegravir which process is cost effective, easy to practice, increase the yield and purity of the final compound, or that eliminate the use of toxic or costly reagents.
US Patent No 7176220 discloses Elvitegravir, solvate, stereoisomer, tautomer, pharmaceutically acceptable salt thereof or pharmaceutical composition containing them and ■ their method of treatment. US Patent No 7635704 discloses Elvitegravir Form II, Form III and processes for their preparation. The process for the preparation of Form Il disclosed in the said patent is mainly by three methods – a) dissolution of Elvitegravir followed by seeding with Form II, b) recrystallisation of Elvitegravir, and c) anti-solvent method.
The process for the preparation of Form III in the said patent is mainly by three methods – a) dissolution of Form Il in isobutyl acetate by heating followed by cooling the reaction mass, b) dissolution of Form Il in isobutyl acetate by heating followed by seeding with Form III, and c) dissolving Form Il in 2-propanol followed by seeding with Form III.
Amorphous materials are becoming more prevalent in the pharmaceutical industry. In order to overcome the solubility and potential bioavailability issues, amorphous solid forms are becoming front-runners. Of special importance is the distinction between amorphous and crystalline forms, as they have differing implications on drug substance stability, as well as drug product stability and efficacy.
An estimated 50% of all drug molecules used in medicinal therapy are administered as salts. A drug substance often has certain suboptimal physicochemical or biopharmaceutical properties that can be overcome by pairing a basic or acidic drug molecule with a counter- ion to create a salt version of the drug. The process is a simple way to modify the properties of a drug with ionizable functional groups to overcome undesirable features of the parent drug. Salt forms of drugs have a large effect on the drugs’ quality, safety, and performance. The properties of salt-forming species significantly affect the pharmaceutical properties of a drug and can greatly benefit chemists and formulators in various facets of drug discovery and development.
chemical synthesis from a carboxylic acid 1 starts after conversion to the acid chloride iodide NIS 2 , and with three condensation 4 . 4 and the amino alcohol 5 addition-elimination reaction occurs 6 , 6 off under alkaline conditions with TBS protected hydroxy get the ring 7 , 7 and zinc reagent 8 Negishi coupling occurs to get 9 , the last 9 hydrolysis and methoxylated
Elvitegravir dimer impurity, WO2011004389A2
Isolation of 1-[(2S)-1-({3-carboxy-6-(3-chloro-2-fluorobenzyl)-1 -[(2S)-I- hydroxy-3-methylbutan-2-yl]-4-oxo-1 , 4-dihydroquinolin-7-yl}oxy)-3- methylbutan-2-yl 6-(3-chloro-2-fluorobenzyl)-7-methoxy-4-oxo-1 , 4-dihydroquinoline-3-carboxylic acid (elvitegravir dimer impurity, 13)
After isolation of the elvitegravir from the mixture of ethyl acetate-hexane, solvent from the filtrate was removed under reduced pressure. The resultant residue purified by column chromatography using a mixture of ethyl acetate-hexane (gradient, 20-80% EtOAc in hexane) as an eluent. Upon concentration of the required fractions, a thick solid was obtained which was further purified on slurry washing with ethyl acetate to get pure elvitegravir dimer impurity (13). The 1H-NMR, 13C-NMR and mass spectral data complies with proposed structure.
1H-NMR (DMSO-Cf6, 300 MHz, ppm) – δ 0.79 (m, d=6.3 Hz, 6H, 20 & 2O’)\ 1.18 & 1.20 (d, J=6.3 Hz & J=6.2 Hz, 6H, 21 & 21′)1, 2.42-2.49 (m, 2H, 19 & 19′), 3.81-3.89 (m, 3H, T & 17’Ha), 3.94-4.01 (m, 1 H, 17’Hb), 4.01 (s, 3H, 23), 4.11 (s, 2H, 7), 4.83-4.85 (m, 3H, 17 & 18′), 5.22 (t, J=4.7 Hz, 1H, OH), 5.41-5.44 (m, 1 H, 18), 6.73-6.78 (t, J=7.1 Hz, 1 H, 11)1‘ 2, 6.92-6.98 (t, J=8.0 Hz, 1H, 3′) 1‘2, 7.12-7.22 (m, 2H, 1 & 3), 7.34-7.39 (m, 1H, 2′),
7.45-7.48 (m, 1 H, 2), 7.49, 7.56 (s, 2H, 15 & 15′), 7.99, 8.02 (s, 2H, 9 & 9′), 8.89, 9.01 (s, 2H, 13 & 13′), 15.30, 15.33 (s, 2H, COOH’ & COOH”).
