Gilead Submits New Drug Application to U.S. Food and Drug Administration for Fixed-Dose Combination of Sofosbuvir/Velpatasvir for Treatment of All Six Genotypes of Hepatitis C

FOSTER CITY, Calif.–(BUSINESS WIRE)–Gilead Sciences, Inc. (Nasdaq:GILD) today announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for an investigational, once-daily fixed-dose combination of the nucleotide analog polymerase inhibitor sofosbuvir (SOF), approved as Sovaldi® in December 2013, and velpatasvir (VEL), an investigational pan-genotypic NS5A inhibitor, for the treatment of chronic genotype 1-6 hepatitis C virus (HCV) infection. The NDA is supported by clinical studies exploring the use of 12 weeks of SOF/VEL for patients with genotype 1-6 HCV infection, including patients with compensated cirrhosis and 12 weeks of SOF/VEL with ribavirin for patients with decompensated cirrhosis.

“As the first fixed-dose combination of two pan-genotypic, direct-acting antivirals, SOF/VEL represents an important step forward in the treatment of patients with hepatitis C,” said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer at Gilead. “Genotype 1 is the most prevalent form of HCV in the United States, but worldwide, more than half of people living with HCV are infected with other genotypes. SOF/VEL complements our current HCV portfolio of Sovaldi and Harvoni, offering high cure rates and the potential to simplify treatment and eliminate the need for HCV genotype testing.”

The FDA has assigned SOF/VEL a Breakthrough Therapy designation, which is granted to investigational medicines that may offer major advances in treatment over existing options. The NDA for SOF/VEL is supported by data from four Phase 3 ASTRAL trials, which evaluated the fixed-dose combination in hepatitis C genotypes 1-6. Of the 1,035 patients treated with SOF/VEL for 12 weeks in the ASTRAL-1, ASTRAL-2 and ASTRAL-3 studies, 1,015 (98 percent) achieved the primary efficacy endpoint of SVR12. The ASTRAL-4 study randomized 267 patients with decompensated cirrhosis (Child-Pugh class B) to receive 12 weeks of SOF/VEL with or without ribavirin (RBV), or 24 weeks of SOF/VEL. Those who received SOF/VEL plus RBV for 12 weeks achieved an SVR12 rate of 94 percent,while those who received SOF/VEL for 12 weeks and 24 weeks achieved SVR12 rates of 83 percent and 86 percent, respectively.

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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

Gilead Expands Hepatitis C Generic Licensing Agreements to Include Investigational Pan-Genotypic Agent

–Sofosbuvir/GS-5816 Single Tablet Regimen May Provide Important New Option for Patients in Developing Countries –

FOSTER CITY, Calif.--(BUSINESS WIRE)--Jan. 26, 2015-- Gilead Sciences, Inc. (Nasdaq:GILD) today announced that the company 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. The expanded agreements will allow Gilead’s India-based partners to manufacture GS-5816 and the single tablet regimen of sofosbuvir/GS-5816, once approved, for distribution in 91 developing countries, which together account for 54 percent of the total worldwide population of individuals infected with the hepatitis C virus (HCV).

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.

“Today’s announcement marks an important milestone in Gilead’s effort to make effective hepatitis C treatment accessible to as many patients, in as many places, as quickly as possible,” said Gregg H. Alton, Executive Vice President, Corporate and Medical Affairs, Gilead Sciences. “Developing countries are home to a diverse mix of hepatitis C genotypes, and the development of a medicine that has the potential to cure any patient, regardless of genotype, could help accelerate access to treatment.”

Professor Abhijit Chowdhury, Head of Hepatology, Institute of Post Graduate Medical Education and Research, Kolkata, commented: “Pan-genotypic hepatitis C treatments have the potential to radically change the treatment landscape in developing countries, removing the need for patients to undergo burdensome laboratory tests. Even if testing facilities are available, their cost is a barrier to treatment access, so a regimen that can be used for any genotype is going to be a real attribute in tackling this disease on a global level.”

The amended agreements expand on Gilead’s existing generic licensing partnerships for hepatitis C, announced in September 2014, under which partners may produce sofosbuvir and the single tablet regimen of ledipasvir/sofosbuvir. Eight Indian-based generic manufacturers now hold licenses to manufacture Gilead’s HCV medicines – Biocon Ltd., Cadila Healthcare Ltd., Cipla Ltd., Hetero Labs Ltd., Mylan Laboratories Ltd., Ranbaxy Laboratories Ltd., Sequent Scientific Ltd. and Strides Arcolab Ltd.

Sofosbuvir recently received regulatory approval in India (January 2015), and regulatory submissions have been completed in additional countries, including Pakistan, Thailand, Brazil, Uganda, South Africa and Nigeria.

About GS-5816
The single tablet regimen of sofosbuvir/GS-5816 is an investigational agent and its safety and efficacy have not been established. Phase 3 studies evaluating the combination of GS-5816 and sofosbuvir are currently underway, with data anticipated in the second half of 2015.

Gilead’s Approach to Treatment Access in Developing Countries
Gilead makes it a priority to increase access to its medicines for people who can benefit from them, regardless of where they live or their economic means. In developing countries, Gilead’s treatment access strategies include tiered pricing, voluntary generic licensing (often in advance of U.S./EU regulatory approval), negotiation with national governments, regional business partnerships, product registration, medical education and partnerships with non-profit organizations. This approach has been successfully applied to Gilead’s humanitarian program in HIV over the past 10 years, where seven million patients are now receiving Gilead-based HIV medicines in developing countries.

For more information on Gilead Sciences, please visit the company’s website at www.Gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

- See more at: http://gilead.com/news/press-releases/2015/1/gilead-expands-hepatitis-c-generic-licensing-agreements-to-include-investigational-pangenotypic-agent#sthash.XNY7QWgP.dpuf