Feds clamp a hold on Forum's PhIII Alzheimer's study following GI events

The FDA has slammed the brakes on the late-stage Alzheimer's development program for encenicline after investigators reported a "small" number of serious gastrointestinal adverse events among patients taking the drug, the lead therapy for Waltham, MA-based Forum Pharmaceuticals.

Deborah Dunsire

Funded by Fidelity Biosciences and run by former Millennium CEO Deborah Dunsire, a high-profile executive in the Boston area, Forum changed its name from EnVivo as it accelerated its alpha 7 receptor drug into Phase III. In the last few months the drug won fast-track status at the FDA and completed enrollment in Phase III for schizophrenia. The late-stage Alzheimer's study was launched in early 2014.

"Forum has discontinued all study medication in the AD (Alzheimer's) trials and no new patients will be recruited into the studies until the clinical hold is lifted," the company said in a statement. "Forum plans to work with the FDA to determine a path forward to lift the clinical hold in the AD trial program."

There was no explanation of the kind of GI events that might be linked to the drug.

A long-term extension study of encenicline in schizophrenia was put on hold as well, though two Phase III trials will continue to treat cognitive impairment in schizophrenia, with investigators keeping an eye out on similar adverse events.

The drug works by sensitizing a key nicotinic acetylcholine receptor, which Forum had hoped could be done without the toxic effects seen in alternative approaches which have scuttled a series of Alzheimer's programs in recent years. By sensitizing the receptor, the company had hoped that it would improve its response to a neurotransmitter, thereby amping up cognitive abilities.

The recent Phase II data reported for schizophrenia noted that the 0.27-mg dose of the drug scored a statistically significant improvement in cognition scores, though the 0.9-mg dose failed that measure.

Over the past decade the failure rate on Alzheimer's drugs has run at 99%, highlighting the lack of scientific consensus on what causes the memory-wasting disease and how it can be treated. Nevertheless, with millions of patients suffering from the disease, companies like Eli Lilly ($LLY) continue to hammer away in the clinic, knowing that just about anything that can be approved would likely generate a megablockbuster market, regardless of how effective it may be.

It's extraordinarily unusual to see a private, venture-backed biotech undertaking a hugely expensive, and risky, Phase III program like this. While the potential rewards may be enormous, the cost would make most VCs shudder, which is why Big Pharma companies like Lilly and Merck ($MRK) have led the way in late-stage testing.

- here's the release

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