[November 14, 2015] |
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Gilead Presents New Data at The Liver Meeting 2015
Gilead Sciences, Inc. (Nasdaq:GILD) today announced it will present
results from multiple studies of Viread® (tenofovir
disoproxil fumarate, TDF (News - Alert)) 300 mg for the treatment of chronic hepatitis
B virus (HBV) infection, as well as new data regarding its
investigational agents for HBV and nonviral liver diseases, including
nonalcoholic steatohepatitis (NASH) and primary sclerosing cholangitis
(PSC), at The Liver Meeting 2015 taking place November 13-17 in San
Francisco.
"The data accepted for presentation this week underscore Gilead's
ongoing commitment to advancing the care of people living with
progressive liver diseases," said Norbert Bischofberger, Ph.D.,
Executive Vice President of Research and Development and Chief
Scientific Officer at Gilead. "In addition to long-term data for Viread
for patients with HBV, we are pleased to present data that advances our
understanding of a number of new compounds in our pipeline that may have
the potential to address unmet needs in HBV, as well as in NASH and PSC
- two diseases for which there currently are no approved treatment
options."
Viread
Approved for chronic HBV in 2008, Viread is currently the most
prescribed therapy for a disease that affects more than 350 million
people worldwide. Five-year data presented this week support the durable
antiviral efficacy and consistent safety and resistance profile of
Viread (Posters #2004 and #1678). Data also demonstrate the
investigational role of Viread in reducing perinatal transmission of HBV
from highly viremic mothers (Oral #209).
Liver Disease Pipeline
Hepatitis B - TAF (tenofovir alafenamide), GS-9620 and GS-4774 TAF,
a novel targeted prodrug of tenofovir, has demonstrated potent antiviral
efficacy at a dose less than one-tenth that of Viread, as well as
improvements in renal and bone safety laboratory markers in several
Phase 3 studies for the treatment of HIV infection. Phase 3 results for
TAF in patients with chronic HBV infection are expected by the end of
2015. Results being presented this week include a study demonstrating
the antiviral activity of TAF against drug-resistant HBV isolates
(Poster #2021).
The company will also present data highlighting two investigational
compounds, the oral TLR-7 agonist GS-9620 and GS-4774, a therapeutic
T-cell vaccine. These compounds are designed to stimulate the innate
(GS-9620) and T-cell (GS-4774) responses to HBV, which may be important
to cure patients with chronic HBV infection. Data presented include in
vitro studies exploring the cellular mechanisms of antiviral response to
GS-9620 (Oral #35 and Poster #2009), and results from a Phase 2 study of
GS-4774 in virally-suppressed patients with chronic HBV (Poster #2015)
and the associated immunologic and biologic responses observed in the
trial (Poster #2052).
NASH and PSC Gilead is investigating two compounds
(simtuzumab and GS-4997) for their utility in treating NASH and PSC.
NASH results from metabolic dysfunction that is associated with
steatosis (fat within the liver), which leads to inflammation,
hepatocellular injury and progressive fibrosis. It may also lead to
cirrhosis and is expected to become the leading indication for liver
transplantation by 2020. PSC is a disease characterized by inflammation
and stricturing of the bile ducts. PSC eventually can also lead to
cirrhosis and other complications, including bile duct cancer.
GS-4997, an apoptosis signal-regulating kinase (ASK1) inhibitor, is
currently being evaluated in a Phase 2 study of patients with NASH and
moderate to severe liver fibrosis. Simtuzumab, an anti-lysyl
oxidase-like-2 (LOXL2) antibody, is being evaluated for the treatment of
NASH and PSC in ongoing Phase 2b trials.
Three abstracts were accepted for poster presentations that
characterized in animal models the effects of simtuzumab alone (Poster
#1379), GS-4997 alone (Poster #1359), and the combination of simtuzumab
and GS-4997 on fibrosis and portal hypertension (Poster #1367).
Nine abstracts were also accepted for presentation as posters that
characterize the patient populations enrolled in the ongoing Phase 2b
trials of simtuzumab in NASH and PSC, respectively. These included the
baseline disease associations of serum LOXL2, histology and portal
pressure in these patient populations (Posters #616, #624, #632, #737,
#739, #1428, #1435, #2149 and #2239).
Further information about the clinical studies described above can be
found at www.clinicaltrials.gov.
Abstracts for Gilead's presentations can be accessed at http://www.aasld.org/sites/default/files/2015SupplementFULLTEXT.pdf
GS-4774, GS-4997, GS-9620, simtuzumab and TAF are investigational
products and have not been determined to be safe or efficacious.
Important Safety Information About Viread for
Chronic Hepatitis B
BOXED WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and
POST TREATMENT EXACERBATION OF HEPATITIS
-
Lactic acidosis and severe hepatomegaly with steatosis, including
fatal cases, have been reported with the use of nucleoside analogs,
including Viread, in combination with other antiretrovirals
-
Severe acute exacerbations of hepatitis have been reported in
HBV-infected patients who have discontinued anti-hepatitis B therapy,
including Viread. 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 Viread.
If appropriate, resumption of anti-hepatitis B therapy may be warranted
Warnings and precautions
-
New onset or worsening renal impairment: Cases of acute renal
failure and Fanconi syndrome have been reported with the use of
Viread. In all patients, assess estimated creatinine clearance (CrCl)
prior to initiating and during therapy. In patients at risk for renal
dysfunction, including those who previously experienced renal events
while receiving adefovir dipivoxil, additionally monitor serum
phosphorus, urine glucose, and urine protein. In patients with CrCl
<50 mL/min, adjust dosing interval and closely monitor renal function.