13C-NMR (DMSO-Cf6, 75 MHz, ppm)- δ 18.87, 19.03 (2OC, 20’C), 19.11 , 19.24 (21 C, 21 ‘C), 27.94 (7’C), 28.40 (7C), 28.91 , 30.08 (19C, 19’C), 56.80(23C), 60.11 (171C), 63.59 (18C), 66.52 (18’C), 68.53 (17C), 97.86, 98.97 (15, 15′), 107.43, 108.16 (12C, 12’C),
118.77, 119.38 (1OC, 10’C), 119.57 (d, J=17.6 Hz, 41C), 119.61 (d, J=17.9 Hz, 4C),
124.88 (d, J=4.3 Hz, 31C), 125.18 (d, J=4.2 Hz, 3C), 126.59, 126.96 (9C1 9’C), 127.14 (8’C), 127.62 (d, J=15.9 Hz, 61C), 127.73 (8C), 127.99 (d, J=15.2 Hz, 6C), 128.66 (2’C),
128.84 (11C), 128.84 (2C), 130.03 (d, J=3.4 Hz, 1C), 142.14, 142.44 (14C, 14’C), 144.37, 145.56 (13C, 131C), 155.24 (d, J=245.1 Hz, 5’C)1 155.61 (d, J=245.1 Hz, 5C),
160.17 (16’C), 162.04 (16C), 166.00, 166.14 (22C, 22’C), 176.17, 176.22 (11C, 111C).
DIP MS: m/z (%)- 863 [M+H]+, 885 [M+Na]+.
Orphan Drugs: Bayer Receives FDA Approval
The FDA announces November 22 that orphan drug Nexavar (Sorafenib) receives approval for the treatment of patients with late-stage (metastatic) differentiated thyroid cancer. Nexavar is co-marketed by Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals.
FDA Regulatory Actions for Thyroid Cancer Indication
• In December 2011, receives Orphan Drug Designation (ODD)
• In August 2013, receives Priority Review for supplemental New Drug Application (sNDA)
• In November 2013, receives approval.
The FDA completes its review of Nexavar’s new indication under the agency’s Priority Review Program. A Priority Review designation means that the FDA will take action on a drug application within 6 months, as opposed to 10 months under standard review. If the drug in question is approved, then it will bring “significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.” The FDA decides on the Priority Review designation…
View original post 220 more words
EYLEA® (aflibercept) Injection Approved For The Treatment of Macular Edema Following Central Retinal Vein Occlusion In Japan
TARRYTOWN, N.Y., Nov. 22, 2013 /PRNewswire/ — Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that EYLEA® (aflibercept) Injection has received approval for the treatment of Macular Edema Following Central Retinal Vein Occlusion (CRVO) from the Japanese Ministry of Health, Labour and Welfare.http://www.pharmalive.com/japan-approves-eylea
In November 2011 the United States Food and Drug Administration approved aflibercept for the treatment of wet macular degeneration.
On August 3, 2012 the United States Food and Drug Administration approved Zaltrap (ziv-aflibercept) for use in combination with 5-fluorouracil, leucovorin and irinotecan to treat adults with metastatic colorectal cancer that is resistant to or has progressed following an oxaliplatin‑containing regimen.
In November 2012 the European Medicines Agency (EMA) approved aflibercept for the treatment of wet macular degeneration.
On February 1, 2013 the European Commission granted a marketing authorisation valid throughout the European Union for treatment of adults with metastatic colorectal cancer for whom treatment based on oxaliplatin has not worked or the cancer got worse.
Tecfidera wins “new active substance” designation in Europe
November 22,2013 | By Márcio Barra
Biogen Idec’s multiple sclerosis drug Tecfidera (dymethil Fumarate ) won today designation as a “new active substance” in Europe by the European Medicines Agency, giving it added protection against generic copies and paving the way its approval in European soil.
The designation, issued by the Committee for Medicinal Products for Human Use and posted today on the EMA’s website, gives an additional 10 years of patent protection for Tecfidera, The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) posted this decision on its website today, updating a previous opinion.
View original post 221 more words
Zucapsaicin (Zuacta)
Zucapsaicin (Zuacta), cas 25775-90-0
Chemical name: (Z)-8-methyl-N-vanillyl-6-nonenamide
Molecular formula: C18H27NO3
Molecular mass: 305.41
E merck
Civanex (zucapsaicin) cream is a TRPV-1 modulator in development for the treatment of signs and symptoms of osteoarthritis of the knee.
