Axsome Therapeutics has dosed the first patient in the Phase 3 FORWARD trial of AXS-14 (esreboxetine) for fibromyalgia, evaluating durable symptom control in a randomized withdrawal study design.
Written By: Pharmacally Medical News Desk
Axsome Therapeutics has announced that the first participant has been dosed in the Phase 3 FORWARD trial evaluating AXS-14 (esreboxetine) for the treatment of fibromyalgia. The milestone marks an important step in developing a potential new therapy for a condition that affects millions yet remains difficult to manage with current options.
The FORWARD study will assess whether AXS-14 can maintain symptom control in patients who initially respond to the therapy. Axsome aims to address the significant unmet need for treatments that provide durable relief without intolerable side effects.
Trial Design and Primary Endpoint
FORWARD, which stands for Fibromyalgia Response with Esreboxetine Evaluated Using a Randomized Withdrawal Research Design, is a multicenter, double-blind, placebo-controlled Phase 3 trial. The study includes an initial 12-week open-label treatment phase in which all enrolled patients receive AXS-14.
Participants who achieve a meaningful clinical response during this period will enter a randomized phase and be assigned in a 1:1 ratio to either continue AXS-14 at 8 mg once daily or switch to a matching placebo. This double-blind phase will last up to 12 weeks or until a loss of therapeutic response occurs.
The primary endpoint is the time from randomization to loss of response, a design intended to determine whether continued treatment with AXS-14 can sustain benefits compared with placebo withdrawal.
About Fibromyalgia
Fibromyalgia is a chronic neurological pain disorder characterized by widespread musculoskeletal pain, persistent fatigue, sleep disturbance, and cognitive difficulties often described as brain fog. Many patients also experience depression, sensory hypersensitivity, headaches, and tingling sensations in the extremities.
The condition affects an estimated 17 million people in the United States and carries a heavy personal and economic burden. Daily functioning, employment, and social participation are frequently impaired. Although several medications are approved for fibromyalgia, real-world outcomes remain suboptimal. More than half of patients discontinue therapy within the first year, commonly due to inadequate relief or poor tolerability.
About AXS-14
AXS-14 contains esreboxetine, a highly selective and potent norepinephrine reuptake inhibitor. Esreboxetine is the active SS-enantiomer of racemic reboxetine and is designed to enhance noradrenergic signalling involved in central pain modulation.
By targeting mechanisms believed to underlie centralized pain processing, AXS-14 may offer a different therapeutic approach compared with currently available agents.
Axsome’s CNS Portfolio
Axsome Therapeutics focuses on developing novel treatments for central nervous system disorders. The company already markets FDA-approved therapies for major depressive disorder, excessive daytime sleepiness related to narcolepsy and obstructive sleep apnea, and migraine.
Its pipeline includes multiple late-stage programs aimed at neurological and psychiatric conditions that collectively affect more than 150 million people in the United States. The FORWARD trial represents a key component of this strategy to deliver therapies that meaningfully improve patient outcomes.
Looking Ahead
Enrolment in the FORWARD trial is ongoing across multiple clinical sites. If successful, the study could support regulatory submissions and potentially expand treatment choices for people living with fibromyalgia, a disorder where new options are urgently needed.
Reference
Axsome Therapeutics Initiates FORWARD Phase 3 Trial of AXS-14 for the Management of Fibromyalgia, 15 January 2026, Axsome Therapeutics Initiates FORWARD Phase 3 Trial of AXS-14 for the Management of Fibromyalgia | Axsome Therapeutics, Inc.