Sofosbuvir (formerly referred to as both GS-7977 and PSI-7977) is a nucleotide analog polymerase inhibitor

Dec 15
GS-7977 HCV Transplant Studies 

Dec 13 2012
Hepatitis C - Initiation of cohort 2 in the interferon-free phase II trial combining simeprevir (TMC435) with sofosbuvir (GS7977) based on a safety and efficacy

Dec 8 2012
Gilead Sciences Leads The Race In Developing A Hepatitis C  Pill

Sofosbuvir (GS-7977) plus peginterferon/ribavirin in treatment-naïve patients with HCV genotype 1: a randomized, 28-day, dose-ranging trial

Dec 3 2012
GILEAD ANNOUNCES SUSTAINED VIROLOGIC RESPONSE RATE OF 78% FROM
PHASE 3 STUDY OF SOFOSBUVIR FOR GENOTYPE 2/3 HEPATITIS C INFECTED
PATIENTS   

November 2012

AASLD Updates
Daclatasvir and Sofosbuvir: Promising HCV Combo May Not See Light of Day

Slides Available @ NATAP- High Rate of Sustained Virologic Response With the All-Oral
Combination of Daclatasvir (NS5A Inhibitor) Plus Sofosbuvir (Nucleotide NS5B
Inhibitor), With or Without Ribavirin, in Treatment-Naive Patients Chronically
Infected With HCV GT 1, 2, or 3

Investment Commentary - Gilead May Top Rivals With Hepatitis C Therapy Results

AASLD-100 Percent Sustained Virologic Response Rate (SVR4)  Interferon-Free Regimen of Sofosbuvir (GS-7977), GS-5885 and Ribavirin in Treatment-Naïve Geno 1 Hepatitis C Infected Patients

October 2012
New report highlights hepatitis C protease inhibitors, nucleotide agents, Non-nucleoside inhibitors and Cyclophilin inhibitors
A special report provided by EASL of the EASL-AASLD Conference on - Therapy of Hepatitis C: Clinical Application and Drug
Development is now available, the report highlights New hepatitis C drugs which is provided below.
Other topics in the report include;
Therapy of Hepatitis C:Clinical Application and Drug Development
HCV transmission and therapeutic intervention
One year of triple combination therapy New HCV drugs in development
Overcoming resistance and treatment  failure
New ways to search for novel anti-HCV drugs
Download PDF 

New HCV drugs in  development
“We have come a long way with interferon treatment since it was first introduced in 1991 to the use of pegylated interferon as part of triple HCV therapy today. Some are predicting therapy will be interferon-free. But we need all the tools we can get to improve the management of HCV and novel interferons and IFN inducers may have an important role in some patient subgroups,” said Dr. Michael Manns, Medical School of  Hannover, Germany. 

He suggested that interferon-based therapies have several potential advantages compared to direct antiviral agents:  
• No viral resistance
• Comparatively low cost
• Vast clinical experience
• Potential use in other viral infections such as HBV. 

For the future, INF-based therapy may be appropriate for easy to treat patients, but new interferons have to be developed
that are much safer and better tolerated than current options. 

Newer NS3/4A protease inhibitors in combination with peg-IFN and ribavirin achieve high rates of SVR with simpler dosing
schedules and generally better tolerability than older agents, according to Dr. Michael Fried, University of North Carolina, USA. He said that two years of clinical experience with the currently available PIs have shown that ribavirin is required for achieving SVR, rapid virological response is associated with highest SVR and adverse events can generally be managed
but that certain  populations are less responsive. New PIs in development include simeprevir and faldeprevir (phase 3) and asuneprevir and ABT- 450/r (phase 2), mostly with peg-INF + RBV backbone. Trials so far show encouragingly high rates of SVR and generally good tolerability, but we have to wait for more data, he concluded. 

“It’s becoming clear that nucleoside/nucleotide analogues provide a very strong backbone for future HCV therapies,” argued Dr. David Nelson, University of Florida, USA. They work by causing premature chain termination during viral nucleic acid synthesis. The active binding site in the target – NS5B RNA-dependent RNA polymerase – is highly conserved across HCV
genotypes, conferring pangenotypic activity and there is a high barrier to resistance. Three agents are currently in development: sofosbuvir (phase 3),  mericitabine (phase 2) and ALS-2200 (phase 2), while some others have been put
on hold due to toxicity. 

“Sofosbuvir (previously GS-7977) will be the most important compound during the next 2-4 years,” predicted Professor
Wedemeyer. He noted that sofosbuvir therapy was successful in various IFN-free regimens and may also help to shorten IFNa-based therapies. “However, we have learned over the last few months that there will be no ‘one-size-fits-all’regimen with sofosbuvir.” 

Non-nucleoside inhibitors of HCV RNA polymerase have no role in monotherapy and limited role in triple therapy, but they may be useful in quadruple therapy, suggested Dr. Paul Pockros, La Jolla, USA.  Reviewing the available data, he noted that these agents have low to moderate potency, a low barrier to resistance and are unlikely to have crossgenotype activity. “Of the 13 non-nucleoside inhibitors in development in 2008, a lot have given disappointing results, with only six remaining,” he said.
Of these, Vx-222 is the most potent, achieving a 3.4 log10 reduction in viral load (at a dose of 400mg bid) and is currently in phase 2. However, some compounds may still be used in IFN-free treatment regimens if combined with other highly potent DAAs. 

Therapeutic vaccines represent a scientifically valid approach to treating HCV but there is a long way to go to optimise
vaccine response, suggested Professor Heiner Wedemeyer. He questioned whether vaccines for HCV are needed at all, with all the new drugs currently in development, but suggested several reasons why they may be useful.
“First, HCV is not HIV,” he pointed out. “Immune control of HCV is possible, in contrast to HIV infection.” Clinical observations show – quite remarkably – that 10-50% of cases of acute hepatitis C are cleared without treating, suggesting a major role for the immune system.
 
Combinations including NS5A inhibitors appear likely to address many of the current unmet medical needs in HCV, especially for patients who remain difficult to treat with currently available therapies, including those with cirrhosis and patients undergoing liver transplant, according to Dr. Stanislas Pol, Hopital Cochin, France. Reviewing the data with daclatasovir, the first agent in the class, he said it is very potent, has broad genotypic coverage and has a pharmacokinetic profile supportive of once daily dosing, making it easy to take. A recent study with quadruple therapy including daclatasovir, asapravir and peg-interferon/ ribavirin has shown ‘fantastic results,’ he said, with SVR4 of 90-100% in a difficult to treat group of  genotype 1 null responders. Moreover, NS5A inhibitors are part of many IFN-free treatment regimens.