Zucapsaicin, the cis-isomer of the natural product capsaicin, is a
topical analgesic that was initially developed by Winston Pharmaceuticals
and approved in Canada in July 2010 for the treatment of
severe pain in adults with osteoarthritis of the knee.
Bronson, J.; Dhar, M.; Ewing, W.; Lonberg, N. In Annual Reports in MedicinalChemistry; John, E. M., Ed.; Academic Press, 2011; Vol. 46, p 433.
The advantagesof zucapsaicin compared with naturally-occurring capsaicin, are reported to be a lesser degree of local irritation (stinging, burning,
erythema) in patients and a greater degree of efficacy in preclinical
animal models of pain.
Bernstein, J. E. U.S. 5063060, 1991.
Bernstein, J. E. U.S. 20050084520 A1, 2005.
The analgesic action of both
zucapsaicin and capsaicin is mediated through the transient receptor
potential vanilloid type 1 (TRPV1) channel, a ligand-gated ion
channel expressed in the spinal cord, brain, and localized on neurons
in sensory projections to the skin, muscles, joints, and
gut.
Westaway, S. M. J. Med. Chem. 2007, 50, 2589.
The scale preparation of zucapsaicin likely parallels the original
approach described by Gannett and co-workers involving the
coupling of vanillylamine with (Z)-8-methylnon-6-enoyl chloride.
Gannett, P. M.; Nagel, D. L.; Reilly, P. J.; Lawson, T.; Sharpe, J.; Toth, B. J. Org.Chem. 1988, 53, 1064.
Orito and co-workers elaborated this original approach in
an effort to prepare both capsaicin and zucapsaicin on gram-scale,
Kaga, H.; Miura, M.; Orito, K. J. Org. Chem. 1989, 54, 3477.
Zucapsaicin (Civanex) is a medication used to treat osteoarthritis of the knee and otherneuropathic pain. It is applied three times daily for a maximum of three months. It reduces pain, and improves articular functions. It is the cis-isomer of capsaicin. Civamide, manufactured by Winston Pharmaceuticals, is produced in formulations for oral, nasal, and topical use (patch and cream).[1]
Zucapsaicin has been tested for treatment of a variety of conditions associated with ongoing nerve pain. This includes herpes simplex infections; cluster headaches andmigraine; and knee osteoarthritis.[2]
- Winston Pharmaceuticals websitehttp://www.winstonlabs.com/productdevelopment/civamide.asp
- Zucapsaicin information from the National Library of Medicinehttp://druginfo.nlm.nih.gov/drugportal
- http://products.sanofi.ca/en/zuacta.pdf
CHINESE MEDICINE-Xuezhikang , A blood lipid regulator
Xuezhikang
Xuezhikang, the extract of red yeast rice, has been widely used as a Chinese traditional medicine for the therapy of patients with cardiovascular diseases. It contains natural Lovastatin and its homologues, as well as unsaturated fatty acids, flavonoids, plant sterols and other biologically active substances
The product is a world-recognized blood lipid regulator, which is made by extracting from “specially-made red yeast rice”. It combines modern high-tech biotechnology with traditional Chinese medicine, which can safely and effectively regulate blood lipids in a comprehensive way with proven curative effects and reliable safety.
Pharmacological Effects: the product can reduce blood cholesterol, triglycerides, low density lipoprotein cholesterol, improve high density lipoprotein cholesterol, inhibit atherosclerotic plaque formation, and protect vascular endothelial cells; and inhibit lipid deposition in the liver. The large-scale evidence-based research has proven that long-term use of XUEZHIKANG can greatly reduce the risk of CHD occurrence and decrease the mortality. XUEZHIKANG is the only Chinese medicine with blood lipids regulating function which is listed into the National Basic Medicine List.
Beijing Peking University WBL Biotech (WPU) has developed and launched Xuezhikang, a capsule formulation of Monascus purpureus-fermented rice, for the oral treatment of hyperlipidemia and cardiovascular disease
CLINICAL TRIAL, NCT01327014 PHASE 2
The data had shown that Xuezhikang significantly reduced the level of low density lipoprotein cholesterin (LDL-C) in patients in a similar manner to statins and increased the level of the beneficial high density lipoprotein cholesterin (HDL-C). It had a good safety profile with no significant liver enzyme abnormal events observed. Besides regulation of dyslipidemia, the drug also signifcantly reduced cardiovascular events and general mortality rate of patients
NCT01686451 PHASE 4
Both XueZhiKang and Statins are cholesterol-lowering medications that are often prescribed for individuals with high cholesterol and who are at risk for cardiovascular disease (CVD). Several studies, including one randomized, double-blind, placebo-controlled clinical trial, have suggested that the use of statins is more frequently associated with fatigue. And XueZhiKang may be not. The purpose of this study is to compare the effect of these two medications on fatigue in persons who are at moderate to low CVD risk based on the risk estimation system in ESC(European Society of Cardiology)/ESA(European Atherosclerosis Society) guidelines (2011) for the management of dyslipidemias.
