Bristol-Myers Squibb Presents Phase III Data Demonstrating that Investigational All-oral Daclatasvir and Asunaprevir Therapy Achieved SVR12 Rates of up to 90% Among Broad Range of Genotype 1b Hepatitis C Patients

• Results of the HALLMARK-Dual study include data among genotype 1b cirrhotic and non-cirrhotic, treatment-naïve, non-responder, and peginterferon/ribavirin ineligible and intolerant patients
• Study reinforces the potential of daclatasvir-based regimens to treat HCV patients with high unmet needs
• Data to be presented during late-breaker session at EASL The International Liver Congress^TM

Category: R&D News

Thursday, April 10, 2014 7:00 am EDT

"Daclatasvir has unique scientific characteristics that support ongoing research for its use in multiple all-oral HCV regimens"

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced Phase III results from the global HALLMARK-Dual study investigating the all-oral, interferon- and ribavirin-free regimen of daclatasvir (DCV), a NS5A inhibitor, and asunaprevir (ASV), a NS3 inhibitor, among genotype 1b hepatitis C virus (HCV) infected patients. Results showed that the 24-week regimen achieved an overall sustained virologic response (a functional cure) 12 weeks after the end of treatment (SVR₁₂) among treatment-naïve (90%), peginterferon/ribavirin non-responder (82%), and peginterferon/ribavirin ineligible/intolerant (82%) patients, including cirrhotic and non-cirrhotic patients (84% and 85%). In the study the DCV+ASV regimen was generally well tolerated. These data will be presented this week at the 49th annual meeting of the European Association for the Study of the Liver (EASL) The International Liver Congress^TM in London, April 9-13.

Globally, there are 170 million people infected with HCV, with genotype 1 being the most prevalent. There are 9 million people infected in Europe, where there is a high prevalence of HCV genotype 1b.

“Not only was the daclatasvir and asunaprevir regimen highly effective among study participants, it was also very well tolerated, even among sicker patients with more advanced liver disease and higher unmet needs,” said lead study investigator Professor Michael P. Manns, director of the Department of Gastroenterology, Hepatology and Endocrinology at Hannover Medical School, Germany. “Despite a rapidly evolving HCV treatment paradigm, physicians and patients remain in need of new all-oral, interferon- and ribavirin-free regimens that have the potential to achieve virologic cure across a broad range of patients, including those with advanced liver disease and cirrhosis.”

These data were part of the company’s recent DCV and ASV new drug application (NDA) submissions to the U.S. Food and Drug Administration (FDA), and helped support the validated marketing authorization application to the European Medicines Agency for the use of DCV in combination with other agents for the treatment of adults with HCV with compensated liver disease, including genotypes 1, 2, 3, and 4. These data are comparable to a similar Phase III study of this regimen in Japanese patients, which led to the submission of a New Drug Application with Japan’s Pharmaceutical and Medical Devices Agency.

“Daclatasvir has unique scientific characteristics that support ongoing research for its use in multiple all-oral HCV regimens,” said Brian Daniels, MD, senior vice president, Global Development and Medical Affairs, Research and Development, Bristol-Myers Squibb. “In addition to the HALLMARK-Dual study, we are pleased to be presenting data at EASL on our investigational 3DAA fixed-dose-combination, as well as daclatasvir in combination with other HCV compounds.”

Study Design and Results

This Phase III multinational clinical trial involved 116 sites in 18 countries, including countries that have a high prevalence of genotype 1b such as Korea and Taiwan. In the study, treatment-naïve patients (n=205) received DCV 60 mg once daily plus ASV 100 mg twice daily for 12 weeks, and 102 patients received matching placebo for 12 weeks. The DCV+ASV treatment-naïve group continued treatment through week 24; placebo recipients entered another DCV+ASV study. The peginterferon/ribavirin-ineligible/intolerant (n=235) and non-responder patients (n=205) received the same doses of DCV and ASV for 24 weeks. The primary endpoint was the percentage of patients with a sustained virologic response at 12 weeks after the end of treatment (SVR₁₂).

