There is a highly credible report that the Forum Pharmaceuticals Phase III trials for encenicline/FRM-6124 are being halted due to a safety issue: Gastric hypomotility setting the stage for eventual gut perforation. FRM-6124 is a program that NIR has long followed, and while there have been questions raised regarding the magnitude of its procognitive impact, we have seen it as one of the more promising options for cognition in Alzheimer’s and schizophrenia, the one clinical-stage nicotinic alpha 7 modulator still left standing. Forum has not yet made a public announcement, we await any detail that may come from them on this. But in the meantime, this would be devastating news. It would leave the 5HT-6 antagonist programs from Lundbeck/Otsuka and Axovant as the most advanced procognitive candidates for Alzheimer’s. Unless and until a disease-modifier establishes efficacy in the Alzheimer’s realm, and nothing has yet produced a clearcut, consistent signal, symptomatic therapies will continue to receive clinical and investor emphasis, even if their magnitude of clinical effect is marginal–so long as they exert that effect safely. It appears that FRM-6124 has failed that critical test.
Addendum: Forum’s press release was finally sent out, and it provided some additional detail regarding the Phase III programs: The Alzheimer’s programs have been fully suspended, no additional study drug will be administered during the clinical hold.
The schizophrenia efficacy trials, which are fully enrolled, will continue, with additional GI safety monitoring provided. The premise is that elderly Alzheimer’s patients, who have a documented elevated incidence of GI disorders, may be particularly–or even uniquely– vulnerable to this AE. No patients in the schizophrenia trials have shown this AE (they have an average age of 40) hence the decision to allow the completion of the two efficacy trials. However, a longterm safety study in CIAS was halted, so the FDA is hedging their bets regarding FRM-6124’s safety in even the younger CIAS population.