Panacos Presents Bevirimat Patient Response Predictors at the International HIV Drug Resistance Workshop
WATERTOWN, Mass.--(Business Wire)--
Panacos Pharmaceuticals, Inc. (NASDAQ:PANC), today announced
factors that predict treatment response to bevirimat, a novel, oral
HIV maturation inhibitor. The findings were described during multiple
presentations at the 17th International HIV Drug Resistance Workshop
in Sitges, Spain, considered the leading conference on HIV drug
resistance. Aggregate data from Panacos' recent Phase 2b clinical
study in heavily treatment-experienced patients demonstrated that
functional monotherapy with bevirimat resulted in a mean viral load
reduction of 1.26 log 10 in patients who had these response predictors
and a threshold bevirimat concentration of 20 ug/mL.
The predictors of response to bevirimat are located at three codon
positions on the 500-amino acid HIV-1 Gag protein. Bevirimat
specifically blocks a late step in processing of Gag, leading to the
production of virus particles that are structurally defective and are
incapable of spreading infection around the body. Patients who have
virus with the most commonly occurring amino acids at positions 369,
370 or 371 on Gag are much more likely to respond to bevirimat
treatment. In contrast, those patients whose virus has polymorphisms
(variants) at these positions are less likely to respond to the drug.
These retrospective clinical data have been confirmed by multiple
laboratory analyses and currently are being tested in a prospective
clinical trial in treatment-experienced and treatment-naive HIV
patients.
Any change in the amino acid sequence of Gag may be determined
easily with a simple and rapid genotype assay, the type of HIV
resistance test most frequently ordered by HIV-treating clinicians.
The frequency of Gag polymorphisms is variable depending on the
population tested. In one survey of an academic patient database in
North America, polymorphisms at Gag positions 369, 370, or 371 were
absent in 60.2% of 567 treatment-naive patients. A 2007 publication
from multiple HIV clinics in France demonstrated that approximately
68% of samples from 82 protease inhibitor-experienced patients were
free of these same Gag polymorphisms (Malet, et al, AIDS 2007, Vol 21,
No 7:871-3). Patients without these Gag polymorphisms would be ideal
candidates for bevirimat treatment.
Dr. Alan W. Dunton, Panacos' President and CEO, stated,
"Identifying the specific predictors of treatment response to
bevirimat is an important advance. These significant results--in such
heavily treatment-experienced patients-- should allow us to design
bevirimat trials in a way to maximize the chance of a treatment
response. These pioneering data are being incorporated into our
clinical programs and the design of our Phase 3 registration studies
for this first-in-class novel mechanism compound."
In the Phase 2b study, which forms the basis for the
presentations, 44 heavily treatment-experienced patients were given
bevirimat for 14 days as functional monotherapy in escalating dose
groups. Baseline clinical and virological variables were assessed to
establish the determinants of bevirimat response. Response was also
correlated with the baseline HIV Gag amino acid sequence.
The clinical data on bevirimat patient response predictors were
presented in the following session at the International HIV Drug
Resistance Workshop:
June 11, 2008, 11:45 AM; Location: Melia Sitges
ORAL PRESENTATION, Abstract Title: HIV-1 Gag Polymorphisms
Determine Treatment Response to Bevirimat (PA-457)
Contributing authors: S. McCallister, J. Lalezari, G. Richmond, M.
Thompson, R. Harrigan, D. Martin, K. Salzwedel, G. Allaway
Three additional poster presentations at the Resistance Workshop
described studies confirming the role of Gag polymorphisms on
bevirimat activity. The first was a collaborative study between
Panacos scientists and Dr. Eric Freed's laboratory at the National
Cancer Institute, Frederick, MD.
Abstract Title: Role of Gag Polymorphisms in HIV-1 Sensitivity to
the Maturation Inhibitor Bevirimat
Contributing authors: K. Salzwedel, M. Reddick, C. Matallana, C.
Finnegan, C. Adamson, M. Sakalian, D. Stanley, E. Freed, G. Allaway
In this study, the researchers generated HIV-1 bearing
polymorphisms in the Gag SP1 peptide, adjacent to bevirimat's target
at the capsid (CA)-SP1 junction, by point mutation or construction of
chimeric viruses containing CA-SP1 regions from bevirimat-treated
patients. Viruses containing deletions, substitutions or naturally
occurring polymorphisms at Gag positions 369, 370 and 371 in SP1
displayed reduced sensitivity to bevirimat in viral replication assays
as well as in assays of the inhibition of CA-SP1 cleavage by
bevirimat.
A second study was presented by scientists at InPheno AG, Basel,
Switzerland in collaboration with Panacos.
Abstract Title: New Phenotyping Assay Demonstrates Role of Gag-SP1
Polymorphisms in HIV-1 Sensitivity to the Maturation Inhibitor
Bevirimat
Contributing authors: F. Hamy, S. Louvel, K. Salzwedel, T.
Klimkait
In this study, a high throughput phenotyping assay was used to
assess susceptibility to bevirimat using clinical virus samples. The
level of in vitro sensitivity was closely related to the presence or
absence of polymorphisms at Gag residues 369/370/371, supporting the
clinical correlations that have been observed.
The third poster was presented by Virco BVBA, Mechelen, Belgium in
collaboration with Panacos.
Abstract Title: HIV-1 Susceptibility to the Maturation Inhibitor
Bevirimat is Modulated by Natural Polymorphisms at Positions 369-371
in Gag SP1
Contributing authors: K. Van Baelen, K. Salzwedel, J. De Wolf, Y.
Verlinden, L.J. Stuyver
In this study, phenotypic and genotypic assays were used to
establish three levels of susceptibility to bevirimat for a set of 20
patient-derived virus isolates. Reduced susceptibility correlated with
polymorphisms of Gag residues 369-371 in SP1.
Panacos' Development Programs
Panacos' lead compound, bevirimat (PA-457), is the first in the
new class of HIV drugs under development called maturation inhibitors,
discovered by Company scientists and their academic collaborators.
Bevirimat is designed to have potent activity against a broad range of
HIV strains, and studies have shown bevirimat is a potent inhibitor of
HIV isolates that are resistant to currently approved drugs. Panacos
has completed 11 clinical studies of bevirimat in over 485 patients
and healthy volunteers, showing significant reductions in viral load
in HIV-infected patients and a promising safety profile, and is
currently in Phase 2b clinical trials.
In addition to bevirimat, the Company has a second-generation
program in HIV maturation inhibition and has selected a lead compound
for preclinical development in its oral HIV fusion inhibitor program.
The new understanding of the role of Gag polymorphisms in maturation
inhibitor activity is unique to Panacos and the Company is building a
strong intellectual property position around its important discovery.
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.
Approximately 1 million people in the United States and approximately
33 million people worldwide are living with HIV. Approximately 475,000
patients are treated annually for HIV in the United States. 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.
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,
2007. 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.
Panacos Pharmaceuticals, Inc.
Jane Pritchett Henderson, 617-926-1551
Chief Financial and Business Officer
Copyright Business Wire 2008
