Axsome Therapeutics Initiates FORWARD Phase 3 Trial of AXS-14 for the Management of Fibromyalgia

Rhea-AI Summary

Axsome Therapeutics (NASDAQ: AXSM) announced dosing of the first patient in the FORWARD Phase 3 trial of AXS-14 (esreboxetine) for the management of fibromyalgia on January 15, 2026. FORWARD is a multicenter, double-blind, placebo-controlled, randomized withdrawal trial that starts with a 12-week open-label AXS-14 treatment period followed by randomization 1:1 to continue AXS-14 8 mg once daily or switch to matching placebo for up to 12 weeks or until loss of therapeutic response. The primary endpoint is time from randomization to loss of therapeutic response. The design targets patients who achieve a treatment response during the open-label period and evaluates durability of effect versus placebo withdrawal.

Positive

• Phase 3 FORWARD trial initiated with first patient dosed on Jan 15, 2026
• Randomized withdrawal design evaluates durability of AXS-14 response
• Dosing regimen defined as AXS-14 8 mg once daily
• Clear primary endpoint: time to loss of therapeutic response
• Structured enrollment: 12-week open-label then up to 12-week randomized period

Negative

• No efficacy or safety readouts yet from FORWARD to inform commercialization
• Study requires patients to achieve response in open-label period before randomization
• Outcome timeline depends on completing both 12-week periods, delaying near-term impact

News Market Reaction – AXSM

-1.62%

1 alert

-1.62% News Effect

On the day this news was published, AXSM declined 1.62%, reflecting a mild negative market reaction.

Data tracked by StockTitan Argus on the day of publication.

Key Figures

Open-label duration: 12 weeks Randomized period: Up to 12 weeks Randomization ratio: 1:1 +1 more

4 metrics

Open-label duration 12 weeks AXS-14 open-label treatment period before randomization

Randomized period Up to 12 weeks Double-blind treatment period until loss of response

Randomization ratio 1:1 AXS-14 continued vs placebo after response

AXS-14 dose 8 mg once daily Dose used in FORWARD Phase 3 randomized period

Market Reality Check

Price: $163.89 Vol: Volume 381,791 is below t...

low vol

$163.89 Last Close

Volume Volume 381,791 is below the 791,363 20-day average, suggesting a relatively muted pre-news trading day. low

Technical Shares at $177.01 trade above the $121.92 200-day MA and about 4% below the $184.40 52-week high.

Peers on Argus

Biotech peers like NUVL (+5.84%) and RYTM (+5.43%) were positive, but momentum d...

1 Up

Biotech peers like NUVL (+5.84%) and RYTM (+5.43%) were positive, but momentum data show only ABVX in scanners and no confirmed sector-wide move tied to this headline.

Historical Context

5 past events · Latest: Jan 12 (Positive)

Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Jan 12	Preliminary revenues	Positive	+4.4%	Preliminary Q4 and full-year 2025 net product revenue with strong growth.
Dec 31	Regulatory update	Positive	+22.8%	FDA acceptance and Priority Review of sNDA for AXS-05 in Alzheimer’s agitation.
Dec 31	Regulatory update	Positive	+22.8%	FDA pre-NDA meeting minutes support AXS-12 NDA submission in narcolepsy.
Nov 20	Investor conferences	Neutral	-2.4%	Announcement of participation in upcoming December 2025 investor conferences.
Nov 06	Pipeline acquisition	Positive	+2.7%	Acquisition of AZD7325 GABA-A modulator rights for epilepsy development.

Pattern Detected

AXSM has often seen positive price reactions to value-adding clinical and regulatory updates, with occasional dips on neutral conference-related news.

Recent Company History

Over the last few months, Axsome reported strong growth, with Q4 2025 preliminary net product revenue of $196.0M and full-year $638.5M, which coincided with a 4.39% gain. On Dec 31, 2025, FDA Priority Review for AXS-05 and supportive pre-NDA feedback for AXS-12 each aligned with a 22.75% rise. An epilepsy asset acquisition on Nov 6, 2025 also saw shares up 2.74%, while a neutral conference participation update on Nov 20, 2025 was followed by a modest decline.

Market Pulse Summary

This announcement details initiation of the FORWARD Phase 3 trial of AXS-14 in fibromyalgia, using a...

Analysis

This announcement details initiation of the FORWARD Phase 3 trial of AXS-14 in fibromyalgia, using a randomized-withdrawal, double-blind, placebo-controlled design with 12-week open-label and blinded periods. In context of Axsome’s recent late-stage CNS progress and regulatory milestones, it adds another potential indication to the pipeline. Investors may track enrollment progress, durability of therapeutic response as the primary endpoint, and how this program complements existing commercial products and other Phase 3 assets.

