REMUNE Trial Will Stop; New Trials Planned
The REMUNE(tm) HIV immunogen--the HIV treatment vaccine developed by the late Dr. Jonas Salk--is being tested in a large (2,500 volunteer) clinical-endpoint trial--meaning that this trial is looking for statistically significant differences in AIDS-related sickness or death between those who add REMUNE to their ongoing antiretroviral treatment, vs. those who add a placebo to their treatment. The REMUNE (or placebo) injections are given once every three months. The Immune Response Corporation is conducting this trial, with support from Agouron Pharmaceuticals.On May 17, the companies announced that the trial would end, after an analysis by the Data Safety Monitoring Board (DSMB), which found that differences in clinical endpoints were not observed and that the trial was unlikely to find statistically significant differences if it proceeded. There were far fewer clinical endpoints than expected when the trial was designed--apparently because of the use of modern antiretroviral therapies--illustrating the great difficulty of conducting clinical-endpoint trials of HIV therapies today. The companies did find a statistically significant difference in viral load at 48 and 96 weeks, in a randomly pre-selected cohort of 250 volunteers, only one tenth of the entire study--showing how much more efficiently a trial can be conducted with viral load, than with clinical endpoints. Viral load data may be analyzed for all the volunteers in the study; results may be presented as early as the ICAAC conference (Interscience Conference on Antimicrobial Agents and Chemotherapy, September 26-29, 1999, in San Francisco).
The companies also announced that they are planning two new phase III trials using viral load, after an agreement with the FDA that such trials could be a basis for marketing approval. (The current surrogate-marker trial happened because when it was designed, the FDA had a policy of requiring clinical-endpoint proof for immune-based therapies--a standard which today is usually prohibitive in the U.S. or other countries where modern HIV treatment is available.) Besides the low number of endpoints, this trial may also have been impacted by the fact that volunteers could use whatever treatments they wanted, monitor their viral loads, and change treatments whenever they wanted; the few endpoints which did exist might largely have represented random "noise." It is too early to make conclusions until the data have been collected and analyzed.
As this article goes to press (a day after the May 17 announcement), the companies have not decided what arrangements will be made for persons in the trial who want to continue their REMUNE treatment (or switch to the active drug, if they have been receiving the placebo). Because the DSMB secretly unblinds the trial and says nothing about its findings unless it decides that the trial should be stopped, no one including the companies knew ahead of time what the result of its recent meeting would be.
