– Results Presented at The Liver
Meeting® 2017–
Gilead Sciences, Inc. (NASDAQ: GILD) today announced results
from Phase 2 and Phase 3 studies of its approved medicines for
chronic hepatitis C virus (HCV) and hepatitis B virus (HBV)
infection, adding to the body of evidence supporting Gilead’s viral
hepatitis therapies in diverse patient populations. These and other
data from more than 25 abstracts will be presented this week at The
Liver Meeting® 2017, which begins today in Washington, D.C.
Positive results from studies of Harvoni® (ledipasvir
90mg/sofosbuvir 400mg) in HCV-infected patients with severe renal
impairment, Epclusa® (sofosbuvir 400mg/velpatasvir 100mg) in
HCV-infected liver transplant recipients and Vosevi® (sofosbuvir
400mg/velpatasvir 100mg/voxilaprevir 100mg) in NS5A-inhibitor
experienced HCV-infected patients will be presented during poster
sessions on October 21 and October 22. In addition, updated results
from two Phase 3 studies demonstrating improved long-term bone and
renal safety in HBV-infected patients one year after switching from
Viread® (tenofovir disoproxil fumarate 300mg) to Vemlidy®
(tenofovir alafenamide 25mg) will be presented on October 21.
“Gilead continues to study the effectiveness of our once-daily
sofosbuvir-based single tablet regimens in diverse chronic
HCV-infected patient populations to provide the opportunity for
cure for all patient populations, including those most difficult to
cure,” said Norbert Bischofberger, PhD, Executive Vice President of
Research and Development and Chief Scientific Officer at Gilead.
“We are also committed to advancing the long-term care of patients
with chronic HBV infection, and are pleased to share multiple new
data presentations demonstrating the ongoing improvements in bone
and renal safety observed when patients switch from Viread to
Vemlidy.”
Harvoni, Epclusa and Vosevi have Boxed Warnings in their product
labels regarding the risk of hepatitis B virus reactivation in
HCV/HBV coinfected patients, and Vemlidy has a Boxed Warning
regarding the risk of post-treatment severe acute exacerbation of
hepatitis B. See below for important safety information for all
products.
Harvoni in Renally Impaired Patients
(Poster #1587)
In an open-label Phase 2 study evaluating once-daily Harvoni for
12 weeks among HCV genotype 1 patients with severe renal impairment
(creatinine clearance ≤ 30 mL/min), 100 percent (18/18) of patients
achieved SVR12, including patients with compensated cirrhosis (n=2)
and those who had failed prior treatment (n=4).
Safety events were consistent with those expected for the
patient population. The most common adverse events (AEs) (>15
percent) were fatigue (22 percent), headache (22 percent) and
hyperkalemia (17 percent). Four patients (22 percent) reported
serious AEs, none of which was related to study drug. There were no
deaths and no patients discontinued treatment in the study.
Harvoni is approved for adults with chronic HCV genotype 1, 4, 5
or 6 infection without cirrhosis or with compensated cirrhosis,
adults with genotype 1 infection with decompensated cirrhosis in
combination with ribavirin (RBV), and adults with genotype 1 or 4
infection who are liver transplant recipients without cirrhosis or
with compensated cirrhosis, in combination with RBV. The safety and
efficacy of Harvoni have not been established in patients with
severe renal impairment.
Epclusa in Liver Transplant Patients
(Poster #1069)
In an open-label Phase 2 study evaluating once-daily Epclusa for
12 weeks among 79 liver transplant patients with genotype 1-4
chronic HCV infection, treatment with Epclusa resulted in an
overall SVR12 rate of 96 percent, including patients with cirrhosis
and prior treatment failure, and was well tolerated.
Patient Population SVR12
Patient Population SVR12 Genotype 1
95%(35/37)
Genotype 1-4 without cirrhosis
97%(70/72)
Genotype 2
100%(3/3)
Genotype 1-4 with cirrhosis
86%(6/7)
Genotype 3
97%(34/35)
Genotype 1-4, treatment-naïve
94%(30/32)
Genotype 4
100%(4/4)
Genotype 1-4, treatment-experienced
99%(46/47)
Baseline resistance mutations did not impact SVR rates. Two
patients relapsed in this study – one treatment-naïve non-cirrhotic
patient with HCV genotype 1a and one treatment-experienced
non-cirrhotic patient with HCV genotype 3.
Common adverse effects (AEs) (>10 percent) were headache (24
percent), fatigue (20 percent) and cough (10 percent). Three
patients (4 percent) experienced serious AEs; none was related to
study drug. One patient discontinued treatment after one week due
to hyperglycemia. There were no deaths, graft loss or episodes of
acute liver transplant rejection.
Epclusa is approved for patients with genotype 1-6 without
cirrhosis or with compensated cirrhosis, and in combination with
RBV for patients with decompensated cirrhosis. The safety and
efficacy of Epclusa in liver transplant recipients has not been
established.
Vosevi in NS5A Treatment-Experienced
Patients (Poster #1178)
A deferred treatment cohort of the POLARIS-1 Phase 3 study
confirmed previously reported results demonstrating the
effectiveness of 12 weeks of Vosevi as salvage therapy for
treatment-experienced patients. The study evaluated once-daily
Vosevi in NS5A-inhibitor experienced patients with chronic HCV who
were initially randomized to receive placebo in POLARIS-1.
