-- Additional Presentations Highlight Early
Research of Investigational Agents For HBV Cure --
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.
Vemlidy
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 http://anzctr.org.au/.
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
BOXED WARNING: POST TREATMENT SEVERE ACUTE EXACERBATION OF
HEPATITIS B
- 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.
- 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 mL/min.
- 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
www.gilead.com.
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, follow Gilead on
Twitter (@GileadSciences) or call Gilead Public Affairs at
1-800-GILEAD-5 or 1-650-574-3000.
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Gilead Sciences, Inc.Sung Lee, 650-524-7792 (Investors)Kelsey
Grossman, 650-378-2103 (Media)
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