Cyclophilin inhibitors offer the benefits of a high barrier to resistance and no cross-resistance with protease or polymerase
inhibitors, Professor Robert Flisiak, Medical University of Bialystok, Poland, told the meeting. They act on NS5A, NS5B and NS2 HCV viral proteins, as well as preventing HCV-mediated mitochondrial and endogenous interferon production. 

Alisporivir – the most advanced agent in the class – has shown effects in treatment naïve, previous non-responders and in
HIV/HCV coinfected patients. It has demonstrated antiviral efficacy against the four most prevalent genotypes (1,2,3 and 4). It is effective in interferon-free regimens, as well as providing additional antiviral effects in combination with peg-interferon plus ribavirin, and is well tolerated.
However, it is currently on hold due to toxicity in combination with PEG-IFNa. Future trials may therefore focus on IFN-free regimens including alisporivir. 

Entry inhibitors, which block the entry of HCV  into cells, are at an early stage of development but proof of the concept has
been demonstrated in cell culture and in vivo models, reported Professor Thomas Baumert, University of Strasbourg, France. They are pangenotypic, prevent infection with escape variants and provide a complementary mechanism of action
of direct antiviral agents, demonstrating marked synergy. “They offer a very attractive antiviral strategy for the prevention of liver graft infection in patients who have undergone transplantation, as well as for difficult to treat patients and those with multiresistance,” he suggested.
Download PDF

Sept 2012

Sept 14-
GS7977- Gilead Sciences biotech's hepatitis C program
Sept 10
GS-7977 HCV Nucleotide in Phase 3 Now
6 New HCV Drugs in Phase 3 Now
FDA and 3 European regulatory agencies, and agreement has been achieved on a comprehensive Phase III development plan for GS-7977 and on a Phase III plan for GS-7977 in combination with the NS5A inhibitor, GS-5885.......we anticipate being able to file for regulatory approvals for GS-7977 by the middle of next  year......

Aug 2012
Gilead: A Stock For The Future

Weekly HCV Rewind- A Look At Gileads Pan-Genotypic Drug GS-7977

July 2012

Gilead Begins Single Pill Hepatitis C Study For 2014 Approval

By Michelle Fay Cortez and Ryan Flinn on July 27, 2012
 
Gilead Sciences Inc. (GILD) said it plans to start a combination study of two drugs in a single pill to treat hepatitis C
by the end of the year, putting it on track to request U.S. regulatory approval for the medicine in 2014. 

Gilead, which spent $10.8 billion to acquire one of the medicines, GS-7977, plans to combine it with another, GS-5855, in a trial of 800 patients starting in the fourth-quarter, said Norbert Bischofberger, chief medical officer of the Foster City, California-based company, in a conference call yesterday. If the combination is effective, the company could apply for  regulatory approval in the middle of 2014, Bischofberger said. 

Gilead is among several drugmakers racing to develop new hepatitis C treatments that act more quickly with fewer side effects than the current standard of care. The goal is to provide doctors and patients with simpler, more effective treatments, Bischofberger said. 

The company aims for a therapy that “will clearly be a one pill, once daily, maybe a 12 week course,” for patients with all different types of hepatitis C, Bischofberger said. “That’s our goal. We are very close.”
Continue reading @ Bloomberg


June 2012

Bristol Hep C Trial Change Has Big Implications
By Ed Silverman //   June 20th, 2012 //
Is a promising new class of drugs for treating hepatitis C going to be limited because patients with the most common genotype of the virus are likely to develop resistance to the medications? This is the possibility raised by a Wall Street analyst after learning that Bristol-Myers Squibb last week altered the protocol for a clinical trial for its daclatasvir antiviral, which is
believed to be the most potent in the forthcoming NS5a class of hepatitis c treatments.

According to ClinicalTrials.gov, the drugmaker changed the protocol to its COMMAND-3 trial, which compares its drug in combination with interferon and ribavirin to Incivek, a protease inhibitor sold by Vertex Pharmaceuticals, along with interferon and ribavarin. What was the change? Bristol-Myers restricted future enrollment to patients who have only genotype 1b HCV, rather than all genotype 1 patients (see this and this).

“This effectively eliminates from the trial the most common HCV genotype in the US – 75 percent of HCV is genotype 1 in the US, 80 percent of genotype 1 is genotype 1a,” Sanford Bernstein analyst Tim Anderson writes in an investor note.
“This change, some three months after the study started enrollment, suggests that some form of virologic failure has emerged in the patients with these genotypes… The NS5a class, as a whole, might be limited by the propensity to rapidly develop virological resistance, and by significant differences in potency from one viral genotype to another.” 

He adds that the change in the protocol has “major strategic and tactical implications” for the hot and fast-growing hepatitis C market. How so? Several drugmakers are developing NS5a treatments and the possibility that these drugs generate resistance to the virus may prompt changes in how different types of medications are combined and, consequently, alter various corporate strategies for drug development, alliances and dealmaking.

Take Gilead Sciences. The drugmaker is developing an NS5a, which has the code name of GS5885, as well as another that is a nucleotide inhibitor, or nuke,which Gilead calls GS7977 and believes could be the cornerstone of the first all-oral regimen for hepatitis C. Gilead, you may recall, acquired GS7977 last fall as part of its $11 billion acquisition of Pharmasset, a bet that has
transformed the investor view of the drugmaker (back story).

Two months ago, results of a study that combined daclatasvir with GS7977 suppressed hepatitis C in most patients four weeks after completing treatment, raising hopes about the prospects for a therapy that does not involve an injectable medication. But further collaboration between the two drugmakers appeared uncertain, because Gilead indicated a preference for developing its own NS5a drug with GS7977 (see this).

However, as Anderson notes, the Gilead NS5a drug is less potent than daclatasvir, which “increases the risk for Gilead of sticking with GS5885. On the Bristol side, their ‘go-it-alone’ strategy may be developing a hole, increasing the urgency of incorporating daclatasvir into an all-oral combination with a potent resistance-fighting nuke such as GS7977. This collaboration
appears to have become more important to both parties,” he writes.

Both drugmakers recently declined comment on this topic, although late last month, Bristol-Myers ceo Lamberto Andreotti renewed a call for Gilead to jointly develop their hepatitis C medications. We asked Bristol-Myers about the change in the trial protocol and will update you with any reply that we receive.

Looking ahead, Anderson sees greater potential for combination therapy that relies on three drugs, instead of two, including GS7977 from Gilead, since the response to NS5a drugs suggests there can be limitations to at least one of the agents that developers would want to use in a one-two punch. And he believes Gilead’s prospects for creating one “super-regimen” for all subtypes with GS7977 and GS5885 alone, or even with ribavirin, have fallen.  

