– Data Demonstrate Sofosbuvir-Based Regimens
Achieve High Cure Rates in Hepatitis C Patient Populations with
Unmet Need –
– Early Data from Gilead’s Functional
Hepatitis B Cure Program Suggest Activation of Immune Cells Crucial
to Viral Clearance –
Gilead Sciences, Inc. (Nasdaq: GILD) today announced results
from studies investigating Epclusa® (sofosbuvir 400mg/velpatasvir
100mg) in chronic hepatitis C virus (HCV) infected patients with
severe renal impairment undergoing dialysis and Harvoni®
(ledipasvir/sofosbuvir) in pediatric HCV patients aged three to
five years, adding to the efficacy and safety profile of
sofosbuvir-based regimens across diverse patient populations. These
results, along with data from Gilead’s hepatitis B virus (HBV) cure
development program, are being presented at The Liver Meeting® 2018
in San Francisco this week.
“Our scientific leadership has helped transform the treatment of
patients with chronic hepatitis C infection and we remain committed
to ensuring effective and well-tolerated treatment options for a
broad range of patient populations.” said John McHutchison, AO, MD,
Chief Scientific Officer, Head of Research and Development, Gilead
Sciences. “For patients with chronic hepatitis B infection, we are
intensifying our efforts to advance research and development toward
a functional cure.”
Further Progress in the Treatment of
Hepatitis C
Results from an open-label Phase 2 study demonstrated that
treatment with the once-daily single-tablet regimen of Epclusa for
12 weeks in patients with genotype 1, 2, 3, 4 or 6 HCV and severe
renal impairment undergoing dialysis resulted in cure rates (SVR12,
or undetectable viral load 12 weeks after completion of therapy) of
95 percent (n=56/59) with only two patients experiencing virologic
failure. The most common adverse events (AEs) (>10 percent) were
headache, fatigue, nausea, vomiting and insomnia. No patients
discontinued therapy due to an adverse event.
In another open-label Phase 2 study, children aged three to five
years old with genotype 1 or 4 HCV infection received weight-based
oral dosing of ledipasvir/sofosbuvir granules 33.75 mg/150 mg if
< 17 kg or 45 mg/ 200 mg if ≥ 17 kg) once-daily for 12 weeks.
Overall, 97 percent (n=33/34) of the patients were cured, and none
experienced virologic failure. The most common AEs (>10 percent)
were vomiting, cough, pyrexia, rhinorrhea and streptococcal
pharyngitis. One patient discontinued treatment due to an adverse
event of abnormal drug taste.
The use of Epclusa and Harvoni, including granules formulation,
in the aforementioned patient populations is investigational; their
safety and efficacy have not been established. The granule
formulation is not approved. Epclusa and Harvoni are both indicated
in the US for the treatment of chronic HCV infection in patients
with no cirrhosis or compensated cirrhosis: Epclusa for adults with
genotypes 1-6; and Harvoni for patients 12 years and older (or ≥35
kg) with genotypes 1, 4, 5 and 6. The US product labels for Epclusa
and Harvoni each contain a Boxed Warning for the risk of hepatitis
B reactivation in HCV/HBV co-infected patients. See below for US
Important Safety Information.
Hepatitis B Cure
Research
Gilead is presenting data on GS-9688, an investigational, oral
selective toll-like receptor 8 (TLR8) agonist, one of several
compounds under investigation as part of Gilead’s HBV cure program.
The data support continued development of GS-9688 as a potential
therapeutic approach for achieving a functional cure for patients
with chronic HBV infection.
In the first-in-human, healthy volunteer safety study, GS-9688
was well-tolerated at single ascending doses up to 5mg and resulted
in pharmacodynamic activity as demonstrated by the production of
the systemic cytokines IL-1RA and IL-12p40 and by the activation of
key relevant immune cells including natural killer (NK) cells and
mucosal-associated invariant T (MAIT) cells. The most commonly
reported AEs among people receiving doses up to and including 5 mg
were nausea and vomiting. There were no reports of Grade 3 or
higher AEs, laboratory AEs or serious adverse events (SAEs) and no
discontinuations or deaths.
In a Phase 1b safety and tolerability study of GS-9688 in HBV
chronically infected patients, dose-dependent activation of the
cytokines IL-12p40 and IL-1RA was demonstrated with once weekly
dosing for up to 4 weeks in viremic and virally-suppressed
patients. There were no reports of SAEs; the most common AEs were
headache and nausea. Based on these data, GS-9688 is currently
being evaluated in Phase 2 studies in patients with chronic
hepatitis B.
GS-9688 is an investigational agent and not approved; its safety
and efficacy have not been established.
Latest Research in Hepatitis B
Treatment
Presentations on Vemlidy® (tenofovir alafenamide 25mg, TAF) add
further evidence to its established safety and efficacy profile in
adults with chronic HBV and compensated liver disease, including
longer term data on the safety of Vemlidy in virologically
suppressed HBV patients. Through three years of treatment, patients
originally randomized to receive TAF continued to show an improved
bone and renal safety profile compared to treatment with tenofovir
disoproxil fumarate 300mg (TDF) with maintained viral suppression.
