– Studies Highlight Progress with Approved Therapies and
Investigational Pangenotypic Regimens, Including Sofosbuvir/Velpatasvir
(SOF/VEL) and SOF/VEL Plus GS-9857 –
Gilead Sciences, Inc. (NASDAQ: GILD) today announced results from
several Phase 2 and Phase 3 studies evaluating its two investigational,
pangenotypic, fixed-dose combination therapies for the treatment of
chronic hepatitis C virus (HCV) infection, as well as new data
highlighting the potential use of Harvoni®
(ledipasvir/sofosbuvir) in adolescents aged 12 to 17. Data were
presented this week at The International Liver CongressTM
2016 in Barcelona, Spain.
“The data presented this week continue to underscore the high cure rates
and safety of our sofosbuvir-based HCV therapies, and support their
utility across all patient HCV genotypes and disease stages,” said
Norbert Bischofberger, PhD, Executive Vice President of Research and
Development and Chief Scientific Officer at Gilead. “We are pleased to
have the opportunity to further characterize the pangenotypic profiles
of our two new investigational fixed-dose combinations,
sofosbuvir/velpatasvir and sofosbuvir/velpatasvir plus GS-9857, and to
highlight results from the first study to evaluate interferon-free HCV
therapy in adolescents.”
Sofosbuvir/Velpatasvir (SOF/VEL)
Results from the open-label, Phase 3 ASTRAL-5 study (PS104), led by
David L. Wyles, MD, Associate Professor of Medicine, Division of
Infectious Diseases, University of California, San Diego, California,
evaluating once-daily SOF/VEL for 12 weeks among patients with HCV
genotype 1-6 who are co-infected with HIV demonstrated that SOF/VEL was
well-tolerated and resulted in high SVR12 rates. The SVR12 rate was 95
percent (n=99/104) overall, and 100 percent (n=19/19) and 97 percent
(n=28/29) in patients with cirrhosis and prior treatment-failure,
respectively. Two patients relapsed, while three patients were lost to
follow up or withdrew consent. Two patients achieved SVR4 but have not
yet returned for the post-treatment week 12 visit. The most common
adverse events (>10 percent) were fatigue and headache.
SOF/VEL is currently being evaluated by regulatory agencies in the
United States, Europe and Canada.
Sofosbuvir/Velpatasvir (SOF/VEL) Plus GS-9857
Data from three Phase 2 trials evaluating SOF/VEL plus GS-9857, a
pangenotypic protease inhibitor, (Studies GS-US-367-1168 and
GS-US-367-1169 and TRILOGY-3) also were selected for presentation.
Studies 1168 and 1169
Studies 1168 and 1169 evaluated 6 and 8 weeks of SOF/VEL plus GS-9857,
with or without ribavirin (RBV), among treatment-naïve patients and 12
weeks of SOF/VEL plus GS-9857 among patients who failed prior treatment
including those previously exposed to a direct acting antiviral (DAA)
regimen. Study 1168 evaluated 197 genotype 1 patients and Study 1169
evaluated 128 genotype 2-6 patients.
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Treatment-naïve patients: Poster SAT-138 highlighted combined
safety and efficacy results from Studies 1168 and 1169 evaluating
SOF/VEL plus GS-9857, with or without ribavirin, in genotype 1-6,
treatment-naïve patients, with and without cirrhosis. SVR12 rates
were:
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SOF/VEL plus GS-9857
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SOF/VEL plus GS-9857 with RBV
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6 weeks
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8 weeks
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8 weeks
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SVR12
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79% (n=53/67)
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96% (n=95/99)
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81% (n=25/31)
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The most common adverse events (>10 percent) across the three
study arms were headache, nausea, fatigue, diarrhea and anemia.
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Treatment-experienced patients: Oral presentation PS008
highlighted combined safety and efficacy results from Studies 1168
and 1169 evaluating 12 weeks of SOF/VEL plus GS-9857 in genotype
1-6, treatment-experienced patients. Twenty-seven percent of
patients were NS5A inhibitor-experienced, 52 percent were non-NS5A
inhibitor, DAA-experienced and 21 percent failed interferon-based
treatment without a DAA. Overall, the SVR12 rate was 99 percent
(n=127/128). One genotype 3 patient with cirrhosis who had failed
prior treatment with sofosbuvir plus pegylated
interferon/ribavirin relapsed. Frequently reported adverse events
(>10 percent) were headache, fatigue, diarrhea and nausea.