As for other drugmakers, the questions concerning the NS5a drugs may result in slightly extended utility for Incivek as well as Victrelis, another protease inhibitor that is sold by Merck. This also suggests additional jockeying surrounding the NS5a drugs being developed by Achillion Pharmaceuticals and Idenix Pharmaceuticals, since larger drugmakers may decide to adjust their
strategies and portfolios in response to the changing dynamics of this class of treatments.

“All this incremental insight about the limitations of different classes means the portfolios of the committed participants in the field will likely need to be larger than previously anticipated,” Anderson opines. “If, indeed, the field migrates to a three-mechanism standard, then smaller companies with one or more relatively isolated drugs, will be even more compelled to accept offers from buyers, and those buyers are likely to also require even more compounds than they have today, increasing the pressure on them to secure the few remaining independent assets.”
http://www.pharmalot.com/2012/06/bristol-hep-c-trial-change-has-big-implications/

June 7, 2012
Open-Label  Study of GS-7977+ Ribavirin for 12 Weeks in Subjects With Chronic HCV  Infection
This study is not yet open for participant  recruitment.
Verified June 2012 by Gilead Sciences  
First Received on  June 7, 2012.  
Last Updated on June 19,  2012  History of  Changes
GS-7977 in combination with ribavirin
 
Open-Label Study of GS-7977 + Ribavirin Pre-Transplant
An Open-Label Study to Explore the Clinical Efficacy of GS 7977 With  Ribavirin Administered Pre-Transplant in Preventing

Hepatitis C Virus (HCV)  Recurrence Post-Transplant
This study is currently  recruiting participants.
Verified April 2012 by  Gilead Sciences

Purpose
The primary objective is to determine if the administration of a combination of GS 7977 and ribavirin to HCV-infected subjects with hepatocellular carcinoma (HCC) meeting the MILAN criteria prior to undergoing liver transplantation for up to 24 weeks can  prevent post-transplant re-infection as determined by a sustained  post-transplant virological response (HCV RNA < LLoQ) at 12 weeks post-transplant.

Estimated Enrollment: 40
Study Start Date:
March  2012
Estimated Study Completion Date: March 2013 

Estimated
Primary  Completion Date: March 2013 (Final data collection date for primary outcome  measure)

The Buzz
Interim results on Gilead's GS-7977 and Bristol-Myers Squibbs' daclatasvIr resulted in
100% SVR in genotype 1 treatment-naive patients. However the two drug companies
Bristol-Myers  Squibb and Gilead haven't yet agreed to collaborate on  the
all oral promising combination.

Excerpt-The Street
Grading hep C stocks exiting EASL confab

As if that weren't enough excitement, Gilead also
generated some drama at the meeting -- and elicited a "patients-not-profits"
 rebuke from my colleague Adam Feuerstein -- when word got out that the company had refused
 an offer from Bristol-Myers to collaborate on further development of GS-7977 and
daclatasvir. Although Gilead insists it hasn't made a final decision, I'm
guessing management will try to combine GS-7977 with GS-5885, an early-stage
drug candidate in the same NS5A class as daclatasvir. Obviously, Gilead wants to
keep all the profits from a highly potent, all-oral hepatitis C therapy for
itself.  

In GS-7977, Gilead appears to control a strong, future
"backbone" for any next-generation hepatitis C regimen. I have mixed feelings
about Gilead's apparent desire to deny Bristol-Myers access to the drug and
therefore prevent a daclatasvir-GS-7977 regimen from reaching the market.
Patients and their advocates will probably be justifiably upset that such this
apparently highly effective regimen won't be developed further. I understand
that. Interestingly, physicians I spoke with at the meeting didn't care either
way. That surprised me; I would have expected more complaints. 

As an investor, I don't fault Gilead for angling to maximize profits -- I've never
subscribed to the biotechnology industry's cloying "patients first" rhetoric.
However, the move does increase the company's clinical risk in hepatitis C.
 Even though initial GS-5885 data look clean, a problem could still emerge and daclatasvir is far
more established. Essentially, management is betting that the promise (and eventually, the reality) of
 an "all Gilead" HCV regimen outweighs additional R&D expenses and near-term clinical
risks



Interim results presented at the EASL
Daclatasvir and GS-7977 (SVR4) in 100% of Genotype 1 and 91% of Genotype 2 and 3 Treatment-Naïve Patients
 
EASL-All Oral Combo Daclatasvir and GS-7977=100% SVR Geno 1 and 91% SVR Geno 2 and 3 "SVR=4 weeks after-treatment"

Press Release--
April 19, 2012 05:00 AM Eastern Daylight Time 

All-Oral Combination of Investigational Hepatitis C (HCV) Compounds
Daclatasvir and GS-7977 Achieved Sustained Virologic Response (SVR4) in 100% of
Genotype 1 and 91% of Genotype 2 and 3 Treatment-Naïve Patients in Phase II Study

First demonstration of 100% SVR with once-daily,  interferon- and
ribavirin-free regimen in treatment-naïve genotype 1 HCV 
patients 

First report of a study designed to assess  antiviral efficacy of a
NS5A replication complex inhibitor and a NS5B nucleotide  polymerase inhibitor
as potential combination HCV therapy 

All-oral investigational treatment regimen  suppressed viral load
through 4 weeks post-treatment  (SVR4) in genotypes 1, 2 and 3, with or 
without ribavirin 
 
PRINCETON, N.J.--(BUSINESS  WIRE)--Bristol-Myers Squibb Company
(NYSE: BMY) announced today  interim results from a Phase II open-label study of
daclatasvir, Bristol-Myers  Squibb’s NS5A replication complex inhibitor, and
GS-7977, a nucleotide NS5B  polymerase inhibitor, in treatment-naïve patients
with hepatitis C genotypes 1,  2 and 3. In this interim analysis, a combination
of the two oral, once-daily  investigational compounds taken for 24 weeks, with
or without ribavirin,  achieved a rapid and sustained viral response. Overall,
100% of patients with  genotype 1, 2, or 3 HCV achieved viral load below the
lower limit of  quantification at Week 4 on treatment. In the genotype 1 HCV
treatment groups,  100% of patients achieved sustained virologic response
through four weeks  off-treatment (SVR4). In the genotypes 2 and 3 treatment
groups, 91%  (40/44) of patients achieved SVR4.
The data were presented today at  the International Liver Congress (ILC), the
47th annual meeting of the European  Association for the Study of the Liver
(EASL) in Barcelona, Spain.

