– Full Results from Four Phase 3 ASTRAL Studies of Sofosbuvir/Velpatasvir to be Presented —
San Francisco, November 14, 2015 – Gilead Sciences, Inc. (Nasdaq: GILD) today announced it will present 32 scientific presentations related to its approved medicines and investigational therapies for the treatment of chronic hepatitis C virus (HCV) infection at The Liver Meeting 2015 in San Francisco. Data include results from studies of Harvoni® (ledipasvir/sofosbuvir) and Sovaldi® (sofosbuvir) that advance the understanding of the profiles of these drugs in several patient populations. Detailed results from the four Phase 3 ASTRAL studies evaluating the company’s next potential single tablet regimen – a once-daily combination of velpatasvir (VEL), an investigational pan-genotypic NS5A inhibitor, with sofosbuvir (SOF) also will be presented.
“We continue to advance our understanding of the safety and efficacy of sofosbuvir and ledipasvir/sofosbuvir in diverse groups of HCV patients, including several special patient populations that historically have not been studied,” said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer at Gilead. “We are also pleased to share data evaluating our next-generation investigational sofosbuvir-based therapies SOF/VEL, and SOF/VEL plus GS-9857. In total, the HCV data highlighted this week demonstrate the strengths of sofosbuvir as the backbone of multiple hepatitis C treatment regimens in numerous hepatitis C-infected patient populations.”
Ledipasvir/sofosbuvir
LDV/SOF is the first single-tablet regimen for the treatment of chronic HCV genotype 1. Following the U.S. Food and Drug Administration’s (FDA) approval of Gilead’s supplemental new drug application on November 12, LDV/SOF is now also indicated for genotypes 4, 5 and 6 in the US. In Europe LDV/SOF is indicated for the treatment of chronic hepatitis C in adults with genotypes 1, 3 and 4.
Data presented this week demonstrate the efficacy and safety profile of LDV/SOF in populations with unmet medical needs including pre- and post-liver transplant patients with decompensated cirrhosis (Posters #11301, #10452, #10493). In addition, Oral #964 describes a review of safety data from the SOLAR-1 and SOLAR-2 studies that suggest a new algorithm for the detection of potential drug induced liver injury in patients with decompensated cirrhosis receiving DAA-based regimens. A new analysis and an additional study describe the efficacy and safety of LDV/SOF in Asian patients (Poster #11055) and in patients with hereditary bleeding disorders (Poster #10346).
Sofosbuvir
Results and new analyses from several studies highlighting the utility of sofosbuvir in combination with other agents in several diverse and newly-studied populations, including Asian patients (Poster #10807) and those with severe renal impairment (Poster #11288) also will be presented this week. Sofosbuvir is approved in combination with other agents for the treatment of genotypes 1-4 chronic HCV infection in the US and for genotypes 1-6 in Europe. No dose adjustment of sofosbuvir is required for patients with mild or moderate renal impairment. The safety and appropriate dose of sofosbuvir have not been established in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2) or end stage renal disease (ESRD) requiring haemodialysis.9
Hepatitis C Pipeline
Detailed results from Gilead’s four Phase 3 ASTRAL studies of SOF/VEL in patients with genotype 1-6 chronic HCV infection ASTRAL-1 (Oral LB-210), ASTRAL-2 (Oral #20511), ASTRAL-3 (Oral #24912) and ASTRAL-4 (Poster LB-1313) will be presented at various times throughout The Liver Meeting 2015. Based on these data, Gilead submitted a new drug application (NDA) for SOF/VEL to the FDA on October 28, 2015. The company plans to submit a regulatory application for approval of SOF/VEL in the European Union by the end of the year. If approved, SOF/VEL would be Gilead’s third HCV medication and the first all-oral, pan-genotypic single-tablet HCV regimen.
Gilead will also present new data from a study evaluating the safety and efficacy of the combination of SOF/VEL with GS-9857, an investigational pangenotypic NS3/4A protease inhibitor, in patients with HCV genotype 1 and 3 infection (Oral #3814). Based on these data, SOF, VEL and GS-9857 co-formulated into a fixed-dose combination will be advanced into Phase 3 studies.
Abstracts for Gilead’s presentations can be accessed at
http://www.aasld.org/sites/default/files/2015SupplementFULLTEXT.pdf. Further information about the clinical studies described above can be found at www.clinicaltrials.gov.
