Hello Doc Frascino,

Do you think that all the studies presented at the meetings about KP-1461 are completely false or without legs?

It is really strange to discover nearly close to the end of phase 2 humans trial that KP-1461 has no anti-hiv activity in vitro... It is bizzare, makes no sense...

Hello,

The results of the initial very promising preclinical trials as well as the very disappointing results from the phase 2 trials that were recently halted are being reevaluated. Additional information should be forthcoming within a few months. No one will be able to answer your questions until we know a bit more about what went wrong versus what went right. Stay tuned; we'll keep you informed as this story unfolds. (See below.)

Dr. Bob

KP-1461 Trial Stopped Jun 18, 2008

Novel HIV therapy suffers stunning setback by Paul Dalton, June 12, 2008

In a stunning setback, Project Inform has learned Koronis Pharmaceuticals has stopped the only ongoing study of their experimental drug, KP-1461. This decision was based on unexpected results from lab tests and not on safety concerns. Those participating in these studies have been told of these developments.

The lab tests that led to this decision were required by the FDA and were essentially repeats of earlier work done by the company. The tests, called serial passage experiments, exposed HIV to different concentrations of the drug to try and force HIV to grow resistant to it. This helps doctors and researchers understand what changes HIV creates to become resistant. Earlier tests failed to force resistance to KP-1461, so the FDA required Koronis to repeat them until resistance emerged.

The experiments were done by the same team who performed the earlier work. Surprisingly, they found that KP-1461 didnt show measurable anti-HIV activity, which conflicts with what was seen in earlier lab study. The company then looked at the results from the ongoing study and found similar results: few people experienced significant reductions in their HIV levels.

Had the results from the clinical study shown that the drug was reducing HIV levels then that would have likely trumped the laboratory finding. Instead, the review of these results confirmed the troubling results, which led to the decision to halt the study.

Only two people were taking KP-1461 at the time of this discovery. The company informed them of the findings, stopped the KP-1461, and recommended they start a full HIV regimen.

Stephen Becker MD, the lead investigator for Koronis, told Project Inform that the company is, committed to understanding these discordant results and will attempt to validate the original 2002 research, on KP-1461. Dr. Becker estimated that it would take at least two months to fully investigate this setback.

KP-1461 is a novel HIV treatment that is supposed to work by speeding up the mutation rate of HIV. In theory, this would lead HIV to mutate so much that it becomes unable to infect cells and replicate. This approach, called terminal mutagenesis,was supported by lab experiments which showed that when HIV was exposed to KP-1461 it eventually mutated itself to death. Many people were skeptical and questioned the wisdom of encouraging HIV to mutate something every other HIV drug seeks to avoid. Even those who support its development, including Project Inform, have acknowledged the unique hurdles faced by KP-1461 and Koronis.

This setback comes at a time when the pipeline of experimental HIV treatments is drying up. While the past few years have marked an impressive period for new HIV drugs, the next few look thin at best. These disappointing and unexplained results make this situation worse. Project Inform hopes that Koronis can get to the bottom of this vexing mystery and refocus its efforts on developing new treatments against HIV/AIDS.

I don't understand why they would stop this. I never once thought you would take KP-1461 for a couple months and magically be cured of HIV. I thought it would take years of using this drug and eventually it would work. It doesn't try to stop replecation; it tries to speed it up and induce errors. So why would they think taking it for a couple months would induce enough errors to cure you? I would think it would take years and now they just stop it. This was the drug that gave me hope, and now there's nothing to look forward to. Anyway I'm really wondering what you think about this Dr. Bob and I truly appreciate you taking your time to answer people's questions I love people who help others and I want to thank you so much. God bless you http://www.projectinform.org/news/2008/061208.shtml

Response from Dr. Frascino

Hello,

This news is hot off the press and I do not have any additional details other than what was reported in the Project Inform story.

Certainly Koronis will be evaluating why the two sets of results were so different. Dr. Becker hopes to have this ironed out by the time of the World AIDS Conference in Mexico City in August. Stay tuned. We'll keep you posted as the story unfolds. However, this setback is only one of many that we've had over the past quarter century as we've tried to develop effective medications and vaccines to combat HIV. It's another demonstration why we advise folks not to get overly enthusiastic about new drugs or novel therapies early in the course of their development. We've all been burned before!

Dr. Bob