The most frequent (≥25% overall) adverse events (AE) on treatment, based upon  the most recent 12-week
interim safety analysis, were fatigue, headache and  nausea. Drug-related AEs
were generally mild and did not lead to treatment  discontinuation. Grade 3-4
laboratory abnormalities occurring in patients in the  ribavirin treatment
groups included anemia, elevated glucose, elevated fasting  glucose, lymphopenia
and low serum phosphorus, and the grade 3-4 laboratory  abnormalities reported
in the ribavirin-sparing treatment groups were low  phosphorus and elevated
cholesterol.

“The achievement of high SVR rates with a once-daily, pan-genotypic oral  combination regimen
has emerged as a key goal in HCV  research,” said Mark  Sulkowski, MD, Professor of Medicine,
Medical Director,  Viral Hepatitis Center,  Johns Hopkins University School of Medicine. “The
interim results of this study  indicate that combining the potent antiviral
activity of daclatasvir with a  nucleotide analogue polymerase inhibitor has the
potential to address this goal  for the treatment of HCV genotypes 1, 2 and 3,
and warrants further study to  more fully evaluate this combination.”

Daclatasvir has demonstrated potent antiviral activity against HCV genotypes
  1, 2, 3, and 4 in vitro.

Study Results
In the study, 88 treatment-naïve patients were divided into six treatment  groups. The
proportions of patients achieving viral load below the lower limit  of
quantification (HCV RNA <25 IU/mL) were:
Picture
a- In this  study, SVR4 was defined as viral load below the lower limit of  quantification. All but one
patient who achieved SVR4 also had  undetectable viral load (HCV RNA <10 IU/mL); this patient had undetectable 
viral load when retested eight days later.   
b- One  patient experienced viral relapse and one patient
experienced viral  breakthrough.   
c- Two  patients were lost to follow-up.
 
Safety data from this ongoing study are available through 12 weeks  on-treatment.
The most frequent (≥25% overall) adverse events (AEs) on treatment  were fatigue, headache
 and nausea. AEs were generally mild to moderate intensity  and did not lead to treatment
discontinuation. Grade 3-4 laboratory  abnormalities included anemia, elevated
glucose, elevated fasting glucose,  lymphopenia and low serum phosphorus– all of
which occurred in patients who  received ribavirin. Grade 3-4 laboratory
abnormalities reported in the  ribavirin-sparing treatment groups were low
phosphorus and elevated cholesterol.  Two patients discontinued treatment for
non-drug related AEs and both achieved  SVR4. An additional two patients with
genotype 2 who received daclatasvir,  GS-7977 and ribavirin discontinued the
study for non-AE-related reasons and were  lost to follow-up. No patients
discontinued therapy due to treatment-related  AEs. Of the 88 patients treated,
one patient with genotype 3 HCV who received  GS-7977 and daclatasvir without
ribavirin experienced viral relapse, and one  patient met the protocol
definition of viral breakthrough – HCV RNA below the  lower limit of
quantification on or after Week 8, confirmed by immediate  retesting. This
definition of viral breakthrough is not widely accepted and has  since been
removed from the protocol.

About the Study
This Phase II  study (AI444-040) was designed to evaluate the potential to achieve 
sustained virologic response with an oral,  pan-genotypic, once-daily treatment 
regimen combining daclatasvir (DCV) and Gilead Sciences Inc.’s GS-7977, with or  without ribavirin, in patients
chronically infected with HCV genotypes 1, 2 and  3. In the initial phase of
this study, patients were randomized into six groups,  evaluating three
different dosing schedules in patients with HCV genotype 1  (n=44) and in
patients with HCV genotype 2 or 3 (n=44). 

  • GS-7977 400 mg QD for 7 days then DCV 60 mg QD + 
    GS-7977 400 mg QD for 23 weeks

  • DCV 60 mg QD + GS-7977 400 mg QD for 24 weeks

  • DCV 60 mg QD + GS-7977 400 mg QD + ribavirin for 24 
    weeks
The study was subsequently expanded to include four new
treatment arms that  evaluate HCV genotype 1 patients who have previously failed
telaprevir or  boceprevir treatment, and shorter duration of therapy in
treatment-naïve HCV  genotype 1 patients. These treatment groups are currently
under study.

The primary endpoint of the study is sustained virologic
response 12 weeks  post-treatment (SVR12). An interim analysis for safety
and antiviral  activity was conducted at 12 weeks on-treatment. An additional
interim analysis  for antiviral efficacy was conducted four weeks
post-treatment. Final study  results will be presented at a future medical
meeting.
Continue Reading...

EASL 2012-Potent Viral Suppression With the All-Oral Combination of Daclatasvir
(NS5A Inhibitor) and GS-7977 (Nucleotide NS5B Inhibitor), +/- Ribavirin, in
Treatment-Naive Patients With Chronic HCV GT1, 2, or 3 (100% SVR gt1, 91%
gt2)

Reported by Jules Levin
EASL 2012 Barcelona, Spain April 18-22
Slides Provided By NATAP

Sulkowski M,1 Gardiner D,2 Lawitz E,3 Hinestrosa F,4 Nelson D,5 Thuluvath P,6 Rodriguez-Torres M,7 Lok A,8 Schwartz H,9 Reddy KR,10 Eley T,2 Wind-Rotolo M,11 Huang S-P,11 Gao M,12 McPhee F,12 Hindes R,13
Symonds W,13 Pasquinelli C,2 Grasela D,2 for the AI444040 Study Group 1Johns Hopkins University, Lutherville, MD, USA; 2Bristol-Myers Squibb, Hopewell, NJ,  USA; 3Alamo Medical Research, San Antonio, TX, USA; 4Orlando Immunology Center,
Orlando, FL, USA; 5University of Florida, Gainesville, FL, USA; 6Mercy Medical Center, Baltimore, MD, USA; 7Fundacion de Investigacion, San Juan, Puerto Rico; 8University of Michigan, Ann Arbor, MI, USA; 9Miami Research Associates, South
Miami, FL, USA; 10University of Pennsylvania, Philadelphia, PA, USA; 11Bristol-Myers Squibb, Princeton, NJ, USA; 12Bristol-Myers Squibb, Wallingford, CT, USA; 13Gilead Sciences, Foster City, CA, USA