In a separate study in post-liver transplant patients virally
suppressed on TDF-based regimens, switching to TAF maintained viral
suppression in all TAF-treated patients with improvements in renal
function and bone mineral density, after 48 weeks of treatment.
The use of Vemlidy in post-liver transplant patients is
investigational; its safety and efficacy have not been established.
Vemlidy is indicated in the US for the treatment of chronic HBV
infection in adults with compensated liver disease. The US
Prescribing Information for VEMLIDY contains a Boxed Warning
regarding the risk of post treatment severe acute exacerbation of
hepatitis B; see below for Important Safety Information.
US Important Safety Information About
Epclusa and Harvoni
BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN
HCV/HBV COINFECTED PATIENTS
Test all patients for evidence of current or prior hepatitis
B virus (HBV) infection before initiating treatment with EPCLUSA or
HARVONI. HBV reactivation has been reported in HCV/HBV coinfected
patients who were undergoing or had completed treatment with HCV
direct acting antivirals (DAAs) and were not receiving HBV
antiviral therapy. Some cases have resulted in fulminant hepatitis,
hepatic failure, and death. Cases have been reported in patients
who are HBsAg positive, in patients with serologic evidence of
resolved HBV, and also in patients receiving certain
immunosuppressant or chemotherapeutic agents; the risk of HBV
reactivation associated with treatment with HCV DAAs may be
increased in patients taking these other agents. Monitor HCV/HBV
coinfected patients for hepatitis flare or HBV reactivation during
HCV treatment and post-treatment follow-up. Initiate appropriate
patient management for HBV infection as clinically
indicated.
Warnings and Precautions
Serious Symptomatic Bradycardia When Coadministered with
Amiodarone: Amiodarone is not recommended for use with EPCLUSA
or HARVONI 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. A fatal cardiac
arrest was reported in a patient taking amiodarone who was
coadministered a sofosbuvir containing regimen. 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.
Risk of Reduced Therapeutic Effect Due to Use with P-gp
Inducers and/or Moderate to Potent Inducers of CYP: Rifampin,
St. John’s wort and carbamazepine are not recommended for use with
EPCLUSA or with HARVONI. P-gp inducers may significantly decrease
ledipasvir, sofosbuvir and/or velpatasvir plasma concentrations.
Moderate to potent inducers of CYP2B6, CYP2C8 or CYP3A4 may
significantly decrease sofosbuvir and/or velpatasvir plasma
concentrations.
Adverse Reactions
The most common adverse reactions (≥10%, all grades) with
EPCLUSA were headache and fatigue.
The most common adverse reactions (≥10%, all grades) with
HARVONI were fatigue, headache, and asthenia.
Drug Interactions
EPCLUSA: Coadministration is not recommended with
topotecan due to increased concentrations of topotecan; or with
proton-pump inhibitors, oxcarbazepine, phenobarbital, phenytoin,
rifabutin, rifapentine, efavirenz, and tipranavir/ritonavir due to
decreased concentrations of sofosbuvir and/or velpatasvir.
HARVONI: Coadministration is not recommended with
oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine,
and tipranavir/ritonavir due to decreased concentrations of
ledipasvir and sofosbuvir; or with co-formulated
elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate
due to increased concentrations of tenofovir; or with simeprevir
due to increased concentrations of ledipasvir and simeprevir; or
with rosuvastatin due to increased concentrations of
rosuvastatin.
Consult the full Prescribing Information for EPCLUSA and HARVONI
for more information on potentially significant drug interactions,
including clinical comments.
US Important Safety Information About
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 should not
be used 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. Monitor renal function in all
patients – See Dosage and Administration.
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, cough, back pain, fatigue, nausea,
arthralgia, diarrhea, and dyspepsia.
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-glycoprotein (P-gp) and breast cancer resistance protein
(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, Screening, and Monitoring: VEMLIDY is
not recommended in patients with CrCl <15 mL/min. In all
patients, assess serum creatinine, estimated creatinine clearance,
urine glucose, and urine protein prior to initiating and during
treatment, on a clinically appropriate schedule. In patients with
chronic kidney disease, also assess serum phosphorus.
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, Inc. is a research-based biopharmaceutical
company that discovers, develops and commercializes innovative
medicines in areas of unmet medical need. The company strives to
transform and simplify care for people with life-threatening
illnesses around the world. Gilead has operations in more than 35
countries worldwide, with headquarters in Foster City, California.
For more information on Gilead Sciences, please visit the company's
website at www.gilead.com
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 Gilead’s ability to complete its Phase 2 clinical trial
program evaluating GS-9688 in the currently anticipated timeline or
at all. In addition, there is the possibility of unfavorable
results from ongoing and additional clinical trials involving
Epclusa, Harvoni, Vemlidy and GS-9688. Further, it is possible that
Gilead may make a strategic decision to discontinue development of
GS-9688, and as a result, this compound may never be successfully
commercialized. 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, 2018, 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 Epclusa,
Harvoni and Vemlidy, including BOXED WARNINGS, is available
at www.gilead.com.
Epclusa, Harvoni and Vemlidy 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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