Market Overview

Gilead Presents Data at the International Liver Congress™ 2017 Supporting the Efficacy and Safety of Vemlidy in Patients with Chronic Hepatitis B After 96 Weeks, and Also After Switching From Viread


Gilead Sciences, Inc. (NASDAQ:GILD) today announced 96-week results
from two ongoing Phase 3 studies evaluating the safety and efficacy of
daily Vemlidy® (tenofovir alafenamide, TAF 25mg) in immune
active patients and in patients switching from Gilead's Viread®
(tenofovir disoproxil fumarate, TDF 300mg). Vemlidy is a once-daily
treatment approved for adults with chronic hepatitis B virus (HBV)
infection with compensated liver disease. In addition, Gilead presented
data from preclinical studies of investigational compounds being studied
for their potential role in HBV cure strategies. Data are being
presented this week at The International Liver Congress 2017
in Amsterdam.

Vemlidy is a novel, targeted prodrug of tenofovir that has demonstrated
antiviral efficacy that is noninferior to that of Viread at Week 48 in
patients with chronic HBV. Vemlidy treatment at the same time point also
demonstrated a beneficial impact on renal and bone laboratory safety
parameters compared to Viread. Analyses now conducted at Week 96 of
treatment demonstrate continued benefits of Vemlidy including high rates
of viral suppression, with no evidence of resistance, and less impact on
renal and bone safety parameters as compared to Viread (#PS-042,
#FRI-153). Additionally, patients switching from Viread to Vemlidy after
Week 96 demonstrated maintenance of viral suppression, improvement in
serum alanine aminotransferase (ALT) normalization rates, and
improvement in bone and renal parameters 24 weeks after switching to
Vemlidy (#PS-041: "Hepatitis B and D: emerging treatment options").

"The results observed in these studies reinforce Vemlidy as an important
treatment option for patients living with chronic HBV infection," said
Norbert Bischofberger, PhD, Executive Vice President of Research and
Development and Chief Scientific Officer at Gilead. "Additionally, the
preclinical data presented at this EASL meeting illustrate our
scientific approach to evaluating compounds with distinct mechanisms of
action aimed at curing HBV infection."

Vemlidy has a boxed warning in its U.S. product label regarding the risk
of post-treatment severe acute exacerbation of hepatitis B. See below
for important safety information.


The two randomized, double-blinded Phase 3 studies (Studies 108 and 110)
from which the data are presented evaluated the use of Vemlidy given
once-daily versus Gilead's Viread given once-daily in treatment-naïve
and treatment-experienced adults with HBeAg-negative and HBeAg-positive
chronic HBV infection.

Results demonstrate continued advantages of treatment with Vemlidy over
Viread between Week 48 and Week 96. Virologic response rates at Week 96
were 90 percent (n=257/285) and 91 percent (n=127/140) in HBeAg-negative
patients (Study 108) receiving Vemlidy and Viread, respectively. In
HBeAg-positive patients (Study 110), virologic response rates at Week 96
were 73 percent (n=423/581) and 75 percent (n=218/292) in the Vemlidy
and Viread groups, respectively. In both studies, a greater percentage
of patients taking Vemlidy achieved normalization of ALT levels relative
to patients taking Viread as measured by both central laboratory
criteria, and by the American Association for the Study of Liver
Diseases (AASLD) criteria. Patients receiving Vemlidy also demonstrated
ongoing benefits at Week 96 in bone and renal safety parameters,
including smaller declines from baseline in hip and spine bone mineral
density (BMD) and smaller declines from baseline in estimated creatinine
clearance compared with patients taking Viread in both studies. Similar
rates of adverse events and low and similar rates of adverse events
leading to discontinuation were observed in both treatment arms. Viral
resistance analyses showed no resistance to Vemlidy or Viread at Week 96.

A post-hoc analysis evaluated a subset of 541 patients from Studies 108
and 110 who completed 96 weeks of treatment with double-blind Vemlidy or
Viread and were then switched to open-label treatment with Vemlidy.
Among patients switched from Viread to Vemlidy at Week 96 (n=180),
virologic suppression was maintained and the rates of ALT normalization
by central laboratory criteria and AASLD criteria significantly
increased during the subsequent 24 weeks of Vemlidy therapy. These
patients also demonstrated further improvements in hip and spine BMD and
had significant improvements in estimated creatinine clearance.
Longer-term data are required to confirm the benefits of switching from
Viread to Vemlidy for the treatment of chronic HBV.

Hepatitis B Pipeline

In addition, Gilead has several ongoing research programs with the goal
of achieving functional cure for HBV-infected patients. Preclinical data
with some of Gilead's novel investigational compounds are being
presented at the Congress.

GS-5801 is an oral liver-targeted prodrug of a small molecule inhibitor
of KDM5, a histone lysine demethylase. Results from in vitro preclinical
studies (#SAT-160) demonstrated activity of GS-5801 in HBV-infected
primary human hepatocytes with significant declines in viral proteins
and HBV RNA. In addition, in vivo data (#THU-171) demonstrated
the pharmacodynamic response of GS-5801 within the liver, in animal
models. GS-5801 is currently being evaluated in Phase 1 trials in
healthy subjects and in patients with chronic HBV infection.

GS-9688, an oral selective toll-like receptor 8 (TLR8) agonist,
demonstrated in vitro and in vivo pharmacodynamic effects
consistent with selective TLR8 activation, including the production of
antiviral cytokines (#SAT-168). Further, in an efficacy animal model of
chronic HBV infection, GS-9688 treatment demonstrated a sustained
antiviral response in chronically infected woodchucks (#SAT-165).
GS-9688 is currently being evaluated in Phase 1 trials in healthy
subjects and in patients with chronic HBV infection.

Further information about the clinical studies described above can be
found at

GS-5801 and GS-9688 are investigational products and have not been
determined to be safe or efficacious.

U.S. Important Safety Information for Vemlidy


  • 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
    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
    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.
  • Lactic Acidosis and Severe Hepatomegaly with Steatosis: Fatal
    cases have been reported with the use of nucleoside analogs, including
    tenofovir DF. Discontinue Vemlidy if clinical or laboratory findings
    suggestive of lactic acidosis or pronounced hepatotoxicity develop,
    including hepatomegaly and steatosis in the absence of marked
    transaminase elevations.

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 <15
  • Hepatic Impairment: Not recommended in patients with
    decompensated (Child-Pugh B or C) hepatic impairment.
  • Testing prior to initiation: HIV infection.

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. 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 for the
treatment of HBV. In addition, Gilead may be unable to achieve a
functional cure for HBV with any of its product candidates, including
GS-5801 and GS-9688. 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 quarter ended
December 31, 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.

U.S. full Prescribing Information including BOXED WARNING for
Vemlidy is available at

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,
follow Gilead on Twitter (
or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

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