-- High Cure Rates in More Than 600 Genotype
1 and 4 Patients With Limited or No Approved Treatment Options
--
Gilead Sciences, Inc. (Nasdaq: GILD) today announced results
from several Phase 2 clinical studies evaluating investigational
uses of Harvoni® (ledipasvir 90 mg/sofosbuvir 400 mg) and other
Sovaldi® (sofosbuvir 400 mg)-based regimens for the treatment of
chronic hepatitis C virus (HCV) infection in patients with advanced
liver disease, including patients with decompensated cirrhosis,
patients with fibrosing cholestatic hepatitis C (a rare and severe
form of the disease following liver transplantation) and patients
with portal hypertension. These data will be presented this week at
the 50th Annual Meeting of the European Association for the Study
of the Liver (The International Liver Congress™ 2015) in Vienna,
Austria.
“The patients included in these analyses are among the most
difficult to both treat and cure and, until now, have had limited
or no treatment options,” said Michael P. Manns, MD, Professor and
Chairman, Department of Gastroenterology, Hepatology and
Endocrinology, Hannover Medical School, Hannover, Germany. “These
data demonstrate that, even among these difficult-to-treat patient
groups, sofosbuvir-based oral therapy offers the potential of high
cure rates, improves outcomes and is generally well tolerated with
a favorable safety profile.”
Harvoni and Sovaldi are each approved in the United States for
the treatment of chronic HCV infection. Harvoni is indicated for
patients with genotype 1; Sovaldi is used in combination with other
agents and its efficacy has been established in patients with
genotypes 1-4.
Decompensated and Post-Liver
Transplantation
In SOLAR-2 (Study GS-US-337-0124, Oral #G02), 328 genotype 1 or
4 HCV patients with decompensated liver disease before liver
transplantation or recurrent HCV infection following liver
transplantation were randomized to receive either 12 or 24 weeks of
Harvoni plus ribavirin (RBV). Ten patients were excluded from the
analysis because of transplantation (n=7) or because they were
pre-transplantation, but not decompensated (n=3); an additional 27
of these patients have not yet reached post-treatment week 12. The
number and proportion of genotype 1 patients with available data
achieving sustained virologic response 12 weeks after treatment
(SVR12) are summarized in the table below.
SVR12 Treatment Duration Pre-Transplant
Recurrent HCV Post-Liver Transplantation
DecompensatedCirrhosis(CPT B+C)
Non-Cirrhotic (F0-F3)and
CompensatedCirrhosis (CPT A)
DecompensatedCirrhosis(CPT B+C)
12 weeks 86% (n=37/43) 96% (n=72/75) 91% (n=20/22) 24 weeks 85%
(n=35/41) 98% (n=57/58) 95% (n=19/20)
Of the 32 genotype 4 patients, 27 (84 percent) achieved SVR12.
Additionally, among patients with compensated and decompensated
cirrhosis before and after liver transplantation, virologic
response was associated with improvements in Model for End-Stage
Liver Disease (MELD) and CPT scores used to stage end-stage liver
disease.
The most common adverse events were fatigue, anemia, nausea and
headache. Overall, six patients discontinued treatment due to
adverse events, five of whom had decompensated cirrhosis.
Further supporting the safety profile of Harvoni plus RBV among
this patient population was data from a pooled safety analysis of
659 patients treated in the SOLAR-1 and SOLAR-2 studies (ePoster
#P0774). Both studies evaluated Harvoni plus RBV for 12 or 24 weeks
in genotype 1 or 4 HCV patients with decompensated liver disease or
recurrent HCV infection following liver transplantation. SOLAR-1
was conducted in the United States, with data presented in November
at The Liver Meeting 2014 and SOLAR-2 was conducted in Australia,
Canada, Europe and New Zealand. Overall, adverse events were
similar to those seen in previous studies, including the Phase 3
ION studies. Fewer than three percent (n=19/659) of patients
discontinued due to an adverse event, none of which were attributed
to Harvoni treatment. There were a total of 20 deaths in these two
studies, none of which was assessed by the investigator as related
to study treatment.
Fibrosing Cholestatic Hepatitis
C
A further subset of the SOLAR-1 and SOLAR-2 studies (ePoster
#P0779) demonstrated 100 percent SVR12 rates among 11 patients who
were confirmed to have fibrosing cholestatic hepatitis (FCH),
following 12 or 24 weeks of Harvoni plus RBV. FCH is a rare and
severe form of recurrent hepatitis that occurs after liver
transplantation. It is associated with high morbidity and mortality
rates and there are no currently approved treatment options.
Cirrhosis and Portal
Hypertension
Study GS-US-334-0125 (ePoster LB #4283) evaluated 50 genotype
1-4 HCV-infected patients with cirrhosis and portal hypertension.
