Gilead Announces Two-Year Data from Pivotal Phase III Studies Evaluating Viread(R) for Chronic Hepatitis B

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Two-Year

Gilead Announces Two-Year Data from Pivotal Phase III Studies Evaluating

Viread® for Chronic Hepatitis B

http://www.gilead.com

- No Resistance Observed Through Two Years of Treatment -

- Significant Viral Suppression Seen in Patients Switching to Viread –

SAN FRANCISCO--(BUSINESS WIRE)--Nov. 1, 2008--Gilead Sciences, Inc.

(Nasdaq:GILD) today announced the presentation of two-year (96-week) data from

two Phase III pivotal clinical trials, Studies 102 and 103, evaluating the

safety and efficacy of once-daily Viread® (tenofovir disoproxil fumarate)

among adult patients with chronic hepatitis B virus (HBV) infection. These data

will be presented during oral sessions at the annual meeting of the American

Association for the Study of Liver Diseases (The Liver Meeting 2008) being held

this week in San Francisco (October 31-November 4).

Studies 102 and 103 will evaluate treatment with Viread for up to eight years

among patients with HBeAg-negative and HBeAg-positive chronic hepatitis B,

respectively, with compensated liver disease. Patients in both studies were

originally randomized to receive Viread or Hepsera® (adefovir dipivoxil).

After the completion of 48 weeks of randomized blinded therapy, all eligible

patients were rolled over to open-label Viread monotherapy.

These new data show that patients who received Viread for up to 96 weeks

experienced sustained suppression of HBV levels in the blood (91 percent and 78

percent for Studies 102 and 103, respectively). The studies also show that all

Hepsera-treated patients whose HBV levels were suppressed at week 48 maintained

viral suppression after rolling over to Viread, while Hepsera-treated patients

with HBV DNA levels above 400 copies/mL at week 48 experienced significant viral

suppression after rolling over to Viread. Additionally, by week 96 of Study 103,

6 percent of all patients continuing treatment in both groups experienced " s "

antigen (HBsAg) loss, which contributes to resolution of chronic hepatitis B

infection (HBsAg seroconversion rates were 4 percent among patients originally

randomized to receive Viread and 5 percent for patients who rolled over from

Hepsera).

Notably, no mutations associated with resistance to Viread were reported among

patients receiving Viread monotherapy for up to 96 weeks or in Hepsera-treated

patients who rolled over to Viread.

" In this study, Viread produced a significant and sustained effect over two

years of treatment with no evidence of resistance, which is a substantial

clinical finding, " said Marcellin, MD of Hopital Beaujon in Clichy,

France, the principal investigator of Study 102. " Additionally, patients in this

study taking Hepsera were rolled over to Viread without new safety signals and

without compromising the efficacy of anti-HBV treatment. "

The U.S. Food and Drug Administration (FDA) approved Viread for chronic HBV in

adults in August 2008 based on earlier (48-week) results from these studies.

Viread and Hepsera are both manufactured by Gilead.

" One of the most important considerations in treating chronic hepatitis B is

resistance. It is reassuring to see that no patients from either arm of the

study demonstrated resistance to Viread at 96 weeks of treatment, " said

Heathcote, MD of the University of Toronto, Canada, the principal investigator

for Study 103. " It is also notable that 6 percent of HBeAg-positive patients

experienced " s " antigen loss. "

Chronic HBV affects an estimated 400 million people worldwide, including two

million people in the United States. Many are unaware that they are infected

because the disease may not produce obvious symptoms.

One in four people with chronic hepatitis B die from complications such as

cirrhosis and liver cancer. In the United States, Asian Americans are

disproportionately affected: Foreign-born Asians are 100 times more likely to

have the disease compared to non-Asians in the U.S. population. In September

2008, partly in response to advances in HBV therapy, the U.S. Centers for

Disease Control and Prevention (CDC) published new HBV screening guidelines

recommending that all individuals from Asian countries be tested for the

disease.

In addition to its indication for HBV, Viread is also indicated in combination

with other antiretroviral agents for the treatment of HIV infection in adults,

and is currently the most-prescribed molecule in antiretroviral therapy in the

United States.

About Studies 102 and 103

Studies 102 and 103 were multi-center, randomized, double-blind Phase III

clinical trials comparing Viread to Hepsera among patients with compensated

liver disease and HBeAg-negative presumed pre-core mutant (n=375) and

HBeAg-positive (n=266) chronic hepatitis B, respectively. The majority of

patients were treatment-naive, although some patients (n=75) were

lamivudine-experienced.

Patients originally randomized to Hepsera in both studies rolled over to Viread

(n=196) at week 48, while patients originally randomized to Viread continued

Viread treatment in the second 48 weeks (n=389). After 72 weeks, patients with

confirmed viremia (HBV DNA levels at or above 400 copies/mL on two consecutive

visits) had the option of adding emtricitabine treatment in the form of

Truvada®, an investigational product for the treatment of chronic hepatitis B.

