Gilead Sciences, Inc. (Nasdaq:GILD) today announced that Study
103, a Phase III clinical trial evaluating the company's once-daily
anti-HIV drug Viread(R) (tenofovir disoproxil fumarate or tenofovir
DF) 300 mg as a potential treatment for chronic hepatitis B virus
(HBV) infection, met its primary efficacy endpoint. The data show that
Viread is non-inferior to the company's once-daily antiviral drug
Hepsera(R) (adefovir dipivoxil) among patients with "e" antigen
(HBeAg)-positive chronic hepatitis B. The primary efficacy endpoint,
the proportion of patients with a complete response at week 48, was
defined by serum HBV DNA levels below 400 copies/mL and histologic
improvement characterized by at least a two point reduction in the
Knodell necroinflammatory score (a measure of necro-inflammation - an
inflammatory process in the liver including or leading to death of
liver cells) with no concurrent worsening of fibrosis (scarring of
liver tissue).
At 48 weeks, 66.5 percent of patients in the Viread arm (n=176)
had a complete response compared to 12.2 percent in the Hepsera arm
(n=90; p less than 0.001). The most commonly observed
treatment-emergent adverse events of moderate intensity or higher were
abdominal pain, back pain, headache, respiratory infections and
transaminase elevations. The incidence of these events was comparable
between the Viread and Hepsera arms of the study. In addition, the
most frequently observed grade 3 or 4 laboratory abnormalities were
elevations in transaminase and serum amylase and were comparable
between the two arms. Full study results will be submitted for
presentation at an upcoming scientific meeting.
Study 103 is the second of two Phase III pivotal studies
evaluating the efficacy, safety and tolerability of Viread for the
treatment of chronic hepatitis B to have met its primary efficacy
endpoint. Earlier this month, the company announced that the first
study (Study 102) met its primary 48-week efficacy endpoint showing
that Viread is non-inferior to Hepsera among patients with
HBeAg-negative/anti-HBe positive (presumed pre-core mutant) chronic
hepatitis B.
"The preliminary data observed in both Phase III trials evaluating
Viread as a potential treatment option for chronic hepatitis B are
very encouraging," said Franck Rousseau, MD, Vice President, Clinical
Research, Gilead Sciences. "We look forward to reviewing these data
with regulatory authorities and are working quickly to file a New Drug
Application in the United States and Marketing Authorisation
Application in Europe in the fourth quarter of this year."
The active ingredient in Viread, tenofovir DF, is currently the
most prescribed molecule in the United States for combination HIV
therapy. Viread received approval as an anti-HIV medication from the
U.S. Food and Drug Administration (FDA) in October 2001 and from the
European Commission in February 2002. Viread is not approved as a
treatment for chronic hepatitis B, and data from this analysis have
not been reviewed by the FDA.
Study Design
Study 103 is a multi-center, randomized, double-blind Phase III
clinical trial that compares the efficacy, safety and tolerability of
Viread and Hepsera over 48 weeks among patients with HBeAg-positive
chronic hepatitis B. Two hundred and sixty-six patients were
randomized in a 2:1 ratio to receive either Viread (300 mg once daily;
n=176) or Hepsera (10 mg once daily; n=90).
About Viread (tenofovir disoproxil fumarate)
In the United States, Viread is indicated in combination with
other antiretroviral agents for the treatment of HIV-1 infection.
Viread should not be used in combination with the fixed-dose
combination products Truvada(R) or Atripla(TM) because they already
contain Viread.
Lactic acidosis and severe hepatomegaly with steatosis, including
fatal cases, have been reported with the use of nucleoside analogues
alone or in combination with other antiretrovirals. Viread is not
approved for the treatment of chronic hepatitis B and the safety and
efficacy of Viread have not been established in patients coinfected
with HBV and HIV. Severe acute exacerbations of hepatitis B have been
reported in patients who have discontinued Viread. Hepatic function
should be monitored closely with both clinical and laboratory
follow-up for at least several months in patients who are co-infected
with HIV and HBV and discontinue Viread. If appropriate, initiation of
anti-hepatitis B therapy may be warranted.
Renal impairment, including cases of acute renal failure and
Fanconi syndrome, has been reported in association with the use of
Viread. It is recommended that creatinine clearance be calculated in
all patients prior to initiating therapy with Viread and as clinically
appropriate during therapy. Coadministration of Viread and didanosine
should be undertaken with caution. Patients should be monitored
closely for didanosine-associated adverse events, and didanosine
should be discontinued if these occur. Patients on atazanavir and
lopinavir/ritonavir plus Viread should be monitored for
Viread-associated adverse events, and Viread should be discontinued if
these occur. When co-administered with Viread, it is recommended that
atazanavir 300 mg be given with ritonavir 100 mg. Atazanavir without
ritonavir should not be co-administered with Viread.