Patients were randomized to receive either 48 weeks of Sovaldi plus
RBV initially (n=25) or at the conclusion of a 24-week observation
period (n=21). Four patients in the observation arm discontinued
the study prior to receiving treatment. Of the patients who
received treatment with Sovaldi plus RBV, 72 percent (n=33/46)
achieved SVR12. A subset of 37 patients had paired hepatic venous
pressure gradient (HVPG) measurements at baseline and end of
treatment. Of these, 38 percent (14/37) of patients experienced a
≥10 percent reduction and 24 percent (9/37) of patients experienced
a ≥20 percent decrease in HVPG from baseline to end of treatment. A
baseline total bilirubin of <1.5 mg/dL was associated with a ≥20
percent decrease in HVPG (p=0.03). This study is the first to
demonstrate the effect of direct acting antivirals like Sovaldi on
HVPG, and additional assessments will be undertaken in these
patients one-year post treatment.
The safety and efficacy of these investigational uses of Harvoni
and Sovaldi have not been established.
Important Safety Information About
Harvoni
Warnings and Precautions
Risk of Serious Symptomatic Bradycardia When Coadministered
with Amiodarone: Amiodarone is not recommended for use with
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. 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 of Harvoni Due to P-gp
Inducers: Rifampin and St. John’s wort are not recommended for
use with Harvoni as they may significantly decrease ledipasvir and
sofosbuvir plasma concentrations.
Related Products Not Recommended: Harvoni is not
recommended for use with other products containing sofosbuvir
(Sovaldi).
Adverse Reactions
Most common (≥10 percent, all grades) adverse reactions were
fatigue and headache.
Drug Interactions
In addition to rifampin and St. John’s wort, coadministration of
Harvoni is also not recommended with carbamazepine, oxcarbazepine,
phenobarbital, phenytoin, rifabutin, rifapentine, and
tipranavir/ritonavir. Such coadministration is expected to decrease
the concentration of ledipasvir and sofosbuvir, reducing the
therapeutic effect of Harvoni.
Coadministration of Harvoni is not recommended with simeprevir
due to increased concentrations of ledipasvir and simeprevir.
Coadministration is also not recommended with rosuvastatin or
co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir
disoproxil fumarate due to increased concentrations of rosuvastatin
and tenofovir, respectively.
Consult the full Prescribing Information for Harvoni for more
information on potentially significant drug interactions, including
clinical comments.
Important Safety Information About
Sovaldi
Contraindications
Sovaldi combination treatment with ribavirin or with
peginterferon alfa plus ribavirin is contraindicated in women who
are pregnant or may become pregnant and men whose female partners
are pregnant because of the risk for birth defects and fetal death
associated with ribavirin. Contraindications to peginterferon alfa
and ribavirin also apply to Sovaldi combination treatment. Refer to
the prescribing information of peginterferon alfa and ribavirin for
a list of their contraindications.
Warnings and Precautions
Serious Symptomatic Bradycardia When Coadministered with
Amiodarone and Another HCV Direct Acting Antiviral (DAA):
Amiodarone is not recommended for use with Sovaldi 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.
Pregnancy: Use with ribavirin or peginterferon
alfa/ribavirin: Ribavirin therapy should not be started unless a
report of a negative pregnancy test has been obtained immediately
prior to initiation of therapy. Female patients of childbearing
potential and their male partners must use two forms of
non-hormonal contraception during treatment and for at least 6
months after treatment has concluded. Routine monthly pregnancy
tests must be performed during this time. Refer to the prescribing
information for ribavirin.
Use with Potent P-gp Inducers: Rifampin and St. John’s
wort should not be used with Sovaldi as they may significantly
decrease sofosbuvir plasma concentration, reducing its therapeutic
effect.
Adverse Reactions
Most common (≥20 percent, all grades) adverse reactions for:
Sovaldi + peginterferon alfa + ribavirin combination therapy
were fatigue, headache, nausea, insomnia, and anemia
Sovaldi + ribavirin combination therapy were fatigue, and
headache
Drug Interactions
In addition to rifampin and St. John’s wort, coadministration of
Sovaldi is not recommended with carbamazepine, oxcarbazepine,
phenobarbital, phenytoin, rifabutin, rifapentine, and
tipranavir/ritonavir. Such coadministration is expected to decrease
the concentration of sofosbuvir, reducing its therapeutic
effect.
About Gilead
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 that Gilead may observe unfavorable results from
additional clinical trials involving Sovaldi and Harvoni for
various difficult-to-treat patient groups, including patients with
decompensated cirrhosis, fibrosing cholestatic hepatitis C and
portal hypertension. 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 year ended December 31, 2014, 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 Sovaldi
and Harvoni is available at www.gilead.com.
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.
Gilead Sciences, Inc.Sung Lee, +1 650-524-7792 (Investors)Nathan
Kaiser, +1 650-522-1853 (Media)Michele Rest, +1 650-577-6935
(Media)
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