September 12, 2017
By Alex Keown, BioSpace.com Breaking News Staff
CAMBRIDGE, Mass. – Shares of Sage Therapeutics are down more than 18 percent this morning after the company announced its epilepsy drug Brexanolone failed to help patients with a severe form of the disease.
Phase III trial data showed that Brexanolone (Sage-547) failed miserably to differentiate itself from placebo. Sage’s drug generated a 43.9 percent response compared to a 42.4 percent response from placebo. The drug had a p-value of .8775, Sage said. Additionally the company said secondary endpoint results were consistent with primary endpoints, meaning it did not outdo placebo.
Brexanolone, an allosteric modulator of both synaptic and extrasynaptic GABAA receptors, was being developed to treat super-refractory status epilepticus (SRSE), which is a severe form of the disease that causes seizures that last longer than five minutes. Patients with SRSE can experience seizures caused by a number of different things. SRSE patients do not respond to first-, second- or third-line treatments and are placed in a medically induced coma. Sage’s drug was being developed to wean patients off that third-line treatment to determine if the seizure condition has been resolved. It is estimated that there are between 25,000 and 41,000 cases of SRSE annually in the United States. There are no treatments for SRSE currently approved by the U.S. Food and Drug Administration.
Sage Chief Executive Officer Jeff Jonas expressed disappointment in the trial outcome. Although a failure, Jonas said the Sage R&D team made “significant progress” in learning how to treat SRSE patients.
“SRSE is a complicated condition that is poorly understood, and I want to thank the patients, their families, and the investigators who participated in the STATUS Trial. Although we did not meet the primary endpoint, this first-ever trial in a highly variable and complex patient population confirms that research in a critical care unit is possible and deepens our understanding of GABA mechanisms and their effect on brain circuitry,” Jonas said in a statement. “As we continue examining data from the STATUS Trial in the coming weeks, I’m hopeful this information will inform current treatments, and aid in the development of future treatments for patients with SRSE.”
Brexanolone is also being developed for treatment of postpartum depression. Earlier this year, the FDA granted it Breakthrough Therapy Designation for that indication. It received a similar status from the European Medicines Agency. Brexanolone is in Phase III for postpartum depression.
Because the drug failed to distinguish itself against placebo in the 132 patient trial, there are some who question whether or not Brexanolone will be successful in treating postpartum depression. Leerink analyst Paul Matteis seemed to dismiss those concerns. In a note published by Endpoints News, Matteis said it would be difficult to see the PPD results being tainted by the SRSE issue. He said the Phase III PPD trial has placebo-controlled data and a better understood history than SRSE. Additionally, he noted the FDA’s awarding of Breakthrough Therapy Designation.
