Amdoxovir plus Zidovudine Demonstrates Potent Antiviral Activity in HIV-Infected Patients
RFS Pharma Announces a 2 Log Plasma Viral Load Decline Following
10 Day Treatment with a Dual Combination of Amdoxovir (DAPD) and
Retrovir (AZT) in HIV-1 Infected Individuals
ATLANTA, GA, February 6, 2008 -- RFS Pharma, LLC, announced
positive results from a Phase 2 clinical study evaluating
Amdoxovir® (DAPD) and Retrovir® (AZT) in 24 HIV-infected
individuals. The results from this study were presented at the 15th
Conference on Retroviruses and Opportunistic Infections (CROI) held
in Boston, MA. DAPD 500 mg bid was administered alone or in
combination with AZT 200 mg or 300 mg bid for 10 days. DAPD and AZT
combination produced a 2 log viral load decline, suggesting
synergy. There was markedly decreased viral load variability with
DAPD and AZT combination compared with DAPD alone. Furthermore,
there was no significant difference in viral load decline when DAPD
was combined with AZT 200 or 300 mg bid, indicating that the two
doses of AZT in combination with DAPD were equivalent in terms of
effectiveness. Adverse events were mild to moderate and
transient.
“The results from this study are very promising and warrant
confirmation and further development of coformulated DAPD with AZT
for second line therapy,” stated Dr. Robert L. Murphy,
Professor of Medicine in the Division of Infectious Diseases at
Northwestern University and the presenting author of the
study.
“We are particularly encouraged by the consistent 2 log drop
obtained with this combination. The potency, durability and broad
resistance profile for DAPD and AZT combination will provide a
robust regimen in the HIV treatment armamentarium,” said
Nancy Kivel, MD, Chief Medical Officer of RFS Pharma.
DAPD plus AZT 200 mg was significantly more potent compared with
DAPD alone (p < 0.04), suggesting synergy. AZT 300 mg bid was
equivalent in potency to AZT 200 mg bid, when combined with DAPD.
Viral load decline was significantly improved with DAPD plus AZT
200 mg and plus AZT 300 mg compared with AZT monotherapy (p <
0.0001). There were no apparent pharmacological drug-drug
interactions observed.
Study Design
This was a Phase 2a, randomized, double-blind, placebo-controlled
20 day study evaluating the tolerability, safety, efficacy,
post-treatment effect and pharmacokinetics of DAPD and AZT.
Twenty-four subjects, who were not receiving antiretroviral therapy
and had a plasma HIV-1 RNA viral load ? 5,000 copies/ml, were
randomized to DAPD 500 mg bid/placebo, DAPD 500 mg/placebo plus AZT
200 mg bid or DAPD 500 mg/placebo plus AZT 300 mg bid administered
for 10 days. In each arm, subjects were randomized 3:1 to DAPD or
placebo. Subjects enrolled in the study had a baseline mean viral
load of 4.5 log and mean CD4+ cell count of 417 cells/mm3.
About Amdoxovir
Amdoxovir is a nucleoside analog prodrug that is metabolized to its
2’-deoxyguanosine analog, DXG, which is a potent and
selective inhibitor of HIV-1, including drug resistant viruses
harboring M184V/I and thymidine analog mutations (TAMS). Resistance
to DAPD develops slowly in MT-2 cells and is associated with K65R
or L74V. Mutations associated with DAPD resistance have not been
identified in humans. Virus containing the K65R mutation show
moderate to high cross resistance to the approved drugs,
Ziagen® (abacavir, ABC), Videx® (didanosine, ddI),
Viread® (tenofovir disoproxil fumarate, TDF) and Epivir®
(lamivudine, 3TC), but increased sensitivity to Retrovir®
(zidovudine, AZT). DAPD has been safely administered to over 200
adults in seven Phase 1 and 2 studies.
About RFS Pharma, LLC
RFS Pharma, LLC, was founded in September 2004 and is located in a
26,500 sq. ft. state-of-the-art research facility in Tucker,
Georgia. RFS Pharma is a privately owned biotech company committed
to the discovery and development of antiviral agents and other
human therapeutics. The company capitalizes on its expertise in
nucleoside chemistry to develop drugs to combat infections caused
by drug-resistant HIV and hepatitis viruses. RFS Pharma’s
lead product candidate is Amdoxovir, which is in advanced Phase 2
clinical studies for the treatment of HIV-1 infections under a US
IND. For further information about RFS Pharma, please refer to
http://www.rfspharma.com
Forward-looking Statements
“Safe Harbor" Statement: Any statements in this press release
that relate to the Companies’ expectations are
forward-looking statements, within the meaning of the US Private
Securities Litigation Reform Act of 1995. Since this information
may involve risks and uncertainties and be subject to change at any
time, the Companies’ actual results may differ materially
from expected results. The Companies disclaim any obligation to
update the statements contained in this press release.
Retrovir, Ziagen and Epivir are registered trademarks of
GlaxoSmithKline. Videx is a registered trademark of Bristol-Myers
Squibb. Viread is a registered trademark of Gilead Sciences,
Inc.
SOURCE: RFS Pharma, LLC
Posted: February 2008