Vosevi treatment was associated with an overall SVR12 rate of 97
percent (143/147), with 97 percent (141/145) of genotype 1 patients
achieving SVR12 and 100 percent (2/2) of genotype 6 patients
achieving SVR12. Four patients experienced virologic relapse after
completing treatment.
The most common adverse effects (>10 percent) were fatigue
(21 percent), headache (20 percent), diarrhea (19 percent) and
nausea (14 percent). Six patients (4 percent) experienced serious
AEs unrelated to study drug, and there were no discontinuations due
to AEs.
Vosevi is approved for patients without cirrhosis or with
compensated cirrhosis who have HCV genotype 1, 2, 3, 4, 5 or 6 and
have been previously treated with an NS5A inhibitor-containing
regimen, or with genotype 1a or 3 previously treated with a
sofosbuvir-containing regimen without an NS5A inhibitor.
Vemlidy in Patients Switching from
Viread (Poster #904) and Two Year Resistance Analysis (Oral
#26)
A post-hoc analysis of a subgroup of the 1,298 treatment-naïve
and treatment-experienced patients with chronic HBV infection from
two Phase 3 studies (Studies 108 and 110, Poster #904) demonstrated
that patients who were switched after 96 weeks of treatment with
Viread to Vemlidy experienced improvements in renal function, bone
mineral density (BMD) and serum alanine aminotransferase (ALT)
normalization while maintaining viral suppression, after 48 weeks
of treatment with Vemlidy.
In patients initially randomized to Viread, high rates of
virologic control (HBV DNA <29 IU/mL) were maintained after
switching from Viread to Vemlidy. When assessed at Week 96
(pre-switch), 88 percent of Viread patients (156/177) had achieved
virologic suppression. When these patients were switched to
Vemlidy, 89 percent (149/167) had achieved virologic suppression at
Week 144.
Median creatinine clearance (CrCL) increased among switch
patients by 3.6 (-3.6, +9.0) ml/min (p<0.001). Mean hip BMD
(n=180) increased by 0.96 percent (2.41) (p<0.001) and spine BMD
(n=181) increased by 1.83 percent (3.20) (p<0.001). In addition,
rates of serum ALT normalization (by the AASLD criteria) increased
from 47 percent of patients pre-switch at Week 96 to 65 percent
after 48 weeks of Vemlidy (p<0.001).
A prespecified analysis that will be presented during an oral
session (Oral #26) evaluated virologic resistance after 96 weeks of
treatment with Vemlidy or Viread. Of the 1,242 patients who entered
year two of treatment, similar percentages of patients treated with
Vemlidy (10.5 percent; 87/828) or Viread (10.9 percent; 45/414)
qualified for evaluation. Using genotypic and phenotypic analyses,
no resistance to either Vemlidy or Viread was detected in any
patients at 96 weeks.
Vemlidy is approved for the treatment of chronic HBV infection
in adults with compensated liver disease. The safety and efficacy
of switching virologically suppressed patients onto Vemlidy have
not been established.
Important Safety Information About
Harvoni, Epclusa and Vosevi
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 Harvoni, Epclusa, or Vosevi. 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.
Contraindications
- Harvoni and Epclusa: When 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.
- Vosevi is contraindicated with
rifampin.
Warnings and Precautions
- Serious Symptomatic Bradycardia When
Coadministered with Amiodarone: Amiodarone is not recommended
for use with Harvoni, Epclusa, or Vosevi 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 Harvoni, Epclusa, or Vosevi. P-gp inducers
may significantly decrease ledipasvir, sofosbuvir, velpatasvir,
and/or voxilaprevir plasma concentrations. Moderate to potent
inducers of CYP2B6, CYP2C8 or CYP3A4 may significantly decrease
sofosbuvir, velpatasvir, and/or voxilaprevir plasma
concentrations.
Adverse Reactions
- The most common adverse reactions
(≥10%, all grades) with Harvoni were fatigue, headache, and
asthenia.
- The most common adverse reactions
(≥10%, all grades) with Epclusa were headache and fatigue; and when
used with RBV in decompensated cirrhotics were fatigue, anemia,
nausea, headache, insomnia, and diarrhea.
- The most common adverse reactions
(≥10%, all grades) with Vosevi were headache, fatigue, diarrhea,
and nausea.
Drug Interactions
- 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.
- 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.
- Vosevi: Coadministration is not
recommended with phenytoin, phenobarbital, oxcarbazepine,
rifabutin, rifapentine, atazanavir, lopinavir,
tipranavir/ritonavir, efavirenz, rosuvastatin, pitavastatin, and
cyclosporine due to changes (decreased or increased) in
concentrations of sofosbuvir, velpatasvir, voxilaprevir, and/or the
other agent.
Consult the full Prescribing Information for Harvoni, Epclusa,
and Vosevi for more information on potentially significant drug
interactions, including clinical comments.
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 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)
through Week 48 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 AdministrationDosage: 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 Gilead may observe unfavorable results from
additional clinical trials involving Harvoni, Epclusa, Vosevi and
Vemlidy in certain difficult-to-treat patient populations. 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 June 30, 2017, 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,
Epclusa, Vosevi, Vemlidy and Viread including BOXED WARNING,
is available at www.gilead.com.
Harvoni, Epclusa, Vosevi, 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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