Study 102 Results (Oral Presentation #146)

HBeAg-negative patients

Using a long-term evaluation, intent-to-treat analysis algorithm through 96

weeks, which excluded some patients who discontinued the study for

administrative reasons and had HBV DNA below 400 copies/mL at last study visit

(n=7), 91 percent of those originally randomized to Viread achieved HBV DNA

levels below 400 copies/mL compared to 89 percent of those originally randomized

to Hepsera who rolled over to Viread at week 48 (p=0.672).

Among patients who received Viread for the entire 96 weeks, 99 percent achieved

HBV DNA levels below 400 copies/mL. In addition, all patients who rolled over

from Hepsera to Viread at week 48, regardless of whether they were well

controlled on Hepsera or viremic, achieved viral load suppression below 400

copies/mL with Viread by week 96.

Two patients in Study 102 added emtricitabine treatment in the form of Truvada

between week 72 and week 96 due to confirmed viremia. One of these patients

achieved viral suppression by week 96 and is counted among the 91 percent of

patients who experienced sustained suppression with Viread throughout the

96-week period.

Levels of alanine aminotransferase (ALT, an enzyme that serves as a measure of

liver damage), which had been high at baseline, remained at near-normal levels

between 48 and 96 weeks of treatment in both Viread and Hepsera-to-Viread groups

(mean of 35 and 34 U/L, respectively, at week 96; p=0.827).

Viread was generally well tolerated by study subjects. The incidence of

drug-related serious adverse events was low, with one event reported in the

Viread group and none reported in the Hepsera-to-Viread group. There was one

death in the study, in the Viread group, due to metastatic liver carcinoma, a

known complication of chronic hepatitis B infection. The incidence of grade 3-4

laboratory abnormalities was 10 percent for both Viread and Hepsera-to-Viread

groups. No patients experienced a confirmed 0.5 mg/dL increase in serum

creatinine or creatinine clearance of less than 50 ml/min. No resistance to

Viread was detected among patients who received Viread monotherapy over two

years.

Study 103 Results (Oral Presentation #158)

HBeAg-positive patients

Using a long-term evaluation, intent-to-treat analysis algorithm through 96

weeks, which excluded some patients who discontinued the study for

administrative reasons and had HBV DNA below 400 copies/mL at last study visit

(n=8), 78 percent of those originally randomized to Viread achieved HBV DNA

levels below 400 copies/mL compared to 78 percent of those originally randomized

to Hepsera who rolled over to Viread at week 48 (p=0.801).

Among patients who received Viread for the entire 96 weeks, 89 percent achieved

HBV DNA levels below 400 copies/mL compared to 85 percent of patients who

remained on Viread at week 96 after switching from Hepsera at week 48 (p=0.374).

As in Study 102, all patients who were well controlled at week 48 on Hepsera

(n=12) maintained viral suppression after switching to Viread. Viremic Hepsera

patients responded rapidly after rolling over to Viread, with 82 percent

achieving HBV suppression below 400 copies/mL by week 96.

Twenty-eight patients in Study 103 added emtricitabine treatment in the form of

Truvada between 72 and 96 weeks due to confirmed viremia. Five of these patients

achieved viral suppression by week 96, two of whom were counted among the 78

percent of patients who experienced sustained suppression with Viread over 96

weeks and three of whom were counted among the 78 percent who achieved

suppression after rolling over from Hepsera.

As with Study 102, ALT levels, which had been elevated at baseline in both

patient groups, remained stable at near-normal levels by week 96 in both Viread

and Hepsera-to-Viread groups (mean of 35 and 39 U/L, respectively; p=0.765).

Among patients who continued treatment to week 96, a similar proportion of

patients in the Viread and Hepsera-to-Viread groups experienced HBeAg

seroconversion (26 percent versus 24 percent, respectively; p=NS).

Seroconversion is defined as both the disappearance of the hepatitis B " e "

antigen, a marker of HBV replication (rendering the patient " HBe-antigen

negative " ), and the appearance of antibodies specific for this antigen (making

the patient " HBe-antibody positive " ). In addition, 6 percent of patients in both

treatment groups experienced " s " antigen (HBsAg) loss, which contributes to

resolution of chronic hepatitis B infection (HBsAg seroconversion rates were 4

percent among patients originally randomized to receive Viread and 5 percent for

patients who rolled over from Hepsera).

As in Study 102, the incidence of drug-related serious adverse events was

similar between the Viread group (one patient) and the Hepsera-to-Viread group

(two patients). The incidence of grade 3-4 laboratory abnormalities was also

similar: 7 percent for the Viread-only patients and 10 percent for the

Hepsera-to-Viread patients. No patients experienced creatinine clearance of less

than 50 ml/min. Two patients in the Hepsera-to-Viread group had a confirmed 0.5

mg/dL increase in serum creatinine, compared to none in the Viread group. As

with Study 102, no resistance was detected among patients who received Viread

monotherapy over two years.

Continued treatment with Viread for 96 weeks did not reveal any new adverse

reactions and no change in the tolerability profile observed during the first 48

weeks of treatment. Treatment-related adverse events observed in greater than 5

percent of patients during the first 48 weeks of studies 102 and 103 included:

nausea, abdominal pain, diarrhea, headache, dizziness, fatigue, nasopharyngitis,

back pain and skin rash.

SOURCE: Gilead Sciences, Inc.