Tobira's Next-Generation Once-Daily CCR5/CCR2 Antagonist Demonstrates Potent CCR2 Inhibition, Antiviral Activity, Safety and Tolerability in Treatment-Experienced Patients With HIV
TBR-652 Phase IIa Data Presented at XVIII International AIDS Conference Showcase Potentially Important Anti-Inflammatory Benefits
VIENNA, July 19 /PRNewswire/ -- Phase II data for TBR-652, a
novel compound being developed by Tobira Therapeutics for the
treatment of HIV infection, demonstrate that the dual CCR5/CCR2
antagonist provides potent antiviral activity and inhibition of the
CCR2 receptor and is generally safe and well-tolerated in
treatment-experienced patients with HIV. The data were presented
here today in an oral presentation at the XVIII International AIDS
Conference.
In a Phase IIa trial involving 54 patients, a 10-day course of
once-daily TBR-652 monotherapy produced a median nadir decline from
baseline in HIV viral load of up to 1.8 log10 copies/mL. There were
no serious adverse events, deaths or study drug-related
discontinuations in the proof-of-concept study. Investigators also
observed dose-dependent changes in concentrations of monocyte
chemoattractant protein-1 (MCP-1), the primary ligand for the CCR2
chemokine receptor and a potent chemoattractant for monocytes and
macrophages. This latter finding provides further evidence of
TBR-652's dual action on CCR5 and CCR2, suggesting a potential
anti-inflammatory benefit of the compound. Importantly, to date, no
significant safety signals have been identified with CCR2
antagonists.
"This study of TBR-652 showed a statistically significant,
dose-dependent effect on MCP-1 levels -- an important biomarker for
CCR2 activity," observed David E. Martin, Pharm.D., Senior Vice
President, Drug Development/Regulatory Affairs, Tobira
Therapeutics, Inc. "The potential anti-inflammatory benefits of
this dual CCR5/CCR2 antagonist will be further investigated in a
series of Phase IIb sub-studies to evaluate the effects of TBR-652
on immunologic and inflammatory parameters, including
cardiovascular and metabolic endpoints."
Dr. Martin presented data from Study 652-2-201, a double-blind,
placebo-controlled, dose-escalation trial in which patients were
randomized four-to-one to receive doses of TBR-652 of 25mg, 50mg,
75mg, 100mg, 150mg and placebo.
All patients were HIV treatment-experienced, though none had
previously been treated with a CCR5 antagonist. Most adverse events
in the study were mild in severity (Grade 1). There were no
clinically significant trends in adverse events, laboratory tests,
vital signs, or electrocardiogram measurements. Additionally, there
were no liver function test elevations greater than Grade 1.
The following dose-escalation chart outlines the antiviral
activity (as evidenced by reductions in HIV viral load) and
inflammation-marker change (as evidenced by increases in MCP-1
levels) of TBR-652:
Dosing HIV-1 RNA: median
cohort nadir MCP-1: mean change
change from from baseline after
baseline 10
(log10 copies/mL) days (pg/mL)
25 mg -0.7* +56.3
50 mg -1.7** +94.2(**)
75 mg -1.8** +34.4
100 mg -1.4** +92.7(**)
150 mg -1.7** +334.3(**)
------ ------ --------
placebo -0.3 -1.9
------- ---- ----
*P=0.002 vs. placebo; **P<0.001 vs. placebo; (**)P less than or equal
to 0.02 vs. placebo
Dr. Martin described the dose-dependent increase in MCP-1
concentrations as a promising development, as was the favorable and
predictable pharmacokinetic profile observed with TBR-652. "Our
unique, dual CCR5/CCR2 investigational drug may provide a new
strategy that would complement the well-established benefits of
currently available virus-suppressing treatments for HIV," Dr.
Martin said.
"Chronic inflammation increases the risks of cardiovascular
disease, neurocognitive deficits, age-related disorders and
non-AIDS-defining malignancies. These events account for nearly
half of deaths in HIV-infected patients," said Kathleen Squires,
M.D., Professor of Medicine, Director, Division of Infectious
Diseases at Jefferson Medical College. "The development of a novel,
combination antiretroviral agent that is safe, tolerable, potent
and can modulate the chronic inflammation associated with HIV could
have a powerful impact on improving and extending lives of people
with HIV," she added.
About Tobira Therapeutics, Inc.
Tobira Therapeutics is a private biopharmaceutical company which
is focused on developing and commercializing innovative antiviral
compounds to treat HIV disease. The company was founded in 2006 by
Eckard Weber, M.D., a partner at Domain Associates, to develop
novel treatments for HIV disease. Tobira has assembled a highly
experienced management team with decades of clinical and commercial
development experience specifically in HIV/AIDS drug
development.
www.tobiratherapeutics.com
Source: Tobira Therapeutics, Inc.
CONTACT: John F. Kouten of JFK Communications, Inc. for
Tobira
Therapeutics, +1-609-514-5117, Cell, +1-908-227-4714, jfkouten@jfkhealth.com;
or Susan Wolfson of Tobira Therapeutics, Cell,
+1-917-340-8089,
swolfson@tobiratherapeutics.com
Web Site: http://www.tobiratherapeutics.com/
Posted: July 2010
