FORUM Pharma Halts Clinical Trials for Alzheimer’s and Schizophrenia Drug
September 15, 2015
By Mark Terry, BioSpace.com Breaking News Staff
The U.S. Food and Drug Administration (FDA) advised Waltham, Mass.-based FORUM Pharmaceuticals to halt its clinical trials of encenicline for Alzheimer’s disease yesterday.
The FDA cited a small number of serious gastrointestinal (GI) side effects in the studies. As a result, FORUM halted the trial, discontinuing the medication and no new patients will be recruited until the clinical hold is lifted. The company is working with the FDA on a plan to continue the study.
In addition, the FDA told the company that a trial in cognitive impairment in schizophrenia (CIS) has also been placed on a clinical hold. Two fully enrolled Phase III efficacy trials, however, that are evaluating encenicline to treat CIS will continue.
In June 2015, FORUM received Fast Track designation for encenicline to treat CIS from the FDA.
Encenicline is an oral, highly brain-penetrant, selective agonist of the alpha 7 receptor that is found in hippocampal and cortical neurons involved in cognition, in other words, brain cells involved in thinking. FORUM believes the drug activates alpha 7 receptors to increase its response to a naturally occurring neurotransmitter called acetylcholine. This, in turn, is believed to activate brain networks related to sensory gating, attention and cognition.
A number of companies are working on Alzheimer’s medications, although it’s a difficult area with far more failures than successes. Swiss-based Roche reported in Dec. 2014 that it was discontinuing Scarlet RoAD, a Phase III study of gantenerumab on pre-dementia Alzheimer’s disease. In March 2015 Biogen, Inc. showed positive results of its Alzheimer’s drug, aducanumab.
Another Roche drug, in an agreement with Germany-based Evotec, announced in July that its Phase IIb clinical trial of sembragiline in Alzheimer’s failed to meet its primary endoint.
Eli Lilly and Company presented positive results for its Alzheimer’s drug, solanezumab, which had previously shown disappointing clinical trials in 2012. The company has shifted its focus to a subgroup of AD patients with a mild form of the disease that responded to the drug.
A 2014 report in Alzheimer’s Research UK indicated that 244 Alzheimer’s drugs were tested between 2002 and 2012, and only one was approved, Lundbeck A/S ’s Ebixa. Even the few that are approved and on the market aren’t considered to be terribly effective. The biggest AD drug on the market is Eisai Company, Ltd.’s Aracept. Others are Exelon, by Novartis , Razadyne by Janssen, and Namenda, by Actavis . Jeffrey Holford, an analyst with Jefferies and Co., predicted that if the Lilly drug was approved, it could hit annual sales of more than $3 billion globally.
In June 2015 Axovant Sciences Ltd. , which focuses on Alzheimer’s drugs, went public, raising $315 million overnight, the largest deal ever for a pre-revenue biotech company. The company’s product, RVT-101, which it bought from GlaxoSmithKline for $5 million and milestone payments, has shown some success in alleviating AD symptoms, but did not prevent the disease from progressing.
Mark Schoenebaum, a biotech analyst who leads the biotech team at ISI Evercore, wrote an investor note in May that tries to pin down the size of the AD drug market. “There are 600,000 mild AD patients in the U.S.,” he wrote. “At a net price of around $20,000 (below TNFs), 65 percent penetration would yield a potential sales opportunity of around $8 billion in the U.S. alone. The ex-U.S. patient opportunity is similar, but price would probably be lower.”