Advanced Viral Research Corporation Waits for Results of AVR118's Cachexia Trial

By Chael Needle

LifeGuide

[Treatment Horizons]

Advanced Viral Research Corporation (ADVR) has released a forward-looking preliminary sketch of forthcoming results of a clinical trial in Israel studying the safety of AVR118 (formerly called Product R), an immunomodulator, in its treatment of body wasting. The results have not been published yet and cannot be reviewed, but ADVR decided to send out a press release claiming that the first fifteen patients in the study, all of whom were experiencing body wasting as well as failing HAART regimens, showed improvement in appetite, weight gain or stability, and enhanced quality of life; none reported significant side effects. Readers should note the smallness of the sample—not because it’s unusual for a Phase I trial, but because it’s too early to tell if these results can be replicated and if the other fifteen patients that will complete the results will make good on the theorized safety and efficacy. The only FDA-approved treatment for body wasting in individuals with HIV/AIDS so far is the recombinant human growth hormone, somatropin.

I had interviewed Dr. Shalom Z. Hirschman, then-President and CEO of ADVR, in November 2002 for this column. At the time, Dr. Hirschman was excited about the Israeli studies, which would look at the immunomodulator as a possible salvage therapy for patients failing HAART, as well as a treatment that could reverse body wasting and mitigate the toxicities of HAART drugs. I was expecting to hear results about AVR118 as a salvage-therapy candidate. As it turns out, the only results offered so far concern body wasting. An important quality-of-life issue, to be sure, but the absence of news about other trial goals is disappointing.

“When we looked the raw data that was published—or, rather, put out into the press release—what we found was that virtually every patient had a response. In other words, all patients had a response, “ says Dr. James D’Olimpio, M.D., Director of the North Shore University Hospital’s Supportive Oncology and Palliative Care Service in Manhasset New York, and a member of ADVR’s Scientific Advisory Board as well the company’s spokesperson. “All fifteen patients responded in the kind of parameters [one needs] to publish with. I can’t get into that right now because the database isn’t complete.” Though he is not participating as a researcher in the trial, he has treated body wasting in patients with cancer as well as those with HIV/AIDS since the mid-eighties and has researched body wasting for the past five years. He sees this trial as part of new scientific attention being devoted to understanding body wasting. Any drug that is eventually developed, however, won’t be a “magic bullet, or monotherapy. It’s going to be a number of things. We’re building pieces of the puzzle,” he says. “AVR118 could be something we can use to reverse the process of body wasting.”

Dr. D’Olimpio has found that treating body wasting, or cachexia, in patients with cancer dovetails with patients with HIV disease. Body wasting is caused by different things in each but they do have similar models in the sense that “both have a number of different inflammatory pathways that become activated” in common.   Says Dr. D’Olimpio: “The key feature in both situations is that skeletal muscle, what’s called lean body mass, is significantly affected. Once skeletal muscle is affected, then the body cannot fight it off from the standpoint of immune response or from the standpoint of being able to tolerate therapy.” The organs cannot support themselves as a result and eventually deteriorate, he says, as evidenced by the “20,000 individuals who ultimately die of HIV disease each year who lose weight as the key feature of why they get infections or why infections lead to weight loss.” He continues: “The weight loss itself is a reflection of this inflammatory process by which patients cannot muster an effective response and/or tolerate their treatments.”

One present goal for treatment research in general is to find drugs that down-regulate or interrupt these pathways. The targets are the signals that tell the body to siphon off protein from muscle and, in effect, keep aberrant inflammatory processes going. EPA, a fatty acid, and amino acids have been found to dampen signals, according to D’Olimpio. “It also seems that AVR118 does this. The information coming out is worthy of scientific publication.” At this point, however, all we can do is wait and see if a new treatment for body wasting is indeed on the way.

Chael Needle reported on cardiovascular disease and HIV for the December 2003 issue.

January 2004