Uses in certain HCV patient populations highlighted above for LDV/SOF and sofosbuvir are investigational and their safety and efficacy profile have not yet been determined. SOF/VEL and SOF/VEL/GS-9857 are investigational products and their tolerability and efficacy profiles are yet to be determined.
Important Safety Information About LDV/SOF
The summary of product characteristics of co-prescribed medicinal products should be consulted before starting therapy with LDV/SOF.
Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone:Amiodarone is not recommended for use with LDV/SOF due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
LDV/SOF should not be administered concomitantly with other medicinal products containing sofosbuvir.
In clinical studies, fatigue and headache were more common in patients treated with LDV/SOF compared to placebo.
Contraindications include hypersensitivity to the active substances or to any of the excipients. Coadministration with rosuvastatin or St. John’s wort (Hypericum perforatum) is contraindicated. Coadministration with certain P-glycoprotein (P-gp) inducers (e.g. rifampicin, carbamazepine and phenytoin) is not recommended. Monitoring of digoxin and dabigatran is recommended when used with LDV/SOF. Caution and frequent renal monitoring is recommended for co-administration with certain HIV antiretroviral regimens. Safety has not been established in patients with severe renal impairment. For patients on statins dose reduction should be considered and careful monitoring for statin adverse events (myopathy and rhabdomyolysis) should be undertaken.
A Summary of Product Characteristics is available at www.ema.europa.eu.
Important Safety Information About Sofosbuvir
Warnings and Precautions
Serious Symptomatic Bradycardia When Coadministered with Amiodarone and Another HCV Direct Acting Antiviral (DAA): Amiodarone is not recommended for use with sofosbuvir in combination with another DAA due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
Important Safety Information
Contraindications: Hypersensitivity to the active substance or to any of the excipients.
Special warnings and precautions for use: The summary of product characteristics of co-prescribed medicinal products should be consulted before starting therapy with sofosbuvir. When sofosbuvir is used in combination with ribavirin (RBV) or pegylated interferon (PEG-IFN)/RBV, women of childbearing potential or their male partners must use an effective form of contraception during the treatment and for a period of time after the treatment as recommended in the Summary of Product Characteristics for RBV. Refer to the Summary of Product Characteristics for RBV for additional information.
Use with potent P-gp inducers: Medicinal products that are potent P-glycoprotein (P-gp) inducers in the intestine (e.g. rifampicin, St. John’s wort [Hypericum perforatum], carbamazepine and phenytoin) may significantly decrease sofosbuvir plasma concentration leading to reduced therapeutic effect of sofosbuvir. Such medicinal products should not be used with sofosbuvir.
For the Summary of Product Characteristics please visit www.ema.europa.eu.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercialises innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.
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 these studies and other ongoing and subsequent clinical trials involving Harvoni, Sovaldi, SOF/VEL and SOF/VEL with GS-9857. The FDA may not approve the SOF/VEL fixed-dose combination, and any marketing approvals, if granted, may have significant limitations on its use. In addition, Gilead may be unable to file for regulatory approval of SOF/VEL in other geographies in the currently anticipated timelines. As a result, Gilead may not be able to successfully commercialize SOF/VEL. 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, 2015, 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.
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EU full prescribing information for Sovaldi and Harvoni is available at www.ema.europa.eu
Sovaldi and Harvoni are registered trademarks of Gilead Sciences, Inc. or its related companies.
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.
References
1. Welzel, TM, et al. On-treatment HCV RNA Decline in Pre-and Post-Liver Transplant Patients with Different Degrees of Fibrosis and Cirrhosis: a combined analysis of the SOLAR trials. Poster session presented at the Liver Meeting of the American Association for the Study of Liver Diseases; 2015 Nov 13-17; San Francisco, CA.
2. Welzel, TM, et al. Effect of Different Immunosuppressant Regimens on Viral Kinetics and SVR12 in Liver Transplant Recipients Treated with LDV/SOF in the SOLAR Trials. Poster session presented at the Liver Meeting of the American Association for the Study of Liver Diseases; 2015 Nov 13-17; San Francisco, CA.