Virologic Response

• 90% of treatment-naïve patients achieved SVR₁₂
• 82% of patients with prior null or partial response to peginterferon/ribavirin (non-responders) achieved SVR₁₂
• 82% of peginterferon/ribavirin ineligible/intolerant patients achieved SVR₁₂
  • Among peginterferon/ribavirin ineligible/intolerant patients, SVR₁₂ was achieved by patients with anemia/neutropenia (91%); depression (80%) and compensated advanced fibrosis/cirrhosis with thrombocytopenia (73%).

Results among Cirrhotic Patients treated with DCV+ASV

• At baseline, 33 treatment-naïve, 63 non-responders, and 111 ineligible/intolerant patients had cirrhosis. Cirrhotic patients made up ~32% of the study population.

• SVR rates were similar in cirrhotic (84%) and non-cirrhotic (85%) patients.

The regimen used in this Phase III study resulted in low rates of discontinuation (1-3%) due to adverse events (AEs). In addition, the rate of serious adverse events (SAEs) was low (5-7%). Headache was the most common AE in the study (24-25%). No deaths occurred, and no clinically meaningful differences were observed in frequencies of SAEs, AEs leading to discontinuation, or grade 3/4 ALT/AST (liver enzymes) elevations in patients with or without cirrhosis. Importantly, all grade 3/4 ALT/AST elevations observed were reversible and resolved off-treatment.

About Hepatitis C

Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. Up to 90 percent of those infected with hepatitis C will not spontaneously clear the virus and will become chronically infected. According to the World Health Organization, up to 20 percent of people with chronic hepatitis C will develop cirrhosis; of those, up to 25 percent may progress to liver cancer.

About Bristol-Myers Squibb’s HCV Portfolio

Bristol-Myers Squibb’s research efforts are focused on advancing late-stage compounds to deliver the most value to patients with hepatitis C. At the core of our pipeline is daclatasvir (DCV), an investigational NS5A replication complex inhibitor that has been studied in more than 5,500 patients as part of multiple direct-acting antiviral (DAA) based combination therapies. DCV has shown a low drug-drug interaction profile, supporting its potential use in multiple treatment regimens and in people with co-morbidities.

Daclatasvir is being investigated in combination with sofosbuvir in high unmet need patients, such as pre- and post-transplant patients, HIV/HCV co-infected patients, and patients with genotype 3, as part of the ongoing Phase III ALLY Program.

In 2014, the U.S. Food and Drug Administration (FDA) granted Bristol-Myers Squibb’s investigational DCV Dual Regimen Breakthrough Therapy Designation for use as a combination therapy in the treatment of genotype 1b HCV infection.

In 2013, Bristol-Myers Squibb’s investigational all-oral 3DAA Regimen (daclatasvir/ asunaprevir/BMS-791325) also received Breakthrough Therapy Designation, which helped to expedite the start of the ongoing Phase III UNITY Program. Study populations include non-cirrhotic naïve, cirrhotic naïve and previously treated patients. The daclatasvir 3DAA regimen is being studied as a fixed-dose-combination treatment with twice daily dosing.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

Bristol-Myers Squibb Forward Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that clinical trials of these compounds will support regulatory filings, or that DCV or any other compounds mentioned in this release will receive regulatory approval or, if approved, that they will become commercially successful products. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2013 in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

EASL The International Liver Congress is a registered trademark of European Association for the Study of the Liver.

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Merck Announces Results from Studies Evaluating Investigational Hepatitis C Treatments, MK-5172 and MK-8742, in Treatment-Naïve Patients with Genotype 1 Infection

Clinical Findings Support Advancement into Phase 3 Trials 

Thursday, April 10, 2014 1:00 am EDT

WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside of the United States and Canada, today announced additional data from the ongoing C-WORTHy study, a multi-arm Phase 2 clinical trial evaluating the efficacy and safety of a once-daily, all-oral regimen combining MK-5172, an investigational hepatitis C virus (HCV) NS3/4A protease inhibitor, and MK-8742, an investigational HCV NS5A replication complex inhibitor, among patients with chronic HCV Genotype 1 infection (GT1). In an interim analysis of treatment-naïve, non-cirrhotic patients administered a 12-week regimen of MK-5172/MK-8742, with and without ribavirin (RBV), a sustained viral response¹ (SVR) was observed in 98 percent (42/43) of patients administered MK-5172/MK-8742 alone and 94 percent (75/80) in those administered MK-5172/MK-8742 plus RBV. These data were presented, along with data on an 8-week regimen, at the 49th Annual Meeting of the European Association for the Study of the Liver (EASL), also known as The International Liver Congress™ 2014, in London, UK.

