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Maturation Inhibitor PA 457 from Panacos, Dosed Orally Once Daily
and Active against Resistant Virus, Is Potential Breakthrough Drug
Treatment for HIV
Panacos
Pharmaceuticals, Inc. has announced the successful completion of
a Phase 2a clinical study of its lead HIV drug candidate, PA-457,
and provided preliminary analysis of the results. PA-457 is
the first in a new class of HIV drugs called “maturation inhibitors,” with
broad activity against HIV, including against strains resistant
to currently approved drugs. Following is an edited version of the
text of the Panacos announcement:
The Phase
II study met its primary endpoint by demonstrating a statistically
significant reduction in the level of HIV in the blood compared
to placebo. The median reduction in HIV viral load
in the trial was greater than 1 log10, or a 90% decrease, at the
highest dose. The US Food and Drug Administration (FDA) has
granted Fast Track designation to PA-457.
In this
randomized double-blind Phase 2a study, performed at leading academic
centers in the US, PA-457 at one of four doses (25, 50, 100 or 200mg;
6 patients per group) or placebo (8 patients), was administered
orally once daily for 10 days to HIV-infected subjects not on other
antiretroviral therapy. The primary endpoint was viral load reduction
on day 11. Other endpoints included safety, tolerability and
pharmacokinetics
of the drug.
At the
100 and 200 mg doses, PA-457 treatment for 10 days resulted in statistically
significant reductions in viral load compared to placebo, with individual
decreases of up to 1.7 log10.
At the
200mg dose level, the median viral load change at Day 11 was -1.03
log10. Median Day 11 values at the other dose levels were:
Placebo: +0.03 log10; 25mg: +0.05 log10; 50mg: -0.17 log10;
100mg: -0.48 log10. In patients with baseline viral loads
under 100,000 copies/ml the median Day 11 reduction was -1.52
log10 at the 200mg dose level (three of six patients) and -0.56
log10 at the 100mg dose level (five of six patients).
Genetic
analysis of HIV in patients pre- and post- treatment, available
now for 21 out of 33 patients in the study, showed no evidence of
the development of resistance to PA-457, the same result as seen
previously in a single dose study with PA-457.
All doses
were observed to be generally safe and well tolerated with no Grade
3 or 4 laboratory abnormalities. All adverse experiences
were mild or moderate and no dose-limiting toxicity was identified.
One moderate
adverse event was classified as possibly related to drug and was
categorized as serious based on the subject's hospitalization for
diagnostic tests. It involved a patient with a 5-year history
of poorly controlled hypertension who exhibited transient findings
of a possible lacunar cerebrovascular accident, a known complication
of hypertension.
Graham
P. Allaway Ph.D., Chief Operating Officer of Panacos, said: "This
study indicates that PA-457 has potent anti-HIV activity, providing
further clinical proof of principle for this new class of antiretroviral
drugs. The overall viral load reduction at the 200mg dose
of over 1 log10 strongly supports further development of PA-457.
The 1.5 log10 viral load reduction seen in patients at the 200mg
dose with less than 100,000 viral copies/ml may potentially reflect
the potency of the drug when used in combination therapy in normal
clinical practice."
Panacos
has submitted the results of this study as a late breaker abstract
to the 45th Interscience
Conference on Antimicrobial Agents and Chemotherapy
(45th ICAAC), to be held
in New Orleans, LA September 21-24, 2005. If accepted, a detailed
description of the study will be provided at that conference.
"We
are extremely pleased with the results of this important Phase 2a
study," commented Samuel K. Ackerman, MD, Chairman and CEO
of Panacos. "We believe that PA-457 is a potential breakthrough
drug which could play a role throughout the HIV treatment spectrum,
including both naïve and treatment-experienced patients, based on
once-a-day oral dosing, potent activity observed against drug resistant
virus and a promising safety profile. We now plan to move
forward aggressively to initiate a Phase 2b study of the drug in
the first half of 2006."
About
PA-457
PA-457
is a small molecule, oral HIV drug candidate. It works by
a mechanism different from that of approved drugs or other drugs
in development, by blocking a key step in the processing of a viral
core protein called capsid.
This
novel mechanism of action, called maturation inhibition, was discovered
by Panacos scientists and their collaborators. Preclinical
studies have shown that PA-457 retains full activity against drug-resistant
virus, is effective in an animal model of HIV infection and should
be suitable for use in combination therapy with other drugs.
A previous
clinical study indicated that a single oral dose of PA-457 has antiviral
activity in HIV-infected patients, including individuals infected
with drug resistant strains. Clinical results to date will
need to be confirmed and extended in longer term trials with larger
patient numbers prior to approval.
Fast
Track is a process designed to expedite development and approval
of new drugs that may have the potential to improve treatment for
serious or life-threatening diseases. Developers of Fast Tracked
products have greater access to FDA resources as well as eligibility
for rolling NDA submissions. In addition, Fast Track designation
may enable priority FDA review and accelerated approval.
About
Panacos Pharmaceuticals
Panacos,
formerly known as V. I. Technologies, Inc. or VITEX, 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. Panacos's proprietary
discovery technologies and lead therapeutic candidate PA-457 focus
on novel targets in the virus life cycle, including virus fusion
and virus maturation. For more information on Panacos, visit http://www.panacos.com
Articles on PA-457
New
Anti-HIV Therapies from Existing and Novel Drug Classes
-
3/07/05
FDA Grants Fast-Track
Review Status to PA-457, First in a New Class of Anti-HIV
Drugs -
2/14/05
New
Anti-HIV Drug Candidate PA-457 Exhibits Potent Anti-HIV Activity
Following a Single Dose in HIV Patients
-
12/06/04
Maturation
Inhibitor PA-457 Is a Potent Experimental Drug in a New Class
of Anti-HIV Compounds
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12/06/04
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