Message #19 From:
NewsBot Date: December 19, 2006 01:02:00 PM
PANC News Panacos Announces First Cohort Results of Phase 2b Study
WATERTOWN, Mass.--(BUSINESS WIRE)--Panacos Pharmaceuticals, Inc. (Nasdaq:PANC), a biotechnology company
dedicated to developing the next generation of antiviral therapeutic
products, today announced preliminary results from the first cohort of a
Phase 2b study of bevirimat (PA-457) in patients failing HIV therapy due
to drug resistance. The data confirm the clinical antiviral activity of
bevirimat shown in previous studies; however, the bevirimat plasma
concentrations were lower than anticipated, suggesting that the tablet
formulation used for this study did not deliver the drug as expected.
After 14 days of dosing with 400 mg of bevirimat tablets administered on
top of patients’ failing background regimens,
an antiviral effect was seen in the bevirimat treatment group. Two out
of twelve patients with multiple-drug-resistant HIV who received
bevirimat achieved an undetectable level of virus. These two patients
and one other individual had a viral load reduction of greater than 1
log10. However, the overall antiviral response in this first cohort was
less than expected, in line with the patients' lower than anticipated
bevirimat plasma concentrations. A previous bioavailability study had
predicted that the plasma concentrations, and therefore the antiviral
response, of the 400 mg tablet dose would be comparable to the highest
(200 mg) dose of the oral solution used in the Phase 2a study. Instead,
both the plasma concentrations and the antiviral response observed in
the 400 mg tablet cohort were similar to the 100 mg Phase 2a oral
solution dose. The data suggest that the lower plasma concentrations of
drug resulted from the properties of the 50 mg tablet, a prototype
designed specifically for use in the Phase 2b trial. Panacos has been
working for some time on new tablet formulations for late-stage
development and commercialization. Preliminary analysis of the safety
profile of bevirimat in the first cohort indicated that bevirimat was
generally safe and well tolerated.
Graham Allaway, Panacos' President and COO said, “While
this first cohort did not produce the bevirimat levels we had hoped for,
we were encouraged that some patients exhibited a very good antiviral
response. Overall, the data are consistent with the relationship between
plasma concentrations and response that we have seen previously, and we
believe the results support going to higher doses, potentially with
alternative formulations, with the aim of generating greater responses.
We are submitting a proposal to the FDA designed to continue bevirimat
dose escalation in Phase 2b as soon as possible while we continue to
develop an optimized formulation of bevirimat for commercialization.”
First Cohort Results
The initial Phase 2b bevirimat tablet dose of 400 mg was chosen based on
an earlier clinical bioavailability study indicating that the tablet had
approximately 60% of the oral bioavailability of an oral solution
formulation. As a result, this 400 mg tablet dose was expected to be
comparable to a 200 mg oral solution dose, which in a 10 day bevirimat
Phase 2a monotherapy study had generated a median 1 log10 viral load
reduction. However, analysis of bevirimat plasma levels in this Phase 2b
study found that these levels were about half what was expected and
closer to levels that were seen in patients using 100 mg of oral
solution in the earlier Phase 2a study.
Consistent with these lower drug plasma concentrations, the antiviral
responses seen in the 400 mg tablet cohort of the Phase 2b study were
also lower than expected. At day 15, the mean viral load reduction was
0.36 log10 in bevirimat-treated patients compared to 0.02 log10
reduction in placebo-treated patients. A total of three patients on
bevirimat had greater than 1 log10 reduction in viral load and continued
on to the extended dosing portion of the study, including two who
achieved an undetectable level of virus (<400
viral copies/ml). One additional patient who had a viral load change of
just under 1 log10 on day 15 was continued on therapy by special
investigator request.
During the initial 15 day dosing period, there were no reports of
drug-related serious adverse events or withdrawals due to adverse
events. One patient on bevirimat withdrew after 12 days for reasons not
related to the drug. A day 15 viral load sample was obtained from that
patient and the patient was not replaced. These data continue to confirm
the good safety and tolerability profile of bevirimat found in previous
studies.