“These Phase 2 results add to growing evidence for the potential efficacy of MK-5172 and MK-8742 for treatment of chronic HCV infection,” said Dr. Eliav Barr, vice president, Infectious Diseases, Merck Research Laboratories. “These findings are integral to advancing our research of these investigational candidates into C-EDGE, the Phase 3 clinical program that will seek to more broadly evaluate the potential of MK-5172/MK-8742 in diverse patient populations.”

C-WORTHy Study Design

C-WORTHy is a two-part, parallel-group, randomized (within group) clinical trial evaluating a range of subpopulations of patients with HCV GT1 infection. The study evaluated different treatment durations of MK-5172 (100 mg once daily) plus MK-8742 (50 mg once daily), with or without RBV. A total of 471 patients with HCV GT1 RNA levels of ≥10,000 IU/mL were enrolled in C-WORTHy across 16 arms.

Key Findings for MK-5172/MK-8742

The interim results presented were from treatment-naïve, non-cirrhotic patients who received one of 3 regimens: A) MK-5172/MK-8742 + RBV for 8 weeks (N=30), B) MK-5172/MK-8742 + RBV for 12 weeks (N=85), and C) MK-5172/MK-8742 (without RBV) for 12 weeks (N=44), (see table 1).

Table 1 – Interim Results from the C-WORTHy Trial Showing Treatment-Naïve, Non-Cirrhotic Patients with HCV GT1 Infection (Intention-to-Treat (ITT) Analysis)

Parameter			MK-5172 + MK-8742 (NO RBV) (12 Weeks) (N =44)			MK-5172 + MK-8742 + RBV (12 Weeks) (N = 85)			MK-5172 + MK-8742 + RBV (8 Weeks) (N =30)
SVR4-24†, % (n)			98% (43)			94% (80)			83% (25)
No SVR, % (n)
Breakthrough			0			1% (1)			0
Relapse			2% (1)			1% (1)			17% (5)
Non-virologic Discontinuation			0			4% (3)			0
By Sub-genotype
GT1a			97% (29)			94% (49)			83% (25)
GT1b§			100% (14)			94% (31)			--
† Part A: 100% of patients completed Follow-up week (FU)24; Part B: 8 week arm: 93% have completed FU8; 12 week arm: 100% of patients have completed FU4; 2 patients (Part A) and 1 patient (Part B) discontinued early and are counted as failures. § Two patients with GT1 (non-a, non-b) were enrolled; these are analyzed with GT1b.

Among the five patients who relapsed in the eight-week regimen arm of PN035B, two patients had very low MK-5172 and MK-8742 levels during the course of therapy. The relationship between this finding and the relapse is being investigated.

The most common adverse events recorded in the RBV and RBV-free treatment groups, respectively, were fatigue (32%, 23%), headache (20%, 33%), nausea (21%, 16%), diarrhea (13%, 9%) and insomnia (13%, 7%). There were no early discontinuations due to drug-related adverse events and no clinically significant abnormalities detected in routine laboratory analysis of hematologic markers.

PN038 Study Design and Findings

Additionally, new data from PN038, a Phase 2 dose-ranging clinical trial evaluating MK-5172 once-daily with peginterferon alfa-2b and ribavirin (PR, weekly), were presented, evaluating SVR24 in treatment-naïve, non-cirrhotic patients with GT1 infection. PN038 is a Phase 2 clinical trial investigating the efficacy and safety of MK-5172 doses (25 mg, 50 mg, and 100 mg) once-daily with PR over a 12-week treatment cycle in GT1 treatment-naïve, non-cirrhotic patients (n=87). The analysis presented was ITT, in which all patients who did not achieve SVR (including those who dropped out for non-virologic reasons), were recorded as failures.

MK-5172 at doses of 50 mg and 100 mg with PR for 12 weeks of treatment achieved SVR24 rates of 75.0 percent (21/28) and 83.3 percent (25/30), respectively, supporting use of MK-5172 below 100 mg dose (see table 2).