Those of you with high cholesterol will be happy to learn that there are some legitimate options to your statin pills. Many people cannot tolerate the extremely popular statin pills, especially from side effects of muscle aches. But there’s now some very strong evidence that herbal medicines, including red yeast rice, can be at least as effective as a statin, and without the side effects. Too good to be true? Maybe not…
Red yeast rice is a bright reddish purple fermented rice, which acquires its colour from being cultivated with the mold Monascus purpureus. Red yeast rice is known as Zhi Tai when in powdered form but is called Xue Zhi Kang in alcohol extract form. This has been used in China for many centuries for many reasons, but researchers have been very interested in its effectiveness in lowering cholesterol and preventing heart disease (similar benefits from statins). It seems that the main active ingredient is indeed the natural form of a common statin, lovastatin — but researchers feel that other ingredients inside may add more protective effects. There is an official patented Chinese TCM formulation, called Xue Zhi Kang (xue2 zhi1 kang2 jiao nang 血脂康 胶囊), which has the equivalent of 10mg of lovastatin. The ScienceDaily website has a nice 2008 review of a well-designed study, printed in American Journal of Cardiology, which followed 5,000 persons after their first heart attack, and divided them into two groups taking either xuezhikang or placebo. After 5 years:
Frequencies of the primary end point were 10.4% in the placebo group and 5.7% in the XZK-treated group, with absolute and relative decreases of 4.7% and 45%, respectively. Treatment with XZK also significantly decreased CV and total mortality by 30% and 33%, the need for coronary revascularization by 1/3, and lowered total and low-density lipoprotein cholesterol and triglycerides, but raised high-density lipoprotein cholesterol levels. In conclusion, long-term therapy with XZK significantly decreased the recurrence of coronary events and the occurrence of new CV events and deaths, improved lipoprotein regulation, and was safe and well tolerated.
This is impressive data, and the study design is very well done, which means the evidence is quite strong. One co-author, Dr Capuzzi, has a nice summary:
“It’s very exciting because this is a natural product and had very few adverse side effects including no abnormal blood changes,” said Capuzzi. “People in the Far East have been taking Chinese red yeast rice as food for thousands of years, but no one has ever studied it clinically in a double-blind manner with a purified product against a placebo group until now and we are pleased with the results. However, people in the United States should know that the commercially available over-the-counter supplement found in your average health food store is not what was studied here. Those over-the-counter supplements are not regulated, so exact amounts of active ingredient are unknown and their efficacy has not been studied yet.”
- XueZhiKang
In another randomized trial study, printed last year in the Annals of Internal Medicine, patients who had previously failed treatment of statins due to side effects were given 1800mg of red yeast rice twice a day versus placebo. The red yeast rice group had a significant improvement in cholesterol numbers — with no major reports of severe muscle aches they previously had on the statins.
There are other studies that also show similar benefits. In fact, the evidence is so strong that it is classified as Grade A evidence: “Strong scientific evidence for use”. This is the highest grade that any therapy can get. There are a number of good reviews of red yeast rice in Western literature, including from Medscape; the Mayo Clinic; WebMD; MedlinePlus; and NCCAM. There’s also more informal information from the TCM blog Qi Spot. You can find more scholarly information in the 2008 review from Chinese Medical Journal.
http://www.hindawi.com/journals/ecam/2012/636547/
(U.S. patent #6,046,022), ethanol extract of red yeast rice, with a total monacolins content of approx. 0.8%.
1 Heber D et al. Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement. American Journal of Clinical Nutrition 1999;69(2): 231-236
2) SoRelle R. Appeals court says Food and Drug Administration can regulate cholestin. Circulation 200;102 (7): E9012?E9013.
