by John C. Martin
Article Date: 09-08-04

People who aren't responsive to conventional hepatitis treatment may
find answers in an alternative therapy if the results of a series of
ongoing clinical trials are positive. In the latest safety and
efficacy trial currently underway, more than 500 patients with
hepatitis C are being given a type of treatment known as Interferon
alfacon-1, also known as Infergen (INN-fer-jen), a type of consensus
interferon.1

A Different Indication
This medication is currently approved in the U.S. as a therapy for
chronic hepatitis C (HCV). But it does not currently target patients
who haven't responded previously to combination treatment with
pegylated interferon and ribavirin. The aim of this trial, based on
positive results from preclinical research, is to test the safety
and efficacy of the drug in hepatitis C non-responders.

"HCV nonresponders represent a growing unmet medical need because
retreatment options are limited and generally provide very poor
response rates," said Robert Carithers, MD, a hepatologist at the
University of Washington Medical Center, and the trial's chief
investigator. "Pilot studies of daily Infergen plus ribavirin in the
U.S. and Europe have shown promising response rates in the treatment
of nonresponders. We hope to confirm these preliminary findings in
this large, well-controlled Phase III study."

Other Trials of Infergen
Two of those pilot studies were released at Digestive Disease Week,
a gastroenterology conference held this past spring. In the first
trial,2 doctors gave patients either Infergen monotherapy or
Infergen combined with ribavirin. They discovered sustained
virologic response (SVR) rates of up to 27% in the patients. In the
second pilot study,3 137 patients who had previously failed to
respond to pegylated interferon/ribavirin therapy were
retrospectively assessed for their response to Infergen therapy
combined with ribavirin. After 48 weeks, 43 percent of the patients
achieved an end-of-treatment response, the investigators reported.

"The results of those studies provide strong scientific rationale
for a Phase III study of daily Infergen plus ribavirin," explained
Dan Welch, President and CEO of Intermune, in a statement.

The DIRECT Trial
Based on those encouraging findings, doctors launched the latest
clincal trial, a Phase III randomized, open label study known as
DIRECT, in which 510 patients are being given either 9 or 15
micrograms (mcg) of Infergen, and up to 1200 mg of ribavirin—based
on an individual patient's weight—once per day for 48 weeks. In a
third group of patients, no treatment is being given, as a
comparison. Unlike a blinded study, patients and clinical staffers
in an open-label trial like this one are aware of whether a patient
is being given a drug being tested, or a placebo. Open label trials
aren't as strong as blinded trials because of the risk of bias that
could occur.

Patients in the non-treatment arm of the trial who have less than a
specified reduction in viral levels at 24 weeks into the study may
be eligible to then receive Infergen treatment at that point, the
investigators stated.

The researchers in the study are looking for sustained virologic
responses (SVRs)—defined as undetectable viral levels—at 68 and 72
weeks after the start of therapy. They also plan to measure non-
detectable viral loads at weeks 24 and 48, as well as the percentage
of patients who have converted from abnormal to normal liver enzyme
levels. Liver enzymes are released by the liver into the bloodstream
when it becomes damaged. Doctors use levels of the enzymes as
indicators of liver disease when conducting clinical tests.4

Concurrent Study Underway
"In addition to this Phase III trial, we are simultaneously
conducting a Phase II study to assess the use of daily Infergen in
combination with our other marketed interferon, Actimmune®
(interferon gamma 1-b), in the treatment of HCV non-responders,"
Welch said.

Actimmune is currently indicated as a therapy for two congenital
diseases: chronic granulomatous disease, and severe, malignant
osteopetrosis, according to Intermune.