Table 2: PN038 Virologic Responses – (ITT Analysis)

Patients with HCV RNA <25 IU/mL / total # of patients (%)

MK-5172 25 mg with PR (N=29)

MK-5172 50 mg with PR (N=28)

MK-5172 100 mg with PR (N=30)

TW*4

93.1% (27/29)

96.4% (27/28)

100.0% (30/30)

TW12

93.1% (27/29)

96.4% (27/28)

96.7% (29/30)

SVR12

48.3% (14/29)

75.0% (21/28)

86.7% (26/30)

SVR24

48.3% (14/29)

75.0% (21/28)

83.3% (25/30)

*Treatment week

The most common recorded adverse experiences recorded across all treatment arms were: fatigue (61%), headache (46%), nausea (43%), and decreased appetite (43%). These adverse experiences did not appear to be dose-related.

One patient discontinued therapy after seven days of dosing with MK-5172 100 mg, plus PR and experienced muscle inflammation (creatine kinase >5x upper limits of normal [ULN]), elevated transaminases to >3x ULN, and total bilirubin >2x ULN, associated with a positive toxicology screen for ethanol. There were no other clinically significant transaminase elevations recorded in this study.

About Merck’s Phase 3 HCV Program: C-EDGE

Based on the results of the Phase 2 clinical program, Merck has initiated Phase 3 clinical trials for MK-5172/MK-8742. The Phase 3 program, called C-EDGE, will evaluate the safety and efficacy of MK-5172/MK-8742 with and without ribavirin in various genotypes and across a broad range of patient populations with chronic HCV. Study cohorts will include: C-EDGE TN (GT1, GT4-6; treatment-naive ± cirrhosis), C-EDGE CO-INFXN (GT1, GT4-6; treatment-naive ± cirrhosis with HIV/HCV co-infection), C-EDGE RECOVERY (GT1, GT4-6; treatment-naive ± cirrhosis; ± HIV/HCV co-infection on opiate substitution therapy), and C-EDGE TE (GT1, GT4-6; prior failed treatment with peginterferon/ribavirin; ± HIV/HCV co-infection). Study information can be found at www.clinicaltrials.gov.

Merck’s Commitment to HCV

For more than 25 years, Merck has been at the forefront of the response to the HCV epidemic. Merck employees are dedicated to applying their scientific expertise, resources and global reach to deliver healthcare solutions that support people living with HCV worldwide.

About Merck

Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside of the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.

Merck Forward-Looking Statement

This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Merck’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Merck’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2013 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

¹ Defined as HCV RNA below the limit of quantification or below the limit of detection at the last visit on record – 4, 8, 12, or 24 weeks after the completion of therapy

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Gilead Announces Results from Study of Sovaldi® for Retreatment of Chronic Hepatitis C in Patients Not Cured with Prior Antiviral Therapy

-- Results Demonstrate Efficacy of Sovaldi-Based Regimen in GT1 Infected Patients Who Failed Prior Therapy with Other Direct Acting Antivirals--

-- Data Support Retreatment with Sovaldi-Based Regimen in GT2 or GT3 Infected Patients Who Failed Prior Treatment with Sovaldi --

LONDON--(BUSINESS WIRE)--Apr. 10, 2014-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced results from an open-label clinical trial (Study GS-US-334-0109) evaluating once-daily Sovaldi^® (sofosbuvir) 400 mg tablets for the retreatment of chronic hepatitis C virus (HCV) infection among patients who failed prior therapy. These data will be presented in two oral sessions at the 49th Annual Meeting of the European Association for the Study of the Liver (The International Liver Congress 2014) in London.

In Study GS-US-334-0109 (Oral #55), patients with genotype 1 HCV infection (n=80) received 12 weeks of treatment with once-daily Sovaldi plus weight-based ribavirin (RBV) twice-daily (1,000 or 1,200 mg/day) and pegylated interferon (peg-IFN; 180 μg/week). Patients in the study had failed prior regimens containing peg-IFN, RBV and an investigational NS3 protease inhibitor, with or without investigational direct-acting antivirals (DAAs) (NS5A and/or non-nucleoside NS5B inhibitors). Forty-five percent of patients (n=36) had received more than one course of prior therapy, and 90 percent (n=72) had at least one viral mutation associated with HCV NS3, NS5A or NS5B drug resistance.

