FDA Refuses to Review Axsome's Fibromyalgia Drug, Company Plans New Trial

Axsome Therapeutics has encountered a significant setback in its efforts to bring esreboxetine, a potential treatment for fibromyalgia, to market. The U.S. Food and Drug Administration (FDA) has refused to review the company's new drug application (NDA) for the asset, citing concerns over one of the two trials included in the filing.

FDA's Concerns and Axsome's Response

The FDA's refuse to file (RTF) letter focused on the design of one of the placebo-controlled trials submitted by Axsome. While one trial, which used a 12-week endpoint and fixed dosing, was deemed adequate and well-controlled, the agency found issues with a phase 2 study that employed an 8-week endpoint and flexible dosing.

Axsome CEO Herriot Tabuteau, M.D., stated, "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."

In response to the FDA's decision, Axsome has announced plans to initiate a new phase 3 trial by the end of 2025. This study will mirror the design of the trial that met FDA approval, incorporating a 12-week endpoint and fixed dosing.

Esreboxetine's Background and Market Implications

Esreboxetine, originally developed by Pfizer, was licensed to Axsome in 2020 as part of a broader deal that included data related to reboxetine, a depression treatment. Esreboxetine is a variant of reboxetine designed to be more potent and selective.

Despite the setback, analysts from William Blair believe the RTF letter is related solely to trial design and not to concerns about study data. They expect only a modest impact on Axsome's stock price, noting that this news has limited influence on their overall growth thesis for the company.

Axsome's stock initially dipped following the announcement but recovered to $112 per share by 11 a.m. ET on the day of the news release. The company reported approximately $301 million in cash and cash equivalents as of March 31, 2025, according to its first-quarter earnings report.