FDA concluded that AXS-14’s New Drug Application was not sufficiently complete for substantive review, citing concerns with one of two clinical trials in fibromyalgia patients.
The FDA has issued a Refusal to File (RTF) letter to Axsome Therapeutics regarding the company’s New Drug Application (NDA) for AXS-14 (esreboxetine), intended for the management of fibromyalgia. According to the company, the FDA concluded that the NDA was not sufficiently complete for a substantive review, citing concerns with one of the two placebo-controlled trials submitted. The study in question was deemed inadequate due to its eight-week primary endpoint and flexible-dose design.1
“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 US living with fibromyalgia,” said Herriot Tabuteau, MD, CEO, Axsome Therapeutics, in a press release. “We are well positioned to initiate a new controlled trial that will incorporate the FDA’s feedback by the end of 2025.”
Despite the issues raised about the second of the two trials, the FDA acknowledged the adequacy of the first trial, which used a 12-week endpoint and a fixed-dose approach. However, the agency did not question the positive results of either study, both of which met their primary endpoints. In response, Axsome plans to initiate a new controlled study, aligned with the FDA’s requirements, in Q4 of this year.1
According to the Centers for Disease Control and Prevention, fibromyalgia affects approximately four million adults in the United States, accounting for about 2% of the population. While it can impact individuals of all ages, it is most commonly diagnosed in middle-aged adults, with likelihood increasing with age. Additionally, people with lupus or rheumatoid arthritis are more likely to develop fibromyalgia. Other risk factors include:
Globally, approximately 160 million people are currently living with fibromyalgia. It often takes around five years for patients to receive an accurate diagnosis. According to MoreGoodDays, the average cost of fibromyalgia in the United States ranges from $16 billion to $20 billion annually, encompassing medications, physician visits, hospital stays, lost productivity, and disability payments.2 Additionally, individuals living with fibromyalgia face approximately double the average medical costs compared to the general US population.
Ninety percent of people with fibromyalgia also experience sleep issues. Furthermore, 80% report fatigue, 50% suffer from cognitive and memory problems, and 20% live with anxiety and depression. Notably, 40% to 60% of individuals with fibromyalgia are unemployed due to the severity of the condition.3
“As highlighted in the FDA’s Patient-Focused Drug Development Initiative report The Voice of the Patient: Fibromyalgia, patients with fibromyalgia experience debilitating widespread pain, fatigue, and functional impairment, and report living with constant stigmatization, anxiety, depression, and fear of ongoing or worsening symptoms,” continued Tabuteau, in the press release. “We are excited and motivated by the potential for AXS-14 to address this high unmet medical need for patients, as evidenced by the consistent efficacy demonstrated to date across a broad range of fibromyalgia symptoms, including significant improvements in pain, function, and fatigue, in the completed trials.”
References
1. Axsome Therapeutics Provides Update on the New Drug Application (NDA) for AXS-14 for the Management of Fibromyalgia. Axsome. June 9, 2025. Accessed June 9, 2025. https://axsometherapeuticsinc.gcs-web.com/news-releases/news-release-details/axsome-therapeutics-provides-update-new-drug-application-nda-axs
2. Fibromyalgia. CDC. Accessed June 9, 2025. https://archive.cdc.gov/www_cdc_gov/arthritis/types/fibromyalgia.htm
3. Fibromyalgia by Numbers: Key Statistics You Need to Know. MoreGoodDays. Accessed June 9, 2025. https://www.moregooddays.com/post/fibromyalgia-by-numbers-key-statistics-you-need-to-know