Among the 50 patients for whom sustained virologic response data was available 12 weeks after the end of treatment (SVR12), 74 percent (n=37/50) achieved SVR12. Additionally, 80 percent (n=28/35) of patients with baseline resistance against two or more DAAs achieved SVR12.

“This study demonstrates that Sovaldi-based regimens can achieve high cure rates even among hepatitis C patients who previously failed therapy with baseline resistance to at least two DAAs,” said Stanislas Pol, MD, PhD, Professor of Hepatology and Gastroenterology, Paris Descartes University, Paris, France, and a principal investigator. “Importantly, Sovaldi has now demonstrated efficacy among genotype 1 HCV infected patients who failed prior treatment with three or four drug regimens and have developed viral resistance to some of the components of those regimens.”

In a separate presentation (Oral #8), retreatment with Sovaldi in genotype 2 (n=11) or genotype 3 (n=96) HCV infected patients who previously failed treatment with 12 or 16 weeks of Sovaldi plus RBV in the Phase 3 studies FISSION, FUSION and POSITRON was evaluated. Thirty-six percent of these patients (39/107) had cirrhosis. Patients were retreated either with a 12-week regimen of Sovaldi, RBV and peg-IFN, or a 24-week, interferon-free regimen of Sovaldi plus RBV. The choice of regimen was determined by study investigators.

Among patients with available SVR12 data, 63 percent (n=25/40) of those who received the 24-week all-oral regimen and 92 percent (n=24/26) of those who received the 12-week regimen of Sovaldi, RBV, and peg-IFN achieved SVR12.

“These data support initial findings from the Phase 3 trials, which demonstrate that Sovaldi is an effective treatment option and one that may also be particularly important for genotype 2 and 3 patients who failed a previous sofosbuvir-based regimen,” said Rafael Esteban, MD, Head of the Internal Medicine and Liver Unit, Hospital Universitari Vall d’Hebron and Professor of Medicine, Universitat Autónoma de Barcelona, Barcelona, Spain and a principal investigator for the study.

Sovaldi was well tolerated in Study GS-US-334-0109. The most common adverse events were consistent with the safety profiles of peg-IFN and/or RBV. Additional information about the study can be found at www.clinicaltrials.gov.

About Sovaldi

Sovaldi is an oral nucleotide analog inhibitor of the HCV NS5B polymerase enzyme, which plays an essential role in HCV replication. Sovaldi is a direct-acting agent, meaning that it interferes directly with the HCV life cycle by suppressing viral replication.

Sovaldi was approved in the United States on December 8, 2013 and in the European Union on January 17. In the United States, Sovaldi is approved for the treatment of chronic hepatitis C infection as a component of a combination antiviral treatment regimen. Efficacy has been established in subjects with HCV genotype 1, 2, 3 or 4 infection, including those with hepatocellular carcinoma meeting Milan criteria (awaiting liver transplantation) and those with HCV/HIV-1 co-infection. Treatment response varies based on baseline host and viral factors. Monotherapy is not recommended for treatment of chronic hepatitis C. Study GS-US-334-0109 evaluated investigational uses of Sovaldi, for which safety and efficacy have not yet been established.

IMPORTANT SAFETY INFORMATION

Contraindications

Sovaldi combination treatment with ribavirin or with peginterferon alfa plus ribavirin is contraindicated in women who are pregnant or may become pregnant and men whose female partners are pregnant because of the risk for birth defects and fetal death associated with ribavirin. Contraindications to peginterferon alfa and ribavirin also apply to Sovaldi combination treatment. Refer to the prescribing information of peginterferon alfa and ribavirin for a list of their contraindications.

Warnings and Precautions

• Pregnancy: Use with Ribavirin or Peginterferon Alfa/Ribavirin: Ribavirin therapy should not be started unless a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Female patients of childbearing potential and their male partners must use two forms of non-hormonal contraception during treatment and for at least 6 months after treatment has concluded. Routine monthly pregnancy tests must be performed during this time. Refer to the prescribing information for ribavirin.