Given the similar bevirimat plasma concentrations seen in the Phase 2b
400 mg tablet cohort and the 100 mg oral solution cohort in the Phase 2a
study, the viral load changes in the two studies were compared. The mean
viral load changes on day 11, the appropriate comparator time point,
were -0.39 log10 and -0.37 log10 in the current study and the Phase 2a
100mg cohort respectively. In the current study, four of the twelve
patients (33%) had a greater than 0.5 log10 reduction in viral load on
day 11, and three of these had a greater than a 1 log10 reduction. In
the 100 mg liquid dose cohort of the prior Phase 2a study, three of six
(50%) had greater than a 0.5 log10 viral load reduction, and no patients
had greater than a 1 log10 reduction.
About the Phase 2b Bevirimat Study
The objectives of the Phase 2b study of bevirimat are to examine the
antiviral efficacy, pharmacokinetics, and safety of bevirimat in
combination with other HIV drugs. In this study, HIV-infected patients
failing their current therapies due to drug resistance are treated with
bevirimat (12 patients) or placebo (4 patients) on top of their failing
background drug regimen for 14 days, a period of “functional
monotherapy.” At the end of this period their
background drug regimen is optimized for antiviral activity based on
each patient’s individual viral resistance
profile, continuing with bevirimat or placebo treatment in addition to
this new background regimen for an extended dosing period of ten weeks.
Under the protocol for the trial, patients receiving bevirimat are
required to have greater than a 1 log10 reduction in viral load on day
15 to continue on to this optimized background portion of the study. The
study has a dose escalation design with the initial cohort having been
treated with 400 mg bevirimat in tablet form.
Conference Call Participation Details
The Company will host a conference call to discuss these results at 5:00
p.m. today (EST). The conference call can be accessed via the web at www.panacos.com
or by dialing (866) 700-6293 (domestic) or (617) 213-8835
(international), between 4:45 and 4:55 p.m. and entering the passcode
11391629. A replay of the conference call will be available from 7:00
p.m. on December 19, 2006 until Thursday, January 18, 2007, and can be
accessed via the web at www.panacos.com
or by dialing toll-free (888) 286-8010, and outside the U.S. (617)
801-6888 with passcode 99545652.
About Panacos
Panacos is developing the next generation of anti-infective products
through discovery and development of small molecule oral drugs for the
treatment of HIV and other major human viral diseases. HIV infects
approximately 1.7 million people in North America and Western Europe and
approximately 40 million people worldwide. Approximately 650,000
patients are treated annually for HIV in the United States and Western
Europe. Resistance to currently available drugs is one of the most
pressing problems in HIV therapy and the leading cause of treatment
failure. Panacos' proprietary discovery technologies are designed to
combat resistance by focusing on novel targets in the virus life cycle,
including virus maturation and virus fusion.
Panacos' lead candidate, bevirimat (PA-457), is the first in a new class
of oral HIV therapeutics under development called maturation inhibitors,
discovered by Panacos scientists and their academic collaborators. Based
on its novel mechanism of action, bevirimat is designed to have potent
activity against a broad range of HIV, including strains that are
resistant to existing classes of drugs. The Company has completed seven
clinical studies of bevirimat in over 300 subjects, showing significant
reductions in viral load in HIV-infected subjects and a promising safety
profile, and is currently in Phase 2b clinical trials.
Except for the historical information contained herein, statements
made herein, including those relating to bevirimat's clinical
development, the potential results of treatment with bevirimat, and
future clinical trials and clinical practice, are forward-looking
statements made pursuant to the safe harbor provisions of the Private
Securities Litigation Reform Act of 1995. These statements involve risks
as set forth in the Company's filings with the Securities and Exchange
Commission, including, but not limited to, the Company's Annual Report
on Form 10-K for the fiscal year ended December 31, 2005. These risks
and uncertainties could cause actual results to differ materially from
any forward-looking statements made herein. The Company undertakes no
obligation to publicly update forward-looking statements, whether
because of new information, future events or otherwise, except as
required by applicable law.