ELECTRON TRIAL GS-7977/Ribavirin Genotypes 1-3

EASL-Once Daily GS-7977 Plus Ribavirin in HCV Genotypes 1-3: The ELECTRON Trial
Download PDF Here
E. Gane1, C. Stedman2, R. Hyland3, R. Sorensen3, W. Symonds3, R. Hindes3, M. Berrey
1New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, 2Gastroenterology Department, Christchurch Hospital, Christchurch, New Zealand; 3Gilead Sciences, Foster City, CA
Introduction
  • GS-7977 (formerly PSI-7977) is a potent, specifi c nucleotide analog developed for the treatment of patients chronically infected with hepatitis C virus (HCV)
  • Safe and well tolerated in clinical studies
  • Once daily, with or without food
  • Potent antiviral activity
  • High barrier to resistance
─ No virologic breakthrough to date
  • We conducted a Phase 2 trial (ELECTRON) to evaluate the safety and effi cacy of GS-7977 and ribavirin (RBV) with and without pegylated interferon (PEG) in genotype (GT) 1-3 patients with chronic HCV infection
  • Results from the fi rst 5 arms of ELECTRON using interferon-sparing/-free regimens in patients with HCV GT 2/3 and GT 1 prior null responders:1,2,3,4
─ SAFETY
  • GS-7977 400 mg QD + RBV for 12 weeks was well tolerated with no attributable safety signal
─ POTENCY
  • GS-7977 + RBV elicited rapid suppression of HCV RNA → 100% RVR
  • All GT 2/3 treated with GS-7977 + RBV patients achieved SVR24
  • Patients treated with GS-7977 monotherapy achieved 60% SVR24
  • GT 1 prior null responders achieved 11% SVR4 with a 12-week GS-7977+ RBV regimen
  • No virologic breakthrough has been observed during treatment with GS-7977
Objective To evaluate the safety and efficacy of GS-7977 400 mg once daily in combination with RBV with RBV with and without PEG in the following populations:
  • Treatment-naïve GT 2/3 patients treated with GS-7977 + RBV + PEG for 8 weeks
  • Prior null responder GT 1 patients treated for 12 weeks with GS-7977 + RBV
  • Treatment-naïve GT 1 patients treated for 12 weeks with GS-7977 + RBV
  • Previously treated GT 2/3 patients treated for 12 weeks with GS-7977 + RBV
Methods
Figure 1. ELECTRON Study Design
Null responders were defi ned as patients with <2 log10 IU/mL decline from baseline HCV RNA after at least 12 weeks of PEG and RBV
  • Treatment-experienced patients were defi ned as those who had any of the following responses after at least 12 weeks of PEG and RBV: • <2 log10 IU/mL decline from baseline in HCV RNA • ≥2 log10 IU/mL reduction in HCV RNA, but HCV RNA >LOQ at end of treatment • HCV RNA LOQ (relapsers)
Results
Table 1. Baseline Patient & Disease Characteristics
Figure 2. On-treatment Viral Suppression
Table 2. Patients with HCV RNA
*1 subject relapsed at the SVR8 time point after having previously achieved SVR4
Table 3. Safety and Tolerability
*SAEs considered unrelated to GS-7977 †In >1 patient treated with GS-7977; no Grade 3 or 4 AEs occurred in treatment arms lacking PEG
Resistance Data:
  • Population sequencing has been completed in 5 of 8 relapsers from the GT-1 prior null responder arm: no S282T was found
  • Deep sequencing did not identify any S282T-containing mutants
Table 4. Grade 3 or 4 Laboratory Abnormalities in >1 Patient
Conclusions
  • 88% of treatment-naïve GT 1 patients achieved SVR4 following 12 weeks of therapy with GS-7977 + RBV ─ This result suggests that 12 weeks of GS-7977 + RBV can potentially provide higher rates of SVR in treatment-naïve GT 1 patients than those achieved with longer durations of PI + PEG/RBV
  • The combination of GS-7977 + RBV was well tolerated in all genotypes regardless of prior treatment history
  • No virologic breakthrough occurred in any arm, suggesting a high barrier to resistance ─ To date, the S282T mutation has not been seen in any GS-7977/RBV regimen
  • These results where GS-7977 400 mg once daily (QD) is being utilized in a variety of regimens and populations further demonstrate the utility of GS-7977 across a broad spectrum of HCV disease treatment
47th Annual Meeting of the European Association for the Study of the Liver April 18 - 22, 2012 Barcelona, Spain
Gilead Sciences, Inc. 333 Lakeside Drive Foster City, CA 94404 Tel: (650)522-5373
Poster Number 1113
References and Acknowledgements
1. Lawitz E, et al. J Hepatol 2011;54:S543. 2. Gane E, et al. AASLD 2011 3. Gane E, et al. APASL 2012 4. Gane E, et al. CROI 2012
Thanks to all the patients and their families and: • Christian Schwabe, Vithika Suri, ACS • Catherine Stedman, Richard Robson, CCS
© 2012 Gilead Sciences


Disappointment- GS-7977 plus ribavirin genotype 1 null responders

In the phase II Electron trial researchers  reported  in March all but one patient relapsed within days of
stopping  Gilead'sGS-7977 plus ribavirin in a small arm of 10 genotype 1 null  responders.

Medpage reported :

In earlier results  from the phase  II ELECTRON study, patients with genotypes
2 and 3 of the  virus were completely cured after just 12 weeks of therapy with
PSI-7977  combined with  ribavirin, Gane noted.

But researchers were also testing  the combination in 10 patients with
genotype 1 hepatitis C who had  previously not responded to standard therapy with
ribavirin and interferon, and in 25  genotype 1 patients who had not yet been
treated, Gane  said.

The initial responses in both groups were similar to  those seen in genotypes
2  and 3 -- a quick drop to undetectable levels of virus followed by complete 
suppression throughout the 12-week treatment period, Gane said. But
  all but one of the so-called null responders relapsed, with hepatitis C 
levels rising sharply within days of stopping the drug, Gane reported. Data 
on the treatment-naïve patients is not complete yet and will be reported in 
 the next few months, he added.

"It's still a drug we're excited  about, but these data put some limits on its
use," Thomas said.

"The drug was curing [patients with] genotypes 2 and 3 in 12 weeks with just  
ribavirin," he said, but that doesn't appear to be possible in  the hardest-to-treat subgroup.

Read More:Medpage Today

Gilead Sciences - GS-7977 in  combination with PEG-IFN and  ribavirin
In the  ATOMIC study ninety percent of people with
genotype 1 who never treated before  for the first time show a clear sign of
being cured of their  infection using a  12-week treatment regimen containing
Gilead Sciences’ nucleotide analogue  GS-7977 plus pegylated interferon and
ribavirin (peg-IFN/RBV), according  to preliminary data from a
Phase II clinical trial  presented Thursday, April 19, at  the 47th Annual
Meeting of the European  Association for the Study of the Liver  (EASL) in
Barcelona.