• Use with Potent P-gp Inducers: Rifampin and St. John’s wort should not be used with Sovaldi as they may significantly decrease sofosbuvir plasma concentration, reducing its therapeutic effect.

Adverse Reactions

Most common (≥20 percent, all grades) adverse reactions for:

• Sovaldi + peginterferon alfa + ribavirin combination therapy were fatigue, headache, nausea, insomnia, and anemia
• Sovaldi + ribavirin combination therapy were fatigue, and headache

Drug Interactions

In addition to rifampin and St. John’s wort, coadministration of Sovaldi is not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of sofosbuvir, reducing its therapeutic effect.

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 and South 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 longer-term results from clinical trials evaluating Sovaldi for the treatment or retreatment of HCV, and the risk that healthcare providers, payers or insurers may not recognize the benefits of Sovaldi. As Sovaldi is used over longer periods of time by treatment-experienced patients with underlying health problems taking numerous other medicines, Gilead may find new issues such as safety, resistance or drug interaction issues, which may require it to provide additional warnings or contraindications in the label, which could reduce the market acceptance of Sovaldi. 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 Annual Report on Form 10-K for the year ended December 31, 2013, 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.

U.S. full prescribing information for Sovaldi is available at www.gilead.com.

Sovaldi is a registered trademark of Gilead Sciences, Inc.

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.

Source: Gilead Sciences, Inc.

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Gilead Announces Phase 2 Results for Two Investigational All-Oral Sofosbuvir-Based Regimens for the Treatment of Chronic Hepatitis C

-- Data Support Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination with Ribavirin in Genotype 3 HCV; Product Under Regulatory Review for Genotype 1 in U.S., Europe --

-- Combination of Sofosbuvir and GS-5816 Demonstrates Efficacy Against HCV Genotypes 1-6 --

LONDON--(BUSINESS WIRE)--Apr. 10, 2014-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced data from two Phase 2 studies evaluating investigational all-oral regimens containing the nucleotide analog polymerase inhibitor sofosbuvir (SOF) for the treatment of chronic hepatitis C virus (HCV) infection. These data are being presented this week at the 49th Annual Meeting of the European Association for the Study of the Liver (The International Liver Congress 2014) in London.

The first study, ELECTRON2 (Oral #6), is an ongoing, open-label Phase 2 clinical trial evaluating a once-daily fixed-dose combination of SOF 400 mg and the NS5A inhibitor ledipasvir (LDV) 90 mg, with and without ribavirin (RBV) twice-daily (1,000 or 1,200 mg/day), among HCV-infected patient populations.

In this study, 100 percent (n=26/26) of treatment-naïve genotype 3 patients receiving 12 weeks of LDV/SOF plus RBV and 64 percent (n=16/25) of treatment-naïve genotype 3 patients receiving 12 weeks of LDV/SOF without RBV achieved a sustained virologic response 12 weeks after completing therapy (SVR12). Among genotype 1-infected patients who had failed prior treatment with SOF plus RBV, 100 percent (19/19) achieved SVR12 following 12 weeks of LDV/SOF plus RBV. Additionally, 65 percent (n=13/20) of genotype 1-infected patients with decompensated or Child-Turcotte-Pugh Class B cirrhosis receiving 12 weeks of LDV/SOF without RBV achieved SVR12. LDV/SOF with and without RBV was well-tolerated, including among patients with more advanced liver disease.

“The ELECTRON2 data suggest that an all-oral regimen of LDV/SOF plus RBV has the potential to provide high cure rates for genotype 3 patients in just 12 weeks – half the duration of current all-oral treatment regimens,” said Professor Edward Gane, MD, Deputy Director and Hepatologist, New Zealand Liver Transplant Unit, Auckland City Hospital in New Zealand, and principal investigator of the ELECTRON2 study. “These results also suggest that LDV/SOF may be an effective treatment regimen for HCV genotype 1-infected patients who have failed a previous sofosbuvir-based regimen and those with advanced liver disease, including decompensated cirrhosis.”