3) Li, C et al. Monascus purpureus-fermented rice (red yeast rice): a natural food product that lowers blood cholesterol in animal models of hypercholesterolemia. Nutrition Research 1998;18 (1): 71-81
4) Becker DJ et al. Red yeast rice for dyslipidemia in statin-intolerant patients: a randomized trial.Ann Intern Med. 2009 Jun 16;150(12):830-9, W147-9
5) Lu Z et al.Effect of Xuezhikang, an extract from red yeast Chinese rice, on coronary events in a Chinese population with previous myocardial infarction. Am J Cardiol. 2008 Jun 15;101(12):1689-93.
Hypochol is the same product. Xuezhikang is the brand name marketed in China. Hypochol, is manufactured by a Singapore comapany who have a joint venture agreement with Peking University who perfected the processing and quality control of the Red Yeast Rice Extract Product. You can order directly from: http://www.hypocol.com/wbm.html
or thru their New Zealand distributor (very good service) at: http://www.hypocol.co.nz/
Dried grain red yeast rice
Red yeast rice (simplified Chinese: 红曲米; traditional Chinese: 紅麴米); pinyin: hóng qū mǐ; literally “red yeast rice”), red rice koji (べにこうじ, lit. ‘red koji‘) or akakoji (あかこぎ, also meaning ‘red koji‘), red fermented rice, red kojic rice, red koji rice, anka, or ang-kak, is a bright reddish purple fermented rice, which acquires its colour from being cultivated with the mold Monascus purpureus.
Red yeast rice is what is referred to, in Japanese, as a koji, meaning ‘grain or bean overgrown with a mold culture’, a food preparation tradition going back to ca. 300 BC.[1] In both the scientific and popular literature in English that draws principally on Japanese, it is most often known as “red rice koji“. English works favoring Chinese sources may prefer the translation “red yeast rice”.
In addition to its culinary use, red yeast rice is also used in Chinese herbology and traditional Chinese medicine. Its use has been documented as far back as the Tang Dynasty in China in 800 AD. It is taken internally to invigorate the body, aid in digestion, and revitalize the blood. A more complete description is in the traditional Chinese pharmacopoeia, Ben Cao Gang Mu-Dan Shi Bu Yi, from the Ming Dynasty (1378–1644).
What other names is Red Yeast known by?
Arroz de Levadura Roja, Cholestin, Hong Qu, Koji Rouge, Levure de Riz Rouge, Monascus, Monascus purpureus, Monascus Purpureus Went, Red Rice, Red Rice Yeast, Red Yeast Rice, Red Yeast Rice Extract, Riz Rouge, Xue Zhi Kang, XueZhiKang, XZK, Zhibituo, Zhi Tai.
What is Red Yeast?
Red yeast is the product of rice fermented with Monascus purpureus yeast. Red yeast supplements are different from red yeast rice sold in Chinese grocery stores. People use red yeast as medicine.
Possibly Effective for…
- High cholesterol.
- High cholesterol and triglyceride levels caused by human immunodeficiency virus (HIV) disease (AIDS).
Insufficient Evidence to Rate Effectiveness for…
- Indigestion, diarrhea, improving blood circulation, spleen and stomach problems, and other conditions.
In the late 1970s, researchers in the United States and Japan were isolating lovastatin from Aspergillus and monacolins fromMonascus, respectively, the latter being the same fungus used to make red yeast rice but cultured under carefully controlled conditions. Chemical analysis soon showed that lovastatin and monacolin K are identical. The article “The origin of statins” summarizes how the two isolations, documentations and patent applications were just months apart.[5] Lovastatin became the patented, prescription drug Mevacor for Merck & Co. Red yeast rice went on to become a contentious non-prescription dietary supplement in the United States and other countries.
Lovastatin and other prescription “statin” drugs inhibit cholesterol synthesis by blocking action of the enzyme HMG-CoA reductase. As a consequence, circulating total cholesterol and LDL-cholesterol are lowered. In a meta-analysis of 91 randomized clinical trial of ≥12 weeks duration, totaling 68,485 participants, LDL-cholesterol was lowered by 24-49% depending on the statin. Different strains ofMonascus fungus will produce different amounts of monacolins. The ‘Went’ strain of Monascus purpureus (purpureus = dark red in Latin), when properly fermented and processed, will yield a dried red yeast rice powder that is approximately 0.4% monacolins, of which roughly half will be monacolin K (identical to lovastatin). Monacolin content of a red yeast rice product is described in a 2008 clinical trial report.
- Website about medicinal use of Monascus purpureus
- Medicinal use of Red yeast rice
- Fermentiertes Rotes Reismehl (in German)
DR ANTHONY MELVIN CRASTO
ORGANIC SPECTROSCOPY
New Drug Approvals 