Koronis' KP-1461 drug causes extra mutations to occur in HIV genome in HIV-infected patients

Recently published Phase 2a clinical trial results show that the frequency of specific, drug-induced mutations in the HIV genome can be significantly increased by administering KP-1461, a drug being developed by Koronis Pharmaceuticals based on its novel Viral Decay Acceleration (VDA) drug mechanism. Koronis is planning a follow-on Phase 2 trial to determine the treatment duration required to achieve a clinically meaningful decrease in a patient's viral load.

"These clinical findings confirm that KP-1461 causes extra mutations to occur in the HIV genome in HIV-infected patients. We believe the accumulation of extra mutations will eventually cause a critical loss of fitness in a patient's HIV population. If clinical results from a longer trial confirm that loss of fitness can reduce a patient's viral load to a clinically meaningful degree, then we believe VDA will become a viable mechanism for an entirely new class of non-suppressive HIV therapeutics", said lead author James Mullins, Ph.D., Professor of Microbiology and Medicine at the University of Washington.

All approved HIV therapeutics employ suppressive drug mechanisms that inhibit viral enzymatic functions, or block the entry of the virus into uninfected cells. Currently, these suppressive drugs must be administered in a multi-drug cocktail to minimize emergence of drug-resistant HIV strains, and require lifelong administration to ensure continuous suppression of viral replication.

If durable reductions in patient viral populations can be demonstrated in future trials, VDA would become the first clinically-demonstrated non-suppressive drug mechanism against HIV. The possibility of using a non-suppressive drug mechanism such as VDA in HIV treatment would have significant implications for treatment paradigms and could lead to a much wider distribution of anti-HIV drugs throughout the world.

"These results indicate that KP-1461 can increase the frequency of mutations in HIV-1 populations. Importantly, it also appears to be generally safe and well tolerated based on results from the more than 80 patients who have received the drug. While larger studies are obviously needed, the conclusions from this paper certainly underscore the potential for positive clinical effects. This should encourage further development of the VDA mechanism as a new approach for the treatment of HIV-1 infection," said Charles Hicks, MD, Professor of Medicine at Duke University Medical Center, who is also Director of the Duke University Interdisciplinary Research Training Program in AIDS.

The recently published paper appears in the January 14, 2011 PLoS One Journal, an international, peer-reviewed publication produced by the Public Library of Science, and presents an analysis of HIV-1 gene sequences from heavily treatment-experienced HIV-infected volunteers treated with KP-1461 for a 4-month period.