A second study, Study GS-US-342-0102 (Oral #111), is an ongoing randomized Phase 2 clinical trial in which treatment-naïve, non-cirrhotic patients with genotypes 1-6 HCV infection received a 12-week course of SOF plus the pan-genotypic NS5A inhibitor GS-5816. Patients received SOF 400 mg and either GS-5816 25 mg (n=77) or GS-5816 100 mg (n=77). In this study, 94.8 percent (n=73/77) of patients receiving the 25 mg dose of GS-5816 and 96.1 percent (n=74/77) of patients receiving the 100 mg dose achieved SVR12.

“The results of this study of sofosbuvir with a new pan-genotype NS5A inhibitor demonstrate the curative potential of this combination,” said Gregory T. Everson, MD, Professor of Medicine and Director, Section of Hepatology, University of Colorado, Denver, and principal investigator of Study GS-US-342-0102. “The combination was not only effective across all genotypes and patient subgroups, but also was well tolerated. These results warrant additional study in future trials, with the hope of providing a potent, pan-genotypic combination with few side effects and a high chance for cure.”

The most common adverse events occurring in more than 10 percent of patients were fatigue, headache and nausea. There were no treatment discontinuations due to adverse events, and no evidence of treatment-related laboratory abnormalities.

Additional information about ELECTRON2 and GS-US-342-102 can be found at www.clinicaltrials.gov.

About SOF-Based Fixed-Dose Combinations

Full data from three Phase 3 clinical trials of the LDV/SOF fixed-dose combination (ION-1, ION-2 and ION-3) are also being presented at The International Liver Congress 2014. Gilead announced topline results from the ION studies on December 18, 2013. On February 10, 2014, Gilead submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for the LDV/SOF fixed-dose combination tablet for the treatment of genotype 1 HCV infection in adults. The FDA has assigned the product a Breakthrough Therapy designation, which is granted to investigational medicines that may offer major advances in treatment over existing options. On April 7, 2014, the company announced that the FDA has granted the application a priority review, setting a target action date under the Prescription Drug User Fee Act (PDUFA) of October 10, 2014.

On March 27, 2014, the European Medicines Agency (EMA) accepted Gilead’s request for accelerated assessment for LDV/SOF, a designation that is granted to new medicines of major public health interest. Accelerated assessment could shorten the EMA’s review time of LDV/SOF by two months, although it does not guarantee a positive opinion from the Committee for Medicinal Products for Human Use, or final approval by the European Commission.

Gilead has developed a once-daily fixed-dose combination tablet containing SOF and GS-5816. A second Phase 2 clinical trial (Study GS-US-342-0109) evaluating 12 weeks of SOF plus GS-5816, with or without RBV, among treatment-experienced cirrhotic and non-cirrhotic patients with genotypes 1 or 3 HCV infection is ongoing. Pending full results from Studies GS-US-334-102 and GS-US-342-0109, Gilead plans to initiate Phase 3 studies evaluating the efficacy and safety of the SOF/GS-5816 fixed-dose combination.

LDV/SOF and SOF/GS-5816 are investigational products and their safety and efficacy have not yet been established.

SOF as a single agent is approved as Sovaldi^® in the United States, European Union, Canada, New Zealand and Switzerland.

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 and South 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 risk that the FDA, European Commission and other regulatory agencies may not approve the LDV/SOF fixed-dose combination in the currently anticipated timelines or at all, and that any marketing approvals, if granted, may have significant limitations on its use. Further, additional clinical studies of LDV/SOF, including subsequent results from ELECTRON2, may produce unfavorable results. As a result, Gilead may not be able to successfully commercialize LDV/SOF, and may make a strategic decision to discontinue its development if, for example, the market for the product fails to materialize as expected. Additional risks include the possibility of unfavorable results from additional studies of SOF/GS-5816 and the possibility that Gilead may make a strategic decision to discontinue development of the fixed-dose combination of SOF/GS-5816 if, for example, Gilead 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 Annual Report on Form 10-K for the year ended December 31, 2013, 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.

U.S. full prescribing information for Sovaldi is available at www.gilead.com.

Sovaldi is a registered trademark of Gilead Sciences, Inc.

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.

Source: Gilead Sciences, Inc.

Gilead Sciences, Inc.
Patrick O’Brien, +1 650-522-1936 (Investors)
Cara Miller, +1 650-522-1616 (Media (U.S.))
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