Decreases in bone mineral density (BMD) at the lumbar spine and
hip have been seen with the use of Viread. The effects of
Viread-associated changes in BMD and biochemical markers on long-term
bone health and future fracture risk are unknown. Changes in body fat
have been observed in patients taking anti-HIV medicines. The cause
and long-term health effect of these changes are unknown. Immune
Reconstitution Syndrome has been reported in patients treated with
combination therapy, including Viread.
The most common adverse events among patients receiving Viread
with other antiretroviral agents in a pivotal clinical study (Study
903) were mild to moderate gastrointestinal events and dizziness.
Moderate to severe adverse events occurring in more than 5 percent of
patients receiving Viread included rash (rash, pruritis, maculopapular
rash, urticaria, vesiculobullous rash and pustular rash), headache,
pain, diarrhea, depression, back pain, fever, nausea, abdominal pain,
asthenia (weakness) and anxiety. In another pivotal study (Study 907),
less than 1 percent of patients discontinued participation because of
gastrointestinal events.
It is important for patients to be aware that anti-HIV medicines
including Viread do not cure HIV infection or AIDS and do not reduce
the risk of transmitting HIV to others. Full prescribing information
is available at www.GileadHIV.com.
The parent compound of Viread was discovered through a
collaborative research effort between Dr. Antonin Holy, Institute for
Organic Chemistry and Biochemistry, Academy of Sciences of the Czech
Republic (IOCB) in Prague and Dr. Erik DeClercq, Rega Institute for
Medical Research, Katholic University in Leuven, Belgium.
About Hepsera
Hepsera, a nucleotide analogue for the treatment of chronic
hepatitis B, works by inhibiting HBV DNA polymerase, an enzyme
involved in the replication of the virus in the body.
In the United States, Hepsera is indicated for the treatment of
chronic hepatitis B in adults with evidence of active viral
replication and either evidence of persistent elevations in serum
aminotransferases (ALT or AST) or histologically active disease.
The adverse reactions considered at least possibly related to
treatment reported in 3 percent or greater of patients in the first 48
weeks in Hepsera pivotal clinical studies were asthenia, headache,
abdominal pain, nausea, flatulence, diarrhea and dyspepsia. With
extended treatment, mild to moderate increases in serum creatinine
were observed uncommonly in patients with chronic hepatitis B and
compensated liver disease treated with Hepsera for a median of 49
weeks up to a maximum of 240 weeks. Changes in serum creatinine were
observed very commonly in patients pre- and post-transplantation with
lamivudine-resistant liver disease and multiple risk factors for
changes in renal function who were treated with Hepsera for up to 129
weeks, with a median time on treatment of 19 and 56 weeks,
respectively. Clinical and laboratory evidence of exacerbations of
hepatitis have occurred after discontinuation of treatment with
antiviral therapies for hepatitis B, including Hepsera. Special
warnings and precautions for use are included in the package insert
regarding monitoring of renal function, post-treatment exacerbations
of hepatitis, and the occurrence of lactic acidosis and severe
hepatomegaly with steatosis. Dosing instructions for patients with
underlying renal impairment and for patients co-infected with HIV are
also provided in the package insert, which is available for download
online at www.hepsera.com.
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 worldwide. Headquartered in
Foster City, California, Gilead has operations in North America,
Europe and Australia.
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 risks
related to Gilead's ability to successfully commercialize tenofovir DF
for chronic hepatitis B. For example, safety and efficacy data from
additional clinical studies may not warrant further development of
this compound for the treatment of chronic hepatitis B and completing
our clinical studies may take longer or cost more than expected. In
addition, feedback from regulatory authorities or results from
clinical trials might require modifications or delays in later stage
clinical trials or additional trials to be performed. Further, the FDA
and other regulatory authorities may not approve tenofovir DF for the
treatment of chronic hepatitis B, and marketing approval, if granted,
may have significant limitations on its use and physicians and may not
see advantages of tenofovir DF over other treatment options and may
therefore be reluctant to prescribe tenofovir DF for chronic hepatitis
B. 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, 2006 and its Quarterly Report on Form 10-Q for the first
quarter of 2007, 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.
Hepsera and Viread are registered trademarks of Gilead Sciences,
Inc.
For more information on Gilead, please call the Gilead Public
Affairs Department at 1-800-GILEAD-5 (1-800-445-3235) or visit
www.gilead.com.