The new  results, highlighting 12-week sustained virologic
response (SVR 12) rates  involving one group of patients in the ATOMIC study,
were presented by Kris  Kowdley, MD, of the Virginia Mason Medical Center in
Seattle and his colleagues.  The study, which is ongoing, has enrolled 316
people with genotype 1 HCV  infection to receive either 12 weeks of GS-7977 plus
peg-IFN/RBV, 24 weeks of  GS-7977 plus peg-IFN/RBV or 12 weeks of GS-7977 plus
peg-IFN/RBV plus an  additional 12 weeks of  either GS-7977 alone or GS-7977
plus ribavirin (but not  pegylated interferon). 

An additional 16  patients with genotypes 4 or 6 HCV infection are also enrolled  in ATOMIC
and  will be receiving a 24-week  course of GS-7977 plus peg-IFN/RBV.  SVR 12 data are  only available for the 52
patients in the first group,  treated with GS-7977  plus peg-IFN/RBV for 12
weeks. All of the study volunteers had HCV viral loads  above 50,000; none of
the patients had cirrhosis of the   liver.

According to Kowdley’s EASL report, 51 of the 52 patients  completed 12 weeks of treatment; the remaining
study volunteer was lost to  follow-up during therapy. All 51 patients (100
percent) had an end-of-treatment  response (ETR)—an undetectable HCV viral load
after completing 12 weeks of  therapy.

Data were available for 50 of the 51 study volunteers 12 weeks  after completing therapy; one additional patient
was lost to follow-up during  this period.

Of the 50 evaluable patients, 47 of them—90 percent of the  original 52 study group volunteers—still
had an undetectable HCV viral load 12  weeks after completing treatment. Though
HCV infection isn’t considered cured  until viral load testing confirms no
measurable viral replication for 24 weeks  following the completion of therapy
(SVR 24), an SVR 12 is highly indicative of  a favored  outcome. 
 
Three patients were dubbed  relapsers—their HCV viral loads rebounded following the completion of 12 weeks  of GS-7977 plus  peg-IFN/RBV therapy.

Overall, Kowdley and his  colleagues report, GS-7977 was well tolerated. The frequency and severity of  side effects were
consistent with those typically associated with peg-IFN/RBV  therapy. The most
common adverse events during the 12 weeks of therapy were  fatigue, headache,
nausea, chills and insomnia.
Source

Slides  @ NATAP

GS-7977 + PEG/RBV in  HCV Genotype 1: The ATOMIC Trial An End To
Response-Guided  Therapy

Headlines

Gilead  Announces Sustained Virologic Response Data for 12-Week Regimen of GS-7977 Plus  Pegylated Interferon and Ribavirin in Genotype 1 

Hepatitis C  PatientsPromising  New Hepatitis C Treatment Tested at Virginia  Mason


Mar 2012

GS-7977-Two more patients relapse in Gilead hepatitis C trial

Gilead Hepatitis C Setback Opens Door to Rivals

Feb 2012

Press release
Feb. 28, 2012, 9:00 a.m. EST
Source

In 2015, Gilead's GS-7977 Plus Ribavirin Will Earn Decision Resources' Proprietary Clinical Gold Standard Status for the Treatment of Non-Responder Patients with Hepatitis C Virus

GS-7977 Plus Ribavirin Will Displace the Current Proprietary Clinical Gold Standard, Telaprevir in Combination with Peg-IFNa/Ribavirin, According to Findings from Decision Resources

BURLINGTON, Mass., Feb 28, 2012 (BUSINESS WIRE) -- Decision Resources, one of the world's leading research and advisory firms for pharmaceutical and healthcare issues, finds that, based on clinical data and the opinions of interviewed thought leaders, telaprevir (Vertex's Incivek, Johnson & Johnson's Incivo) in combination with peg-IFNa (Roche's Pegasys or Merck's Victrelis) and ribavirin (Roche's Copegus; Merck's Rebetol; generics) has earned Decision Resources' proprietary clinical gold standard status for the treatment of non-responder patients with hepatitis C virus (HCV).

Owing to its competitive advantages in safety and tolerability as well as delivery, the interferon-free combination of Gilead's GS-7977 (formerly PSI-7977) plus ribavirin will displace telaprevir plus peg-IFNa/ribavirin and earn proprietary clinical gold standard status for HCV non-responders in 2015, following its launch for the indication in 2014 in the United States.

Decision Resources' analysis of the hepatitis C virus drug market also finds that surveyed U.S. gastroenterologists and managed care organization (MCO) pharmacy directors agree that the percentage of genotype-1 null responders achieving sustained virologic response is one of the attributes that most influences their decisions regarding prescribing and formulary status determinations, respectively, in HCV non-responders.

"Clinical data and the opinions of interviewed thought leaders indicate that several emerging regimens utilizing novel, HCV-specific direct-acting antivirals have advantages over sales-leading telaprevir plus peg-IFNa/ribavirin on this attribute," said Decision Resources Analyst Seamus Levine-Wilkinson, Ph.D. According to insights from surveyed U.S. gastroenterologists and MCO pharmacy directors, the absence of interferon-free treatment options for HCV is one of the greatest unmet needs in HCV.

Clinical data and the opinions of interviewed thought leaders indicate that GS-7977 has demonstrated the potential to significantly fulfill this unmet need. The findings also reveal that surveyed U.S. gastroenterologists indicate that they would prescribe the quadruple regimen of Bristol-Myers Squibb's NS5A inhibitor daclatasvir (BMS-790052) plus Bristol-Myers Squibb's protease inhibitor asunaprevir (BMS-650032) plus peg-IFNa/ribavirin to 41 percent of their HCV non-responder patients.

Decision Resources' forecast for this quadruple regimen is more conservative due to anticipated reimbursement restrictions, positioning in later lines of therapy, competition from IFN-free regimens and competition asunaprevir will face from other protease inhibitors.

The launch of novel HCV-specific agents will increase the size of the drug-treated population mainly as a result of re-treatment of prior non-responders as well as increased referral and drug treatment rates. The overall HCV drug market will experience significant growth, expanding from almost $1.7 billion in 2010 to $14.4 billion in 2015 in the United States, France, Germany, Italy, Spain, the United Kingdom and Japan. Thereafter, the market will decrease to $11.2 billion in 2020, owing to a decline in the size of the treatment-eligible population due to declining prevalence and effective new regimens.

Decision Resources' Robust Market Forecast and Opportunities Analysis Decision Resources provides a comprehensive view of what is happening in a specific drug market now and in the decade ahead. The research includes analysis of the unmet need and near-term drug development opportunities that exist within a drug market powered by primary research from physicians and payers. The robust market forecast and opportunities analysis is comprised of the Pharmacor 2012 advisory service and the DecisionBase 2012 report series.

