Biotech Values

[DewDiligence]

GILD’s Viread clearly works in HBV and it evidently
works better than its close chemical cousin, Hepsera
(#msg-20250616). This PR shows the results of the
second of two phase-3 trials, which tested Viread vs
Hepsera in patients who were “e-positive” (i.e. positive
for the HBeAg antigen). Compared to “e-negative”
patients—who were tested in the first Viread phase-3
trial—e-positive patients are typically harder to get to
an undetectable viral level; however, for patients who
do achieve an undetectable viral level, those who are
e-positive stand a better chance of having their viral
level remain undetectable on a long-term basis.

In the e-positive trial reported here, Viread produced a
“complete response” in 66.5% of patients vs 12.2% for
Hepsera, a delta of 53.3 percentage points that easily
met the non-inferiority goal of the trial. (Superiority
of Viread to Hepsera was not formally tested but would
have been achieved rather easily if it had been.) This
compares to complete-response rates of 70.8% and
48.8% for Viread and Hepsera, respectively, in the
e-negative phase-3 trial, a delta of 22.0 percentage
points (#msg-20244553).

Based on these two phase-3 trials, it’s clear that Viread
stands to take market share from Hepsera, eventually.
However, this may not happen in a big way until there
are ample data to show that Viread continues to be safe
and effective beyond 48 weeks.

The more interesting question is whether Viread will
take share from Baraclude and Tyzeka. I think it
probably won’t because the best treatment for chronic
HBV will likely turn out to be a combination of a
nucleoside (Baraclude, Tyzeka, Clevudine) and a
nucleotide (Viread, Hepsera). However, this hypothesis
must be proven empirically.

An ancillary issue with using Viread to treat HBV is
that it is highly active against HIV. (It is a component
of the Atripla and Truvada backbone combinations for
first-line treatment of HIV.) This may be disadvantageous
in treating HBV/HIV co-infected patients because it may
cause resistance to HIV prematurely if the HBV infection
is attacked first.

http://biz.yahoo.com/bw/070625/20070625005394.html?.v=1

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Second Phase III Study Evaluating Gilead's Viread for the Treatment of Chronic HBV Meets Primary Endpoint

Monday June 25, 8:30 am ET

FOSTER CITY, Calif.--(BUSINESS WIRE)--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® (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® (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). [This is the same primary endpoint as the one used in the first phase-3 trial: the one in e-negative patients (#msg-20244553).]

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).
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