Restructuring Looms for Forum as Neuro Drug Fails Key Clinical Test

Xconomy Boston — 

Forum Pharmaceuticals has been pursuing a more than decade-long quest to develop a drug that might help people with a variety of neurological disorders to think more clearly. Unfortunately, however, it’s come up short in its biggest test to date—two large Phase 3 clinical trials in patients with schizophrenia.

Waltham, MA-based Forum revealed the topline results from two late-stage studies of encenicline, a drug it’s been developing as a cognitive enhancer for a variety of neurological diseases, among them Alzheimer’s disease and schizophrenia. Forum said today that both studies failed their main goals—the drug didn’t have a statistically significant benefit on cognitive function.

The news leaves Forum, which has been backed with hundreds of millions of dollars by financial behemoth Fidelity, in a precarious position. Its big war chest has dwindled, and the future of its most advanced drug prospect is in doubt.

Late last year, the FDA placed a clinical hold on two late-stage studies of encenicline in Alzheimer’s due to gastrointestinal safety problems. Now the drug has failed in schizophrenia. Though Forum said “activity was observed across certain sub-groups and secondary endpoints,” that wasn’t enough encouragement to plan further trials in schizophrenia. What’s more, Forum said it saw “an unexpectedly high placebo response”—something known to plague clinical trials in neurological diseases.

Forum said that due to the results, it’s implementing a “significant restructuring” to “appropriately scale its spending and resources and evaluate a potential path forward, if any.” It didn’t specify whether it was referring to encenicline, or the company itself, but encenicline is by far the company’s closest drug to market. The Boston Business Journal reported earlier today that the company has already notified the state of Massachusetts that it’ll ax as many as 89 employees, though that was before Forum revealed the two studies had failed (a spokesperson said Friday that the company has a total of 130 employees).

Forum declined to comment beyond the announcement.

Forum’s CEO is well-known Boston biotech veteran Deborah Dunsire, the former CEO of Millennium Pharmaceuticals. Dunsire left Millennium (owned by Takeda) in May 2013 and surfaced two months later as the CEO of Forum, then known as EnVivo Pharmaceuticals. It was a surprising move, in part because Dunsire has spent much of her career in oncology—at Millennium, for instance, she oversaw the company’s meteoric rise in the cancer treatment field after the approval of the myeloma drug bortezomib (Velcade). “It is uncomfortable, because in oncology, I know who to call about anything. I know the field really, really well,” Dunsire told Xconomy at the time. “Here, I’m learning. But that’s actually very exciting.”

She took on an unusual company, as far as biotechs go. Forum started more than a decade ago, and has mainly been bankrolled by Fidelity, thanks to former Fidelity CEO Ned Johnson’s passion and support for Alzheimer’s research. That type of backing gave Forum the freedom not to have to do deals or court outside investors to survive. Fidelity wanted the company to stay private and commercialize its own drugs, despite the high cost. Forum, for instance, ran two big, expensive trials of encenicline in schizophrenia, consisting of over 1,500 patients at more than 200 clinical sites, on its own bankroll—a highly unusual thing for a startup biotech to do without the help of a partner such as a big pharmaceutical company.

Dunsire’s plan, as I wrote last year, however, was to find outside investors to lay the foundation for a future IPO. But the key to making that happen was the success of encenicline. With the drug’s future now in doubt, it’s unclear what the company’s next steps are.

Check out this story for more on the history of Forum and encenicline.