About Decision Resources Decision Resources ( www.decisionresources.com ) is a world leader in market research publications, advisory services and consulting designed to help clients shape strategy, allocate resources and master their chosen markets. Decision Resources is a Decision Resources Group company. About Decision Resources Group Decision Resources Group is a cohesive portfolio of companies that offers best-in-class, high-value information and insights on important sectors of the healthcare industry. Clients rely on this analysis and data to make informed decisions. Please visit Decision Resources Group at www.DecisionResourcesGroup.com . All company, brand, or product names contained in this document may be trademarks or registered trademarks of their respective holders. SOURCE: Decision Resources Decision Resources Christopher Comfort, 781-993-2597 ccomfort@dresources.com

Copyright Business Wire 2012

New HCV Drug Promising for Difficult-to-Treat Genotype 1 Patients Robust Responses, But Some Treatment Failures; Adverse Events Raise Questions
by Christina Frangou 
Source: IDSE ISSUE: FEBRUARY 2012 | VOLUME: 1

San Francisco—A second Phase IIb study of a new oral therapy for hepatitis C, PSI-7977, taken once daily, increased sustained virologic response (SVR) rates up to 91% in patients with difficult-to-treat hepatitis C virus (HCV) genotype 1 infection—a substantial improvement from the 50% reported in patients who received standard peginterferon and ribavirin (Peg-IFN/RBV) therapy. The study also showed significant advantages of PSI-7977 in patients who typically have poor responses to interferon.

Investigators say the new drug has the potential to dramatically alter the treatment paradigm for patients with hepatitis C virus (HCV) infection. “That’s true for all genotypes and all patients,” said lead author Eric J. Lawitz, MD, medical director of Alamo Medical Research, in San Antonio.
Patients who have the interleukin-28B (IL28B) TT genotype generally have a much lower chance of responding to IFN than people with the CC or CT genotypes. Yet in this study, these patients achieved high SVR rates to PSI-7977. Of the 13 patients who carried the TT allele, all tested negative for HCV by the third week of treatment and achieved SVR at week 12.
“The high SVR of greater than 90% in HCV genotype 1 patients was independent of predictors of poor IFN response,” Dr. Lawitz said.

The trial—known as PROTON—was the second Phase IIb study of PSI-7977 presented at The Liver Meeting 2011. In the first study, the ELECTRON study, investigators reported that 100% of patients who received PSI-7977 without IFN achieved an SVR (see “New Polymerase Inhibitor Could Become Cornerstone of Interferon-free HCV Treatment Regimen”).

Results from the two studies sparked considerable excitement among attendees of The Liver Meeting about this investigational therapy.

“I think it’s proof of principle that the proper combination of direct-acting antivirals can, in fact, produce enough suppression of viral replication to result in extinction of infection without the benefit of a broadly acting antiviral like IFN,” said Raymond Chung, MD, chief of hepatology and vice-chief of gastroenterology at Massachusetts General Hospital, in Boston.
The PROTON study was designed to examine dose-dependent response rates for PSI-7977 in HCV genotype 1–infected patients. Investigators enrolled 121 treatment-naive patients with this genotype in a randomized, double-blind, placebo-controlled, dose-ranging fashion. All patients were at least 18 years old with an HCV RNA level of 50,000 IU/mL or greater, platelets greater than 90,000/mm3, neutrophils greater than 1,500/mm3, and a hemoglobin level of at least 11 g/dL, with no evidence of cirrhosis.

Trial participants were randomized in a 2:2:1 ratio to one of three treatment arms: PSI-7977 200 or 400 mg daily in combination with IFN and RBV (n=48 and n=47, respectively) or Peg-IFN/RBV alone (n=26). Patients in the PSI-7977 arms received triple therapy for 12 weeks, followed by an additional 12 weeks of Peg-IFN/RBV. All patients who achieved early rapid virologic response (RVR) discontinued therapy at 24 weeks, while all others continued therapy for a total of 48 weeks. Patients in the IFN and RBV arm received treatment for 48 weeks.

Analysis showed robust response rates among all PSI-7977 patients regardless of dose. Patients who received 200 mg daily showed an RVR rate of 98%, an early RVR rate of 98% and an end-of-treatment response rate of 91%. Patients receiving 400 mg showed a 98% RVR, 91% early RVR and 91% end-of treatment response through 24 weeks. In contrast, response rates among patients who received Peg-IFN/RBV alone were 19%, 50% and 50%, respectively.

In an as-treated analysis of patients who received at least eight weeks of PSI-7977, 88% of those in the 200-mg arm and 98% of those in the 400-mg arm achieved an SVR at 12 weeks.

Several failures occurred in the trial.
Three patients in the 200-mg arm who had viral suppression during the first 12 weeks of treatment with PSI-7977 experienced a virologic breakthrough during the follow-up treatment period with Peg-IFN/RBV. No breakthroughs were observed among patients in the 400-mg arm, although one patient had a viral relapse before SVR at 4 weeks. “This suggests that [the] 400-mg dose achieved a deeper viral suppression,” said Dr. Lawitz.

The extent of viral suppression may be the key difference between the 200- and 400-mg doses of PSI-7977, he said. PSI-7977 at a 400-mg dose may provide a more thorough viral suppression with lower risk for virologic breakthrough. Patients in both groups quickly became negative for HCV RNA after PSI-7977 was started, but patients who received the 200-mg dose had more virologic breakthroughs after the PSI-7977 therapy was completed. No patient in either treatment arm developed an S282T mutation.

Investigators said they were pleased to see that the adverse events reported in the PROTON trial were typical of those seen with Peg-IFN/RBV treatment, except for a small increase in insomnia. Overall, 15% of patients in the 400-mg arm and 8% of those in the Peg-IFN/RBV–only arm reported insomnia.

More cases of neutropenia occurred with PSI-7977 than with Peg-IFN/RBV, but it was unlikely that the difference was significant, said the investigators. Three patients who received PSI-7977 had grade IV neutropenia compared with none in the Peg-IFN/RBV arm. However, the numbers of patients were too low to result in meaningful conclusions.

Still, experts say more patients must be studied to confirm that the new drug is safe.

“The numbers for neutropenia and anemia are confusing to me. They are small numbers but I’m still not certain about the safety of this compound,” said Paul Pockros, MD, head of gastroenterology and hepatology, and director of the Center for Liver Diseases, Scripps Clinic, in La Jolla, Calif.
The study was not powered to detect differences in neutropenia and anemia between the three groups, but differences would be statistically significant if 1,000 patients had participated in the trial, Dr. Pockros explained. “Is this drug going to be safe in 1,000 patients?” he asked.

