The FDA has sent a Refuse-to-File letter to Axsome Therapeutics in response to its new drug application for AXS-14, or esreboxetine, for the management of fibromyalgia.
The agency’s preliminary review of the application found that it was not sufficiently complete to permit a substantive review. Specifically, the FDA did not consider the second of the two placebo-controlled trials in the submission to be adequate and well controlled because its primary end point was at eight weeks and
JUNE 10, 2025
FDA Issues Refuse-to-File Letter for Experimental Fibromyalgia Drug
The FDA has sent a Refuse-to-File letter to Axsome Therapeutics in response to its new drug application for AXS-14, or esreboxetine, for the management of fibromyalgia.
The agency’s preliminary review of the application found that it was not sufficiently complete to permit a substantive review. Specifically, the FDA did not consider the second of the two placebo-controlled trials in the submission to be adequate and well controlled because its primary end point was at eight weeks and it used a flexible-dose paradigm, according to the company, in a press release.
The FDA indicated that the first of the two placebo-controlled trials in the submission, which used a 12-week end point and a fixed-dose paradigm, was adequate and well controlled. The agency did not raise any questions relating to the positive results of the studies, both of which met their primary end points, according to Axsome’s press release.
To address the FDA’s response, Axsome announced that it will conduct an additional controlled trial, which will use a fixed-dose paradigm and a 12-week primary end point, as requested by the FDA. The company anticipates initiating this trial in the fourth quarter of 2025.
“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,” said Herriot Tabuteau, MD, the CEO of Axsome. “We are well positioned to initiate a new controlled trial that will incorporate the FDA’s feedback by the end of 2025.
“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,” Tabuteau added.
AXS-14 is a highly selective and potent norepinephrine reuptake inhibitor for the management of fibromyalgia and other conditions. Esreboxetine, the SS enantiomer of reboxetine, is more potent and selective than racemic reboxetine. AXS-14 is an investigational drug product not approved by the FDA.
Based on a press release from Axsome.
The agency’s preliminary review of the application found that it was not sufficiently complete to permit a substantive review. Specifically, the FDA did not consider the second of the two placebo-controlled trials in the submission to be adequate and well controlled because its primary end point was at eight weeks and it used a flexible-dose paradigm, according to the company, in a press release.
The FDA indicated that the first of the two placebo-controlled trials in the submission, which used a 12-week end point and a fixed-dose paradigm, was adequate and well controlled. The agency did not raise any questions relating to the positive results of the studies, both of which met their primary end points, according to Axsome’s press release.
“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,” said Herriot Tabuteau, MD, the CEO of Axsome. “We are well positioned to initiate a new controlled trial that will incorporate the FDA’s feedback by the end of 2025.
“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,” Tabuteau added.
AXS-14 is a highly selective and potent norepinephrine reuptake inhibitor for the management of fibromyalgia and other conditions. Esreboxetine, the SS enantiomer of reboxetine, is more potent and selective than racemic reboxetine. AXS-14 is an investigational drug product not approved by the FDA.
Based on a press release from Axsome.