March 25, 2016
By Mark Terry, BioSpace.com Breaking News Staff
Waltham, Mass.-based FORUM Pharmaceuticals, in light of two Phase III trial disappointments, is laying off half its staff and restructuring the company.
In September 2015, the U.S. Food and Drug Administration (FDA) advised FORUM to halt its clinical trials of encenicline for Alzheimer’s disease. A small number of serious gastrointestinal (GI) side effects had been observed.
Also, a second trial in cognitive impairment in schizophrenia (CIS) has been placed on a clinical hold. That trial hold was lifted in November. In June 2015, FORUM received Fast Track designation from the FDA to study encenicline to treat CIS.
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, or 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.
On March 21, the company notified the State of Massachusetts that it was laying off 77 employees over a 30-day period starting May 20. Another 12 staffers, the filing warned, could be laid off “if the company receives adverse clinical trial data.”
And then on March 24, FORUM announced topline results from two Phase III clinical trials in the CIS studies. Although encenicline showed a positive safety and tolerability profile, the drug failed to meet its co-primary endpoints in either study.
“These results were not what we might have hoped for on behalf of our patients,” said Deborah Dunsire, president and chief executive officer of FORUM, in a statement. “We wish to thank over 1,500 patients who participated as well as the investigators at more than 200 clinical sites.”
Although data is continuing to be analyzed, the trial showed unexpected high response rates from the placebo group in both trials.
As a result, the company announced it will undergo significant restructuring to, as the company stated, “appropriately scale its spending and resources and to evaluate a potential path forward, if any.”
Alzheimer’s and other neurobiological areas such as schizophrenia are notoriously difficult to study and develop drugs for. In Dec. 2014, Swiss-based Roche announced it was discontinuing Scarlet RoAD, a Phase III study of gantenerumab on pre-dementia Alzheimer’s disease. In July 2015, Roche, in an agreement with Germany-based Evotec, announced that its Phase IIb clinical study of sembragiline in Alzheimer’s failed to meet its primary endpoint.
In 2012, Eli Lilly and Company had disappointing results in its Alzheimer’s drug, solanezumab. It then shifted its focus to a subgroup of AD patients with a mild form of the disease that responded to the drug.
According to a 2014 report by the Alzheimer’s Research UK, between 2002 and 2012, 244 Alzheimer’s drugs were tested and only one was approved, Lundbeck A/S ’s Ebixa. Even those few drugs on the market aren’t considered to be very effective. The most successful AD drug on the market is Eisai Company, Ltd.’s Aracept. Others are Exelon, by Novartis , Razadyne by Janssen, and Nemenda, by Actavis .
In March 2015, Biogen, Inc. positive results for its Alzheimer’s drug, aducanumab. Even so, the drug appears to break up amyloid plaques, which are believed to be one of the causes of cognition problems in Alzheimer’s patients, but the data indicating the drug slowed disease progression wasn’t quite as convincing.
Dublin-based Prothena appears to be making some headway on drugs for AL amyloidosis and Parkinson’s disease, although they are still in very early trials. And New York-based Intra-Cellular Therapies is showing some positive results in two Phase III trials for bipolar depression and schizophrenia.