3. Gane, EJ, et al. High efficacy of ledipasvir/sofosbuvir with ribavirin in patients with decompensated cirrhosis or liver transplantation and HCV infection: combined efficacy from the SOLAR-1 and SOLAR-2 trials. Poster session presented at the Liver Meeting of the American Association for the Study of Liver Diseases; 2015 Nov 13-17; San Francisco, CA.
4. Muir, AJ, et al. Detecting Drug-Induced Liver Injury in Patients with Decompensated Chronic Hepatitis C: A Review of the SOLAR-1 and SOLAR-2 Studies. Oral session presented at the Liver Meeting of the American Association for the Study of Liver Diseases; 2015 Nov 13-17; San Francisco, CA.
5. Mizokami, M, et al. Asian Patients with Genotype 1 HCV Infection Achieve 99% Sustained Virologic Response with 12 Weeks of Ledipasvir/Sofosbuvir Single Tablet Regimen: Integrated analysis of Phase 3 Multicenter Studies. Poster session presented at the Liver Meeting of the American Association for the Study of Liver Diseases; 2015 Nov 13-17; San Francisco, CA.
6. Walsh, C, et al. Approved All-oral Sofosbuvir Regimens are Safe and Highly Effective in Patients with Hereditary Bleeding Disorders. Poster session presented at the Liver Meeting of the American Association for the Study of Liver Diseases; 2015 Nov 13-17; San Francisco, CA.
7. Omata, M, et al. Asian Patients with Chronic Genotype 2 HCV Infection Achieve 98% Sustained Virologic Response Following 12 Week administration of Sofosbuvir in Combination with Ribavirin: Integrated analysis of Phase 3 Multicenter Studies. Poster session presented at the Liver Meeting of the American Association for the Study of Liver Diseases; 2015 Nov 13-17; San Francisco, CA.
8. Martin, P, et al. Safety and Efficacy of Treatment with Daily Sofosbuvir 400 mg + Ribavirin 200 mg for 24 Weeks in Genotype 1 or 3 HCV-Infected Patients with Severe Renal Impairment. Poster session presented at the Liver Meeting of the American Association for the Study of Liver Diseases; 2015 Nov 13-17; San Francisco, CA.
9. Harvoni, Summary of Product Characteristics. Accessed November 2015. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR__Product_Information/human/003850/WC500177995.pdf
10. Feld, JJ, et al. Phase 3 Double-Blind Placebo-Controlled Evaluation of Sofosbuvir/Velpatasvir Fixed Dose Combination for 12 Weeks in Naïve and Experienced Genotype 1, 2, 4, 5, 6 HCV Infected Patients with and without cirrhosis: Results of the ASTRAL-1 Study. Poster session presented at the Liver Meeting of the American Association for the Study of Liver Diseases; 2015 Nov 13-17; San Francisco, CA.
11. Sulkowski, MS, et al. A Randomized Controlled Trial of Sofosbuvir/GS-5816 Fixed Dose Combination for 12 Weeks Compared to Sofosbuvir with Ribavirin for 12 Weeks in Genotype 2 HCV Infected Patients: The Phase 3 ASTRAL-2 Study. Oral session presented at the Liver Meeting of the American Association for the Study of Liver Diseases; 2015 Nov 13-17; San Francisco, CA
12. Mangia, A, et al. Sofosbuvir/GS-5816 Fixed Dose Combination for 12 Weeks Compared to Sofosbuvir with Ribavirin for 24 Weeks in Genotype 3 HCV Infected Patients: The Randomized Controlled Phase 3 ASTRAL-3 Study. Oral session presented at the Liver Meeting of the American Association for the Study of Liver Diseases; 2015 Nov 13-17; San Francisco, CA.
13. Charlton, M, et al. Sofosbuvir/Velpatasvir Fixed Dose Combination For The Treatment Of HCV In Patients With Decompensated liver Disease: The Phase 3 ASTRAL-4 Study. Poster session presented at the Liver Meeting of the American Association for the Study of Liver Diseases; 2015 Nov 13-17; San Francisco, CA.
14. Gane, EJ, et al. Sofosbuvir/GS-5816+GS-9857 for 6 or 8 Weeks in Genotype 1 or 3 HCV-infected Patients. Oral session presented at the Liver Meeting of the American Association for the Study of Liver Diseases; 2015 Nov 13-17; San Francisco, CA.
