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Safety, Tolerability and Activity of KP-1461 a Novel Viral Mutagen in HIV Infected Adults
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Reported by Jules Levin
9th International Workshop on Clinical Pharmacology of HIV Therapy
April 7, 2008
New Orleans, Louisiana
PG Clay (1), MP McRae (1), DE Sweet (2), OO Osiyemi (3), E Godofsky (4), RE Redfield (5), SE Smith (6), R Campo (7), J Shrank (8), J Parkins (9), S Becker (9)
1 - Kansas City University of Medicine and Biosciences, Kansas City, MO; 2 - University of Kansas School of Medicine-Wichita, KS; 3 - Triple O Medical Services, West Palm Beach, FL; 4 - Bach and Godofsky, MD, PC, Sarasota, FL; 5 - University of Maryland, Baltimore, MD; 6 - New Jersey Medical School, Newark, NJ; 7 - University of Miami, Miami, FL; 8 - Greenville Hospital System, Greenville, SC; 9 - Koronis Pharmaceuticals, Inc., Redmond, WA
BACKGROUND
KP-1461 is an oral prodrug of KP-1212, which in vitro irreversibly extinguishes HIV through the process of Viral Decay Acceleration
--deoxycytidine analog which as a selective viral mutagen induces base pairing errors
--In vitro leads to a progressive reduction of viral fitness, eventual error catastrophe and resultant population collapse.
KP-1461 contains an unmodified sugar, allowing continual chain elongation by RT, with a modified base that appears ambiguous to the complementary base.
Through a tautomeric process, KP-1461 can pair with either guanosine or adenosine to create G-to-A and C-to-T errors
--Base pairing errors are incorporated randomly throughout the viral genome & errors persist through subsequent replication cycles
Author Conclusion
Sufficient evidence to complete all cohorts
Phase 2 studies ongoing at this time:
An Open-Label, Multicenter, Mechanism Validation Study to Evaluate the Safety, Efficacy and Tolerability of KP-1461 as Monotherapy for 124 Days in Antiretroviral-Experienced, HIV-1-Infected Subjects (NCT00504452) (n=32)
--26 subjects enrolled,
--9 completed
--1 underwent FDA-compassionate use (beyond 124 days)
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