January 11, 2017

European Commission Grants Marketing Authorization for Gilead’s Vemlidy® (Tenofovir Alafenamide, TAF) for the Treatment of Chronic Hepatitis B Virus Infection

--Vemlidy® is the First New Treatment for Chronic Hepatitis B Infection to be Approved in the European Union in Nearly a Decade --

FOSTER CITY, Calif.--(BUSINESS WIRE)--Jan. 11, 2017-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the European Commission has granted marketing authorization for Vemlidy® (tenofovir alafenamide, TAF) 25 mg, a once-daily tablet for the treatment of chronic hepatitis B virus (HBV) infection in adults and adolescents (aged 12 years and older with body weight at least 35 kg).

The marketing authorization allows for the marketing of TAF in the 28 countries of the European Union, Norway and Iceland.

“As the first new treatment for chronic hepatitis B to be approved in Europe in nearly a decade, this approval marks a step forward in the management of a progressive, life-threatening disease affecting 13 million Europeans,” said Professor Pietro Lampertico, Head of the Gastroenterology and Hepatology Division at the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Italy. “Treating a lifelong disease such as chronic hepatitis B can present challenges as patients age, and the improvements in bone and renal laboratory safety parameters demonstrated by TAF compared to TDF allow it to provide an important new option for patients.”

TAF is a novel, targeted prodrug of tenofovir that has demonstrated antiviral efficacy similar to Gilead’s Viread® (tenofovir disoproxil fumarate, TDF) 245 mg, but at one-tenth the dose. Data show that because TAF has greater plasma stability and more efficiently delivers tenofovir to hepatocytes (cells of the liver) compared to TDF, it can be given at a lower dose, which means there is less tenofovir in the bloodstream. By reducing exposure to tenofovir, TAF is associated with improved renal and bone laboratory safety parameters compared to TDF in clinical trials.

“TAF reflects Gilead’s ongoing commitment to improve and simplify care for people with chronic infectious diseases, including hepatitis B, while we continue our research efforts for curative treatments,” said Norbert Bischofberger, PhD, Executive Vice President, Research and Development and Chief Scientific Officer, Gilead Sciences. “We look forward to making TAF available as quickly as possible throughout the European Union.”

TAF’s approval is supported by 48-week data from two international Phase 3 studies (Studies 108 and 110) in 1,298 adult chronic HBV patients. Study 108 randomized 425 HBeAg-negative patients to receive either TAF or TDF, and Study 110 randomized 873 HBeAg-positive patients to receive either TAF or TDF. Both studies met their primary endpoint of non-inferiority to TDF based on the percentage of patients with chronic hepatitis B with plasma HBV DNA levels below 29 IU/mL at 48 weeks of therapy. Patients in the TAF arm of the trials also experienced numerically higher rates of normalization of blood serum alanine aminotransferase (ALT) levels. Both studies showed TAF and TDF to be well-tolerated by patients and discontinuations due to adverse events were 1% and 1.2%, respectively. The most common reported adverse events with TAF were diarrhea, vomiting, nausea, abdominal pain, abdominal distension, flatulence, fatigue, headache, dizziness, rash, pruritus, increased ALT and arthralgia.

While the primary efficacy assessment was performed at week 48, data show that at week 72 viral suppression as well as biochemical responses were maintained with continued TAF treatment. The safety assessment includes analyses performed at both week 48 and week 72 of treatment (median duration of exposure of 88 weeks), and safety endpoints included changes from baseline in bone mineral density at the hip and spine, and changes from baseline in serum creatinine and in eGFR, key indicators of renal health. In both studies, at weeks 48 and 72, changes in renal and bone laboratory safety parameters favored the TAF treatment groups.

Vemlidy was approved by the U.S. Food and Drug Administration on November 10, 2016 for the treatment of chronic HBV infection in adults with compensated liver disease, and by the Japanese Ministry of Health, Labour and Welfare on December 19, 2016 for the suppression of viral replication in chronic hepatitis B patients with evidence of hepatitis B virus replication and abnormal liver function.

For important safety information for TAF in Europe, including posology and method of administration, special warnings, drug interactions and adverse drug reactions, please see the European Summary of Product Characteristics (SmPC) for Vemlidy, available from the EMA website at http://www.ema.europa.eu. The full prescribing information for TAF in the United States, including BOXED WARNING, is available at www.gilead.com.

Important Safety Information and Indication for Vemlidy in the U.S.

BOXED WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT SEVERE ACUTE EXACERBATION OF HEPATITIS B

  • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs.
  • Discontinuation of anti-hepatitis B therapy, including VEMLIDY, may result in severe acute exacerbations of hepatitis B. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy, including VEMLIDY. If appropriate, resumption of anti-hepatitis B therapy may be warranted.

Warnings and Precautions

  • Risk of Development of HIV-1 Resistance in HBV/HIV-1 Coinfected Patients: Due to this risk, VEMLIDY alone is not recommended for the treatment of HIV-1 infection. Safety and efficacy of VEMLIDY have not been established in HBV/HIV-1 coinfected patients. HIV antibody testing should be offered to all HBV-infected patients before initiating therapy with VEMLIDY, and, if positive, an appropriate antiretroviral combination regimen that is recommended for HBV/HIV-1 coinfected patients should be used.
  • New Onset or Worsening Renal Impairment: Cases of acute renal failure and Fanconi syndrome have been reported with the use of tenofovir prodrugs. In clinical trials of VEMLIDY, there have been no cases of Fanconi syndrome or proximal renal tubulopathy (PRT). Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue VEMLIDY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome.Renal monitoring: Assess serum creatinine, serum phosphorus, CrCl, urine glucose, and urine protein prior to initiating and during therapy in all patients as clinically appropriate.

Adverse Reactions

Most common adverse reactions (incidence ≥5%; all grades) were headache, abdominal pain, fatigue, cough, nausea and back pain.

Drug Interactions

  • Coadministration of VEMLIDY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of tenofovir and the risk of adverse reactions.
  • Coadministration of VEMLIDY is not recommended with the following: oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, or St. John’s wort. Such coadministration is expected to decrease the concentration of tenofovir alafenamide, reducing the therapeutic effect of VEMLIDY. Drugs that strongly affect P-gp and BCRP activity may lead to changes in VEMLIDY absorption.

Consult the full prescribing information for VEMLIDY for more information on potentially significant drug interactions, including clinical comments.

Dosage and Administration

  • Dosage: Adults; 1 tablet taken once daily with food.
  • Renal Impairment: Not recommended in patients with CrCl
  • Hepatic Impairment: Not recommended in patients with decompensated (Child-Pugh B or C) hepatic impairment.
  • Testing prior to initiation: HIV infection.

Indication

VEMLIDY is indicated for the treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease.

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. 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 risk that physicians may not see the benefits of prescribing Vemlidy. 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, 2016, 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.

The European SmPCs for Vemlidy and Viread are available from the EMA website at www.ema.europa.eu.

Vemlidy and Viread 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 or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000

Source: Gilead Sciences, Inc.

Gilead Sciences, Inc.InvestorsSung Lee, +1 650-524-7792orMedia (U.S.)Kelsey Grossman, +1 650-378-2103

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