Gilead Sciences, Inc. (NASDAQ:GILD) today announced that the European
Commission has granted marketing authorisation for Viread® (tenofovir disoproxil fumarate) for the treatment of chronic hepatitis B
in all 27 member states of the European Union.
A once-daily tablet, Viread works by blocking hepatitis B virus (HBV)
DNA polymerase, the enzyme that is necessary for the virus to replicate
in liver cells. Viread has been approved in the European Union for use
in adult chronic HBV patients with compensated liver disease, with
evidence of active viral replication, persistently elevated serum
alanine aminotransferase (ALT) levels and histological evidence of
active inflammation and/or fibrosis. The product was recently approved
for the treatment of chronic hepatitis B in Turkey and New Zealand, and
marketing applications are currently pending regulatory review in the
United States, Canada and Australia.
"Hepatitis B is a significant problem in
Europe, where approximately 20,000 people die of complications from the
disease each year," said Patrick Marcellin
MD, PhD, Professor of Hepatology at the University of Paris and Head of
the Viral Hepatitis Research Unit (INSERM) at the Hôpital
Beaujon in Clichy, France. "As a physician and
researcher who has studied this drug extensively in large-scale clinical
trials, I believe Viread is an important treatment option for patients
who are just starting therapy, as well as for those who may have
had previous experience with other medications, including lamivudine."
Today´s approval is based primarily on data
from two ongoing Phase III clinical trials, Studies 102 and 103, in
patients (n = 375) chronically infected with HBV who were new to HBV
therapy (treatment-naive). Some patients (n=51) in the Phase III trials
have had previous experience with lamivudine (treatment-experienced).
These studies evaluate the efficacy, safety and tolerability of Viread
compared to Hepsera® (adefovir dipivoxil). Positive data from these studies were presented in
late-breaker presentations at the annual meeting of the American
Association for the Study of Liver Diseases in Boston, Massachusetts
November 2007. Additional 72-week data from these studies were presented
at the annual meeting of the European Association for the Study of the
Liver in Milan, Italy, April 23-27.
"Data from studies 102 and 103 demonstrate
that Viread has many of the preferred qualities of an antiviral
treatment: rapid and profound viral suppression, a
well-established safety profile with more than one million years of
patient experience, and convenient once-daily administration," said Kevin Young, Executive Vice President, Commercial Operations at
Gilead Sciences. "Now that Viread is approved
for chronic hepatitis B in Europe, our top priority is working to ensure
that all individuals who need the medication have access to it as
quickly as possible."
Viread represents Gilead´s second once-daily antiviral for the treatment
of chronic hepatitis B; the first, Hepsera, is currently widely used as
a treatment for chronic hepatitis B in Europe. In addition, the company
is also developing small molecule compounds for the treatment of
hepatitis C and a hepatoprotectant for hepatitis-related liver fibrosis.
Viread has been available in Europe as a part of combination therapy for
HIV infection in adults since 2002. Its active ingredient, tenofovir
disoproxil, is the most widely prescribed molecule for the treatment of
HIV infection in several European Union nations.
About Chronic Hepatitis B
Chronic hepatitis B is a common and potentially fatal liver disease
caused by the hepatitis B virus, which is up to 100 times more easily
transmitted than HIV. Chronic hepatitis B can produce no symptoms in its
earlier stages, meaning many individuals are unaware that they are
infected until they have advanced liver disease. Complications commonly
associated with chronic hepatitis B include scarring of the liver
(cirrhosis), liver failure and liver cancer. More than 400 million
people are estimated to be chronically infected with HBV worldwide and
without treatment, up to one quarter of those will ultimately die of
liver disease.
About Viread (tenofovir disoproxil
fumarate) for HIV
In the United States, Viread is indicated in combination with other
antiretroviral agents for the treatment of HIV-1 infection.
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 HBV infection 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 treatment may be
warranted.
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.
Renal impairment, including cases of acute renal failure and Fanconi
syndrome (renal tubular injury with severe hypophosphatemia), 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.
Routine monitoring of calculated creatinine clearance and serum
phosphorous should be performed in patients at risk for renal
impairment. Dosing interval adjustment and close monitoring of renal
function are recommended in all patients with creatinine clearance less
than 50mL/min. Viread should be avoided with concurrent or recent use of
a nephrotoxic agent.
The U.S. package insert advises that co-administration 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 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 effect on long-term bone health
and future fracture risk is unknown. Cases of osteomalacia (associated
with proximal renal tubulopathy) have been reported in association with
the use of Viread.
Changes in body fat have been observed in patients taking anti-HIV
medicines. The mechanism 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.
For full prescribing information outside of the United States physicians
should consult their local product labeling.
About Hepsera (adefovir dipivoxil)
In the United States, Hepsera is indicated for the treatment of chronic
hepatitis B in patients 12 years of age and older with evidence of
active viral replication and either evidence of persistent elevations in
serum aminotransferases (ALT or AST) or histologically active disease.
Hepsera is not recommended for use in children less than 12 years of age.
Severe acute exacerbations of hepatitis have been reported in patients
who have discontinued anti-hepatitis B therapy, including Hepsera.
Hepatic function should be closely monitored in both clinical and
laboratory follow-up for at least several months in patients who
discontinue hepatitis B therapy. If appropriate, resumption of therapy
may be warranted. In patients at risk of having underlying renal
dysfunction, chronic administration of Hepsera may result in
nephrotoxicity. These patients should be monitored closely for renal
function and may require dose adjustment. Dose adjustment is recommended
in patients with serum creatinine less than 50 mL/min. HIV resistance
may emerge in chronic hepatitis B patients with unrecognized or
untreated HIV infection treated with anti-hepatitis B therapies, such as
therapy with Hepsera, that may have activity against HIV. Lactic
acidosis and severe hepatomegaly with steatosis, including fatal cases
have been reported with the use of nucleoside analogs alone and in
combination with other antiretrovirals.
Adverse reactions identified from placebo-controlled and open label
studies include the following: asthenia, headache, abdominal pain
diarrhea, nausea, dyspepsia, flatulence, increased creatinine, and
hypophosphatemia. Additional adverse reactions observed from an
open-label study in pre- and post-transplant patients include abnormal
renal function, renal failure, vomiting, rash and pruritus.
For full prescribing information outside of the United States
physicians should consult their local product labeling.
Viread and Hepsera are the result of 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 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.
U.S. full prescribing information for Viread is available at www.Viread.com
U.S. full prescribing information for Hepsera is available at www.Hepsera.com
Viread and Hepsera 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.
