UPDATE 2-Merck says hepatitis C treatment to lose "breakthrough" status

Feb 4 (Reuters) - Merck & Co on Wednesday said the U.S. Food and Drug Administration intends to rescind its "breakthrough therapy" designation for the company's experimental combination treatment for hepatitis C because of other recently approved treatments.

Merck, in its fourth-quarter earnings report, said it plans to discuss the matter with the FDA, and still expects to seek U.S. approval for the treatment in the first half of 2015. It consists of a protease inhibitor called MK-5172 and a so-called NS5A inhibitor called MK-8742 that together had received the "breakthrough therapy" designation from the FDA.

The setback for Merck's treatment follows recent approvals of costly oral treatments for the liver disease from Gilead Sciences Inc and AbbVie that have wiped out all signs of the virus in more than 90 percent of patients after eight or 12 weeks.

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HCV Drugs: Triple Drug Regimens, Exclusivity Deals, Merck & Gilead Updates —Alan Franciscus, Editor-in-Chief

At last year’s CROI conference, I wrote about a 6-week study of sofosbuvir, ledipasvir, and GS-9451.  This combination was tested against sofosbuvir/ledipasvir alone for 12 weeks and sofosbuvir/ledipasvir plus GS-9669 for 6 weeks.  The drugs were combined into one-pill, taken once-daily.  There were 20 patients in each arm.

The bottom line is that all 20 patients (100%) achieved a cure in the triple combination of sofosbuvir/ledipasvir and GS-9669 with 6 weeks of treatment.  The most common side effects were headache, fatigue and diarrhea. 

Comments:  This study is a small study and there is currently no information that it has yet entered into phase 3 studies.  But given the high cure rates and low side effects hopefully it will be entered into clinical trials with this combination or perhaps Gilead is researching another inhibitor to include. 

Study: Virological response after 6 week triple-drug regimens for hepatitis C: a proof-of-concept phase 2A cohort study. Authors: A Kohli et al.

Exclusivity Deals
Ever since AbbVie’s VIEKIRA PAK’s approval there have been intense negotiations between insurance companies/pharmacies and AbbVie and Gilead to determine who will be the exclusive distributors of the pharmaceutical HCV medications. These deals will help to drive down the costs of the drugs, and this will hopefully translate into more patients having access to HCV medications.  The real downside is that the decision as to which medication a patient should be prescribed is now being made by someone other than a patient and medical provider. This is very bad news for patients (see "Predictors" article).  The information below is from our blog as of the date that we have put together our newsletter.  If you have been denied treatment in the past, you may want to check the list below (or our Blog) to find out if you would now qualify for insurance coverage.  The agreements are on-going so keep checking back. 

• AbbVie: Express Scripts, AIDS Drug Assistance Programs (ADAPs)
• Gilead: Aetna, Humana, Anthem, CVS
• Both—AbbVie/Gilead:  Prime Therapeutics

Merck
In January, Merck announced that it has been prioritizing portions of its drug development operations including hepatitis C.  In this respect, the development of a two-drug single pill (grazoprevir/elbasvir) will be accelerated.  Merck hopes to apply for marketing approval in the first half of 2015.  The combination is currently in phase 3 studies.  Phase 2 studies of the two drug combination with and without ribavirin in multiple arm studies of monoinfected and HIV/HCV coinfected patient populations with and without cirrhosis resulted in cure rates from 90 to 100%.  The most common side effects were fatigue, headache and general weakness. 

Gilead
Gilead has announced that it has expanded its hepatitis C generic licensing agreements to include the investigational NS5A inhibitor GS-5816, which is being evaluated in Phase 3 clinical studies as part of a single tablet regimen that combines the compound and sofosbuvir for the treatment of all six genotypes of hepatitis C. If approved by regulatory authorities, the sofosbuvir/GS-5816 regimen would become the first pan-genotypic, all-oral single tablet regimen for HCV. A pan-genotypic therapeutic option is particularly important for developing countries, where genotype testing is often unreliable or not readily available.

http://hcvadvocate.org/news/newsLetter/2015/advocate0215.html#2

Merck to Seek Approval of New Hepatitis C Drug by Midyear

If all goes as planned, Merck will soon take a major step forward in the hot pursuit among pharmaceutical companies to produce a newer, better, faster-working drug to treat the millions of people who have chronic hepatitis C infection.

By midyear the company expects to submit a New Drug Application to the Food and Drug Administration for approval of grazoprevir/elbasvir, a combination regimen investigational drug designed to be taken once daily as treatment of chronic hepatitis C virus infection. Grazoprevir is an NS3/4A second-generation protease inhibitor and elbasvir is an NS5A inhibitor.

 - See more at: http://www.hcplive.com/articles/Merck-to-Seek-Approval-of-New-Hepatitis-C-Drug-by-Midyear#sthash.maxgPR9Q.dpuf

Merck Accelerates Lung Cancer, Hepatitis C Drugs

Merck plans to file an application with the U.S. Food and Drug Administration in the first half of 2015 for the grazoprevir and elbasvir once-daily combination hepatitis C medicine, the company said in a statement today, joining AbbVie Inc. (ABBV:US) and Gilead Sciences Inc. (GILD:US) in creating drug cocktails that can treat the disease in many patients. Merck also plans to apply for permission to expand use of the melanoma treatment Keytruda into non-small cell lung cancer patients.

Merck replaced its head of research in 2013 with Roger Perlmutter and focused development efforts on oncology, hepatitis C, cardiometabolic disease, antimicrobial resistance and Alzheimer’s disease. The Kenilworth, New Jersey-based company has needed new approvals to make up for a decline in sales from the asthma drug Singulair, which lost patent protection in the U.S. in 2012 and in Europe in 2013. Singulair sales fell from $5.5 billion in 2011 to $1.2 billion in 2013.

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