European Commission Approves Viread (R) for Chronic Hepatitis B

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.