Avoid concurrent or recent use with a nephrotoxic agent. Cases of
acute renal failure, some requiring hospitalization and renal
replacement therapy, have been reported after initiation of high dose
or multiple NSAIDs in HIV-infected patients with risk factors for
renal dysfunction; consider alternatives to NSAIDs in these patients.
Persistent or worsening bone pain, pain in extremities, fractures
and/or muscular pain or weakness may be manifestations of proximal
renal tubulopathy and should prompt an evaluation of renal function.
-
Coadministration with other products:
- Do not use in
combination with other products containing tenofovir disoproxil
fumarate - Do not administer in combination with adefovir
dipivoxil
-
Patients coinfected with HIV-1 and HBV: Due to the risk of
development of HIV-1 resistance, Viread should only be used in HIV-1
and HBV coinfected patients as part of an appropriate antiretroviral
combination regimen. HIV-1 antibody testing should be offered to all
HBV-infected patients before initiating therapy with Viread.
-
Bone effects: Decreases in bone mineral density (BMD) and
mineralization defects, including osteomalacia, have been seen in
patients treated with Viread. Consider assessment of BMD in adult and
pediatric patients who have a history of pathologic bone fracture or
other risk factors for bone loss. In a clinical trial conducted in
pediatric subjects 12 to <18 years of age with chronic hepatitis B,
total body BMD gain was less in Viread -treated subjects as compared
to the control group. In patients at risk of renal dysfunction who
present with persistent or worsening bone or muscle symptoms,
hypophosphatemia and osteomalacia secondary to proximal renal
tubulopathy should be considered
Adverse Reactions
-
In HBV-infected subjects with compensated liver disease: Most
common adverse reaction (all grades) was nausea (9%). Other
treatment-emergent adverse reactions reported in >5% of patients
treated with Viread included: abdominal pain, diarrhea, headache,
dizziness, fatigue, nasopharyngitis, back pain, and skin rash
-
In HBV-infected subjects with decompensated liver disease: Most
common adverse reactions (all grades) reported in =10% of patients
treated with Viread were abdominal pain (22%), nausea (20%), insomnia
(18%), pruritus (16%), vomiting (13%), dizziness (13%), and pyrexia
(11%)
Drug Interactions (News - Alert)
-
Didanosine: Coadministration increases didanosine
concentrations. Use with caution and monitor for evidence of
didanosine toxicity (e.g., pancreatitis, neuropathy). Didanosine
should be discontinued in patients who develop didanosine-associated
adverse reactions. In patients weighing >60 kg, the didanosine dose
should be reduced to 250 mg once daily when it is coadministered with
Viread and in patients weighing <60kg, the didanosine dose should be
reduced to 200 mg once daily when coadministered with Viread
-
HIV-1 protease inhibitors: Coadministration decreases
atazanavir concentrations and increases tenofovir concentrations; use
atazanavir given with ritonavir. Coadministration of Viread with
atazanavir and ritonavir, darunavir and ritonavir, or
lopinavir/ritonavir increases tenofovir concentrations. Monitor for
evidence of tenofovir toxicity
-
Drugs affecting renal function: Coadministration of Viread with
drugs that reduce renal function or compete for active tubular
secretion may increase concentrations of tenofovir
Dosage and Administration
-
Recommended dose, in adults and pediatric patients =12 years of age
(=35 kg), for the treatment of chronic hepatitis B: one 300 mg tablet,
once daily, taken orally, without regard to food
-
In the treatment of chronic hepatitis B, the optimal duration of
treatment is unknown
-
Safety and efficacy in pediatric patients <12 years of age or weighing
<35kg with chronic hepatitis B have not been established
-
The dosing interval of VIREAD should be adjusted and renal function
closely monitored in patients with baseline creatinine clearance
(CrCL) <50 mL/min. For patients with CrCL 30-49mL/min, the interval is
every 48 hours and with CrCL 10-29mL/min, the interval is every 72-96
hours. For hemodialysis patients, the interval is every 7 days or
after a total of approximately 12 hours of dialysis. Consult the full
Prescribing Information for additional information.
-
The pharmacokinetics of tenofovir have not been evaluated in
non-hemodialysis patients with creatinine clearance <10 mL/min;
therefore, no dosing recommendation is available for these patients
-
No dose adjustment is necessary for patients with mild renal
impairment (creatinine clearance 50-80 mL/min). Routine monitoring of
estimated creatinine clearance, serum phosphorus, urine glucose, and
urine protein should be performed in these patients
-
No data are available to make dose recommendations in pediatric
patients with renal impairment
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
possibility of unfavorable results from these studies and other ongoing
and subsequent clinical trials involving GS-4774, GS-4997, GS-9620,
simtuzumab, TAF and Viread. 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, 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 including BOXED WARNING for
Viread is available at www.gilead.com.
Viread is a registered trademark of Gilead Sciences, Inc.
For more information on Gilead Sciences, please visit the company's
website at www.gilead.com,
follow Gilead on Twitter (News - Alert) (@GileadSciences) or call Gilead Public Affairs
at 1-800-GILEAD-5 or 1-650-574-3000.
View source version on businesswire.com: http://www.businesswire.com/news/home/20151114005007/en/
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