To: Easy Mark who wrote (342 ) 4/3/1998 1:13:00 PM From: Easy Mark Read Replies (1) | Respond to
Is this week's NEJM editorial positive or negative for Remune? The NEJM published data showing overwhelming benefits due to triple drug therapy. This has to be considered the overwhelming therapy of choice. However, they report that 1) up to 50% of patients are not responsive, 2) the therapy has severe side effects, and 3) the therapy does not eliminate HIV from hidden reservoirs. In the same issue, an editorial ratifies the use of triple drug therapy while calling for more research on these remaining issues. I believe this puts FDA in a genuine ethical dilemma. If triple drug therapy has such dramatic impact on both HIV load and on clinical end-points it seems unethical to continue clinical trials such as Remune's Phase III trial in which people are getting either placebos or Remune alone. The only pathway to remove this dilemma is to offer all patients in any HIV clinical trial the verified benefits of triple drug therapy if they choose. However, this pathway destroys the statistical relevance of the clinical trials, which are necessary to attack the remaining problems with HIV. Initially, I thought this was a negative for Remune. However, I now believe its a positive factor. My reasoning follows. It seems increasingly likely to me that the Phase III trial would need to be unblinded for ethical reasons - not because of Remune but because of the other therapies available. However, Remune is safe and has apparent (in Phase 1 and 2 studies) benefits both to patients already taking triple drug therapy, and to patients who cannot tolerate those therapies. If the interim data analysis does not contradict the early Remune results, then it would be unethical for FDA to deny patients the benefits of Remune. In other words, multiple tools are necessary for the HIV caregiver, and Remune should be in the toolkit. The only scenario that I can see to support putting Remune back to Phase II is if the interim data show some harmful effect of Remune in combination with the drugs or if the use of the therapy would prevent the use of a more beneficial therapy. Neither seems likely. An intriguing connection was revealed by the authors of the NEJM editorial. One of the authors is from University Hospital in Laussanne Swithzerland, which is, I believe the same hospital that started a combined Remune/triple drug trial in January (i.e. while the NEJM article and editorial must have been in preparation). This would seem to me to put Remune on track for potential approval when the results of current Phase II studies show that Remune can be safely given in combination with triple drug therapy i.e. by the end of 1998. This scenario is supported by my earlier observation, that FDA can approve the use of therapy with narrow restrictions e.g. to use in situations where other therapies are not appropriate. Any comments?