Dr. Lawitz said investigators would expect to see a difference in adverse events between the 200- and 400-mg arms in this trial if PSI-7977 increased the risk for neutropenia, but that was not the case, with more neutropenia and anemia occurring in the patients receiving the lower dose.
“To me, that suggests that this is a trial with small numbers, and when we get larger numbers the difference is probably not going to be significant,” he said.

PSI 7977, in combination with RBV as dual therapy, is set to enter Phase III trials

Hard-to-Treat Group Trips Up HCV Drug
By Michael Smith, North American Correspondent,
MedPage Today
Published: February 17, 2012
A promising hepatitis C medication has run into a roadblock in a small group of hard-to-treat patients, according to the drug's maker.

The drug, dubbed GS-7977, was being used with a standard drug, ribavirin, but without the other standby, pegylated interferon, to treat 10 patients with genotype one virus, according to Gilead Sciences.
But after a good early response in eight patients, six of them relapsed within a month of finishing the 12-week therapy. The remaining two have not relapsed but have just finished treatment, the company said.
In a conference call, company officials said the results were unexpected but will not derail the drug, which has been shown to be safe and effective in some groups of hepatitis C patients.

The patients who relapsed were so-called "null responders" who had previously been treated with the standard ribavirin and interferon, but who had not cleared the virus.

They are a "challenging patient population to cure," said Norbert Bischofberger, PhD, Gilead's chief scientific officer.

The drug is also being tested, using the same approach, in patients who have not previously been treated and in patients with genotypes two and three of the virus, who are easier to treat.
Preliminary data in the genotype two and three patients, presented last year, showed that 10 of 10 had been cured. Data on the treatment-naive patients is to be presented next month.

The finding in the null responders has "answered an important question," according to Gilead CEO John Milligan, PhD, and hints that in some patient groups more than one direct-acting agent may be needed for a cure.

Bischofberger told those on the conference call that it's also possible, in his opinion, that the 12-week duration of treatment was simply not long enough to knock the virus down.
The direct-acting agents, which target elements of the virus itself, are a new departure in hepatitis C therapy, which for years has relied on boosting the immune system overall using ribavirin and interferon.
GS-7977 is a nucleotide analog polymerase inhibitor; other drugs, both approved and under development, attack the viral protease enzyme or other targets.

But the advent of the direct-acting agents has sparked a push to stop using interferon, which is difficult for many patients to tolerate, and some studies have suggested that a combination of the new agents would work well without the older drug.

In this case, exactly why such a high percentage of the patients relapsed remains unclear, Milligan said, reminding those on the call that the data are "preliminary results" in only eight patients.

Source-Medpage Today

Gilead Announces Data for Genotype 1 Null Responder Hepatitis C Patients Enrolled in ELECTRON Study    – Viral Relapse Seen Post Treatment with GS-7977 Plus Ribavirin – – Awaiting Data for Treatment-Naïve Genotype 1 Patients –   FOSTER CITY, Calif.--(BUSINESS WIRE)--Feb. 17, 2012--
 
Gilead Sciences, Inc. (NASDAQ:GILD) announced today that the majority of hepatitis C genotype 1 patients with a prior “null” response to an interferon (IFN)-containing regimen enrolled in the ongoing ELECTRON study experienced viral relapse within four weeks of completing 12 weeks of treatment with GS-7977 plus ribavirin (RBV). Ten patients were randomized to this arm of the ELECTRON study and data are available for eight of the 10 patients at this time. Among these eight patients, six have experienced viral relapse. Two patients have not relapsed; however, they have only reached the two week post-treatment time point.

“These data answer an important question about the use of GS-7977 and ribavirin for the treatment of genotype 1 null responder patients, suggesting that additional direct acting antivirals may be necessary to effectively treat this patient population,” said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer. “We will continue to explore a number of therapeutic approaches to address this significant unmet medical need, including combinations with other oral antivirals.”

GS-7977 is a nucleotide analog polymerase inhibitor that is currently being studied for the treatment of chronic hepatitis C. A number of ongoing Phase 2 and Phase 3 studies are evaluating the safety and efficacy of the compound with and without RBV and/or pegylated interferon (Peg-IFN) in patients with genotypes 1-6 who are treatment naïve, treatment experienced, or have had a “null” response to Peg-IFN.


Genotype 2 and 3 data from the ELECTRON study were presented at the 62nd annual meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2011). Data from the genotype 1 null responder arm of the study will be presented at an upcoming scientific conference.
Results from ongoing studies in genotype 1 treatment-naïve patients will be available in the coming months. The first data evaluating GS-7977 plus RBV for 12 weeks in genotype 1 naïve patients will come from an arm of the QUANTUM study with 25 patients at the end of the first quarter of 2012. This will be followed in the second quarter by data from the ELECTRON study involving 25 patients and, early in the third quarter, data on GS-7977 and RBV treatment for 24 weeks from an arm of the QUANTUM study will become available.

Conference Call
Gilead will host a conference call today, February 17, 2012 at 8:00 a.m. Eastern Time, to discuss these study results. To access the live call, please dial 1-866-825-1709 (U.S.) or 1-617-213-8060 (international). The conference passcode number is 71588571. Telephone replay is available approximately one hour after the call through 11:59 p.m. Eastern Time, February 20, 2012. To access, please call 1-888-286-8010 (U.S.) or 1-617-801-6888 (international). The conference passcode number for the replay is 64278864. The information provided on the teleconference is only accurate at the time of the conference call, and Gilead will take no responsibility for providing updated information.

About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Asia Pacific.

Forward-Looking Statement
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors, including the possibility of unfavorable results from the ELECTRON and QUANTUM studies, including in genotype 1 treatment-naïve patients, as well as other clinical trials evaluating GS-7977 with or without RBV and/or Peg-IFN or in combination with other antivirals; the anticipated timing for receiving clinical data and making regulatory filings; and Gilead’s ability to develop an all-oral antiviral regimen for HCV genotype 1 patients or a pangenotypic regimen for all HCV patients. As a result, GS-7977 may never be successfully commercialized. Further, Gilead may make a strategic decision to discontinue development of GS-7977 if, for example, it believes commercialization will be difficult relative to other opportunities in its pipeline. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2011, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

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

Source: Gilead Sciences, Inc.
Gilead Sciences, Inc.
Susan Hubbard, 650-522-5715 (Investors)
Amy Flood, 650-522-5643 (Media)