Axsome Therapeutics has hit a costly snag in its mission to bring esreboxetine to market for fibromyalgia. The FDA has refused to review the CNS specialist’s new drug application (NDA) for the asset, with the agency determining that one of the two trials in the filing was not up to snuff.
One of the placebo-controlled trials used a 12-week endpoint and fixed dosing, and was deemed adequate and well-controlled by the FDA. The phase 2 study that prompted the agency’s refuse to file (RTF) letter instead used an 8-week endpoint and flexible dosing. Axsome said in a June 9 release that the agency didn't ask any questions about the results of the trials, both of which hit their primary endpoints.
Both trials were conducted by Pfizer. The Big Pharma licensed esreboxetine to Axsome for fibromyalgia in 2020 as part of a broader deal that included all the data related to depression cast-off reboxetine; esreboxetine is a variant of reboxetine (Edronax) designed to be more potent and selective than the drug approved to treat depression in certain parts of the world.
“The clear feedback provided by the FDA’s Division of Anesthesiology, Addiction Medicine and Pain Medicine allows us to move expeditiously with the continued development of this important investigational medicine for the approximately 17 million patients in the U.S. living with fibromyalgia,” Axsome CEO Herriot Tabuteau, M.D., said in the release. “We are well positioned to initiate a new controlled trial that will incorporate the FDA’s feedback by the end of 2025.”
This new trial will be a phase 3 study and will mimic the trial that the FDA found sufficient, with a 12-week endpoint and fixed dosing, an Axsome spokesperson told Fierce Biotech.
Axsome had about $301 million in cash and cash equivalents on March 31, according to the New York biotech’s first quarter earnings report.
“Given the agency’s request, we are inclined to believe that the RTF is only related to trial design and was not related to any questions about study data,” analysts from William Blair wrote in a June 9 note.
“We expect shares to be down modestly in response to the fibromyalgia RTF letter,” the analysts added, “but ultimately this news has limited impact on our growth thesis for Axsome.”
Axsome’s stock slipped in the morning as the RTF letter became public knowledge, but bounced back to $112 per share by 11 a.m. ET.
The neuro-focused company has also been working to revitalize reboxetine, called AXS-12 at Axsome, as a treatment for narcolepsy. In a May earnings release, Axsome said that it plans on filing an NDA for AXS-12 in the second half of 2025.
Pfizer originally developed reboxetine to treat depression, with the asset securing a provisional approval from the FDA in 1999 that was yanked back a couple of years later. A 2010 analysis of the compound deemed it “ineffective and potentially harmful.” The troubled drug was approved for depression in Europe in 1997, where it is primarily sold under the name Edronax.
Editor's note: This story was updated at 2:30pm E.T. to add further information about the new clinical trial Axsome is planning.