Daily Consensus Interferon Shows Better Efficacy Against HCV Than Pegylated
Interferon

Martha Kerr
Medscape Medical News 2006. © 2006 Medscape

November 7, 2006 (Boston) - Interim results of the Daily-dose consensus
Interferon and Ribavirin Efficacy of Combined Therapy (DIRECT) trial were
announced here this week at the 57th annual meeting of the American
Association for the Study of Liver Diseases (AASLD).

This large, multicenter, randomized trial shows that daily treatment with
consensus interferon plus ribavirin has a response rate of between 20% to
25% in patients with hepatitis C virus (HCV) infection who failed to respond
to the currently approved pegylated formulation of interferon.

"Consensus interferon produces constant pharmacologic pressure on HCV. It
has good potency, with a shorter activity period.... In vitro studies have
shown that it is more potent than interferon alfa-2a and alfa-2b," principal
investigator Bruce Bacon, MD, director of the Division of Gastroenterology
and Hepatology at St. Louis University School of Medicine and comedical
director of the Saint Louis University Liver Center in Missouri, told
Medscape in an interview.

The DIRECT trial involved more than 500 patients with HCV infection who were
nonresponders to standard therapy. The study population included 77% with
advanced liver fibrosis.

Patients were randomized to 1 of 2 doses of consensus interferon combined
with ribavirin (1.0 - 1.2 g/day). Group 1 received 9 µg/day, group 2
received 15 µg/day and a third group received no treatment, with the
intention to randomize patients in the no-treatment group to 1 of the 2
active treatment group at 6 months if the DIRECT trial showed positive
results.

"Interim analysis of the efficacy [of consensus interferon] was about 25% at
48 weeks," Dr. Bacon announced. "Fifteen to twenty percent are showing a
sustained viral response, but that data is not in yet.... Some relapse was
expected." There was no change in status of patients randomized to no
treatment and they were subsequently randomized to active treatment.

"The incidence and type of adverse events were about the same as with
pegylated interferon. About 10% on the 9-µg dose and 15% on the 15-µg dose
discontinued treatment," Dr. Bacon said. "But remember, this is fairly
intensive therapy.

"These were nonresponders to the current best therapy for HCV," said Dr.
Bacon. "The robustness of the failure to respond was good, which is one
criticism of treatment response studies."

There has been some regression of fibrosis, which Dr. Bacon is watching with
interest. Data on that plus sustained efficacy data should be available in
the spring, and will be presented at the annual meeting of the European
Association for the Study of the Liver, he said.

Dr. Bacon's study is supported by a grant from Valiant Pharmaceuticals
International, and Dr. Bacon has disclosed a financial relationship with
Valiant.

Robert Brown, MD, associate professor of medicine at Columbia University
Medical Center in New York City and a specialist in digestive and liver
diseases, called consensus interferon "consistently intriguing" in an
interview with Medscape, "but we need to wait for the sustained efficacy
data.

"I don't see consensus interferon as a first-line agent," Dr. Brown
commented, "particularly because of its inconvenience, requiring daily
injections. In addition, you would end up overtreating hepatitis C patients
who may respond to pegylated interferon. That's why you need to give
patients about 12 weeks to show a response to peg-interferon.... You can
even predict response as early as 4 to 6 weeks in some nonresponders. You
could switch to consensus interferon then, or may be able to switch over to
another peg-interferon.

"What is another enormously exciting class of drugs [for the treatment of
HCV] are the new protease inhibitors," Dr. Brown said. "The investigational
agent VX-950 is one of these."

A study of VX-950 (Telaprevir, Vertex Pharmaceuticals, Inc) added to
pegylated interferon-alfa-2a and ribavirin after 28 days of the 2-drug
regimen, showed "a rapid and substantial antiviral effect," according to
John G. McHutchison, MD, professor of medicine and director of
gastroenterology and hepatology research at Duke University in Durham, North
Carolina. He and his colleagues in the multicenter trial of VX-950 studied
the triple-drug regimen in 12 treatment-naive patients infected with HCV
genotype 1.

The 3-drug regimen was well-tolerated and similar to that seen with
pegylated interferon and ribavirin alone.

All patients had undetectable viral levels after 28 days of treatment. In 2
patients, levels were undetectable within 8 days of adding the protease
inhibitor.

Twelve weeks after completion of VX-950 treatment, 11 patients continued to
have undetectable viral levels.

Dr. McHutchison has disclosed a financial relationship with Vertex
Pharmaceuticals, which funded the study.

Eugene R. Schiff, MD, professor of medicine and chief of the Division of
Hepatology at the University of Miami in Florida, said the findings "equate
to a cure of HCV. Unlike hepatitis B, HCV is not incorporated in the cell's
DNA, so you can get a cure."

"With these results, you will see many more patients come for treatment,"
Dr. Schiff told Medscape. "At a maximum, only about 10% are being treated
now."

Dr. Schiff receives funding from Pfizer Ltd for research in the field of HCV
treatment.

"The protease inhibitors could revolutionize the treatment of HCV. The next
2 years...are going to bring a lot of change," Dr. Brown asserted.

AASLD 57th Annual Meeting: Abstracts LB18 and 95. Presented October 30,
2006.