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Studies 1168 and 1169 were led by Edward J. Gane, MD, Auckland City
Hospital, Auckland, New Zealand (SAT-138); and Eric Lawitz, MD, Texas
Liver Institute, University of Texas Health Science Center, San Antonio,
Texas (PS008), respectively.
TRILOGY-3
A late-breaker oral presentation (PS021) featuring data from a Phase 2
trial, led by Dr. Lawitz, evaluated 12 weeks of a fixed-dose combination
of SOF/VEL/GS-9857, with or without RBV, among genotype 1,
DAA-experienced, HCV-infected patients, including patients with
cirrhosis. One hundred percent (n=24/24) of patients receiving 12 weeks
of therapy with SOF/VEL/GS-9857 and 96 percent (n=24/25) of patients
receiving SOF/VEL/GS-9857 plus RBV achieved SVR12. Among the 49 patients
in this trial, 41 percent had prior exposure to an NS5A inhibitor and 47
percent previously received at least two classes of DAA. The most common
adverse events (>10 percent) across both treatment arms were fatigue and
anemia.
Based on these data a fixed-dose combination of SOF/VEL/GS-9857 is being
evaluated in four Phase 3 studies (POLARIS-1, POLARIS-2, POLARIS-3 and
POLARIS-4). SOF/VEL/GS-9857 has been granted a Breakthrough Therapy
designation by the U.S. Food and Drug Administration for the treatment
of chronic genotype 1 HCV patients who have previously failed an NS5A
inhibitor-containing regimen.
Harvoni
Harvoni is the first single tablet HCV regimen approved in the United
States for use in a broad range of patient populations, including HCV
genotypes 1, 4, 5 and 6, HCV/HIV-1 coinfection, HCV genotype 1 and 4
liver transplant recipients and genotype 1-infected patients with
decompensated cirrhosis.
Data from an evaluation of Harvoni in genotype 1 HCV-infected
adolescents aged 12 to 17 have been selected for presentation in a late
breaker oral session (LB-4597). Presented by Sanjay Bansal, MD, MRCPCH,
Kings College Hospital, London, United Kingdom, and led by Kathleen B.
Schwarz, MD, Pediatric Liver Center, Johns Hopkins University School of
Medicine, Baltimore, Maryland, the Phase 2 study demonstrated that
Harvoni is well tolerated and results in high SVR12 in this population.
Of the 100 patients enrolled, 97 percent (n=97/100) achieved SVR12. The
three patients who did not achieve SVR12 were lost to follow up; no
patients experienced virologic failure. The most common adverse events
were headache, diarrhea and fatigue. Further evaluation of Harvoni in a
pediatric population of children aged 3 to 11 is ongoing.
Further information about the clinical studies described above can be
found at www.clinicaltrials.gov.
Uses for Harvoni in certain HCV patient populations highlighted above
are investigational and have not been determined to be safe or
efficacious. SOF/VEL and SOF/VEL/GS-9857 are investigational products
and have not been determined to be safe or efficacious.
Important Safety Information for Harvoni
Contraindications
If Harvoni is used in combination with ribavirin (RBV), all
contraindications, warnings and precautions, in particular pregnancy
avoidance, and adverse reactions to RBV also apply. Refer to RBV
prescribing information.
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%, all grades) adverse reactions were fatigue, headache
and asthenia.
Drug Interactions
In addition to rifampin and St. John’s wort, co-administration of
Harvoni is also not recommended with carbamazepine, oxcarbazepine,
phenobarbital, phenytoin, rifabutin, rifapentine, and
tipranavir/ritonavir. Such co-administration is expected to decrease the
concentration of ledipasvir and sofosbuvir, reducing the therapeutic
effect of Harvoni.
Co-administration of Harvoni is not recommended with simeprevir due to
increased concentrations of ledipasvir and simeprevir. Co-administration
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.
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 Gilead may observe unfavorable results from additional clinical
trials involving SOF/VEL, SOF/VEL/GS-9857 and Harvoni in certain patient
populations, including adolescents aged 12 to 18. In addition, the
regulatory filings for SOF/VEL and SOF/VEL/GS-9857 may not be approved
by regulatory agencies, and marketing approvals, if granted, may have
significant limitations on their use. 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, 2015, 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 Harvoni is available at www.gilead.com.
Harvoni is a registered trademark 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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