Although bevirimat demonstrated anti-HIV activity, plasma concentrations
obtained with the tested tablet formulation were lower than anticipated, suggesting
that the formulation used in that study could not deliver an adequate dose of
the drug.
Last week, the company announced that the U.S. Food and Drug
Administration has agreed to a revised trial design, which will allow higher doses
using a liquid formulation of bevirimat.
Below
is an excerpt from the Panacos press release announcing the agreement:
Panacos
Announces Bevirimat Phase 2b Dose Escalation Strategy Mar 12 2007, 3:02 PM
EST -- Business Wire -- Panacos Pharmaceuticals, Inc. (NASDAQ: PANC), a biotechnology
company dedicated to developing the next generation of antiviral therapeutic products,
today announced that the company and the US Food and Drug Administration (FDA)
have agreed to a revised trial design for the company's Phase 2b clinical study
of bevirimat (PA-457), the first-in-class maturation inhibitor for the treatment
of HIV infection. The first cohort in this study was completed in December 2006
and confirmed the antiviral activity of bevirimat shown in previous studies and
extended it to HIV patients failing therapy due to antiretroviral resistance.
However, the prototype tablet formulation used in that cohort resulted in bevirimat
plasma concentrations that were lower than anticipated.
The next cohorts
in the Phase 2b study will test the tolerability and efficacy of bevirimat in
treatment-experienced patients failing current therapy, at increasing doses using
the oral liquid formulation, which was utilized in the bevirimat Phase 2a trial.
Phase 2b dose escalation with the liquid formulation will involve 14-day "functional
monotherapy," where patients are dosed with either placebo or bevirimat in
combination with their failing antiretroviral therapy. This is similar to the
first Phase 2b cohort, except that patients will not continue on to extended dosing.
The primary endpoints of the trial will be safety and viral load reduction on
day 15.
To expedite dose escalation, the cohort size will be reduced to
eight patients on bevirimat and two on placebo, from 12 on bevirimat and four
on placebo in the first cohort in the study. Dosing of the next cohort will be
initiated at 250 mg of the oral solution once daily, a higher dose than previously
studied in multiple-dose trials of bevirimat solution. Panacos plans to escalate
the dose in subsequent cohorts by 50 mg per cohort following review of the safety
and antiviral response from each preceding cohort. The company plans to release
data from each cohort as analysis is completed.
"We are very pleased
to continue dose escalation in our Phase 2b clinical trial," said Alan W.
Dunton, MD, Panacos' Chief Executive Officer. "While we saw several patients
with antiviral responses in the first Phase 2b cohort, we believe that the 250
mg liquid dose cohort should provide substantially greater bevirimat plasma concentrations
with the potential for correspondingly greater antiviral responses. Models relating
antiviral response to drug levels based on earlier bevirimat clinical data indicated
that doses of the liquid solution in the 300-400 mg range would be likely to approach
the maximum antiviral effect. Our new study design should allow us to see antiviral
response data from that dose range later this year."
After dose escalation
to determine the optimal dose(s) of bevirimat, the company plans to dose one or
more cohorts for at least a three-month period, using an optimized formulation
suitable for pivotal clinical trials. These long-term dosing cohorts may enroll
greater numbers of patients in need of new treatment options, and the company
believes they would be the basis for demonstrating safety and efficacy prior to
initiating pivotal clinical trials of bevirimat.
Dr. Dunton commented,
"We continue to make progress on development of a formulation suitable for
extended dosing in Phase 2b and look forward to providing further updates on that
program over the next few months. Our goal is to develop an optimized formulation
for extended dosing in Phase 2b later this year. Based on this progress and the
dose escalation plan, we believe we will be able to initiate pivotal trials of
bevirimat in 2008."
03/23/07
Source Panacos
Pharmaceuticals (via Business Wire). Panacos Announces Bevirimat Phase 2b Dose
Escalation Strategy. Press release. March 12, 2007.
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Panacos
Announces Bevirimat Phase 2b Dose Escalation Strategy