Key Terms

phase 3, double-blind, placebo-controlled, multicenter, +4 more

8 terms

phase 3 medical

"FORWARD Phase 3 trial of AXS-14 (esreboxetine) for the management"

Phase 3 is the late-stage clinical testing step for a new drug or medical treatment, where the product is given to large groups of patients to confirm effectiveness, monitor side effects, and compare it to standard care. Successful Phase 3 results are often the final scientific hurdle before regulators decide on approval and market launch—like passing a final exam before graduation—and can sharply change a company's valuation and future revenue prospects.

double-blind medical

"is a Phase 3, double-blind, placebo-controlled, multicenter, randomized"

A double-blind process means that neither the people conducting an activity nor the people involved know certain key details, such as who is receiving a treatment or a placebo. This approach helps prevent bias from influencing the results, making the outcome more trustworthy. For investors, it ensures that decisions or judgments are based on unbiased information rather than preconceived opinions or expectations.

placebo-controlled medical

"Phase 3, double-blind, placebo-controlled, multicenter, randomized withdrawal"

"Placebo-controlled" describes a testing method where one group receives the actual treatment or intervention, while another group receives a harmless, inactive version called a placebo. This approach helps determine whether the real treatment has genuine effects beyond psychological expectations. For investors, understanding this ensures confidence that reported benefits are real and not influenced by bias or false perceptions.

multicenter medical

"double-blind, placebo-controlled, multicenter, randomized withdrawal trial"

A multicenter study or trial is conducted at several independent locations or clinics rather than a single site, so researchers collect data from diverse groups and settings. For investors, multicenter designs matter because they increase the credibility and generalizability of results, reduce the risk that findings are due to one local population or practice, and often speed enrollment — all factors that can affect regulatory outcomes, market confidence and commercial prospects.

randomized withdrawal medical

"Esreboxetine Evaluated Using a Randomized Withdrawal Research Design"

A randomized withdrawal is a clinical trial design where people who initially get better on a treatment are later randomly assigned either to keep taking it or to stop, so researchers can measure whether benefits last and whether problems reappear. Think of testing a new routine by removing it for half the group to see if results continue. Investors care because these results reveal how durable a drug’s effects and safety profile are, which affect approval, labeling, prescribing and long-term sales.

open-label medical

"consisting of an open-label AXS-14 treatment period and a randomized"

Open-label describes a situation where everyone involved in a study or process knows the full details, such as who is receiving a treatment or intervention. For investors, understanding whether a project or product is open-label helps gauge the level of transparency and potential biases, influencing trust and decision-making. It’s like knowing whether a test or experiment is conducted openly or behind closed doors.

fibromyalgia medical

"trial of AXS-14 (esreboxetine) for the management of fibromyalgia."

Fibromyalgia is a long-term condition that causes widespread body pain, extreme tiredness, and problems with sleep, memory and mood; people often feel unusually sensitive to normal touch or pressure, and symptoms can fluctuate from day to day. It matters to investors because it affects workforce productivity, healthcare spending, and demand for treatments—so advances in diagnostics, drugs, or care delivery can change market size and company prospects, much like a fuel problem that reduces a car’s performance and reliability.

endpoint medical

"The primary endpoint will be the time from randomization"

An endpoint in clinical research is the specific outcome investigators decide in advance to measure whether a treatment is effective or safe, such as symptom improvement, survival time, or a change in a lab value. For investors it matters because meeting or missing these pre-set goals is the main signal regulators and the market use to judge a drug’s prospects—like a race’s finish line that determines if a product can move forward, win approval, and generate revenue.

AI-generated analysis. Not financial advice.

NEW YORK, Jan. 15, 2026 (GLOBE NEWSWIRE) -- Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company leading a new era in the treatment of central nervous system (CNS) disorders, today announced the first patient has been dosed in the FORWARD Phase 3 trial of AXS-14 (esreboxetine) for the management of fibromyalgia.

FORWARD (Fibromyalgia Response with Esreboxetine Evaluated Using a Randomized Withdrawal Research Design) is a Phase 3, double-blind, placebo-controlled, multicenter, randomized withdrawal trial in patients with fibromyalgia consisting of an open-label AXS-14 treatment period and a randomized, double-blind treatment period. Patients achieving a treatment response during the 12-week open-label period will be randomized in a 1:1 ratio to continue AXS-14 (8 mg) once daily or to switch to matching placebo for up to 12 weeks or until a loss of therapeutic response occurs. The primary endpoint will be the time from randomization to loss of therapeutic response.

About Fibromyalgia

Fibromyalgia is a chronic, debilitating neurological pain disorder that affects approximately 17 million people in the U.S.^1,2 Fibromyalgia is considered to be mediated mainly in the central nervous system.² It is characterized by widespread pain, fatigue, disturbed sleep, depression, cognitive impairment, and hypersensitivity to sensory stimuli.^1,2 Other symptoms of this disorder can include tingling in the hands and feet and headaches.^2-4 Fibromyalgia has considerable detrimental effects on physical, emotional, social, and day-to-day functioning and is associated with significant economic burden and reduced quality of life.⁵ Despite its prevalence and impact, current treatment options remain limited. Many patients experience inadequate symptom control or intolerable side effects, with over 50% of fibromyalgia patients discontinuing their treatment within the first year.⁶

About AXS-14

AXS-14 (esreboxetine) is a highly selective and potent norepinephrine reuptake inhibitor being developed for the management of fibromyalgia. Esreboxetine is the SS-enantiomer of racemic reboxetine. AXS-14 is an investigational drug product not approved by the FDA.

About Axsome Therapeutics

Axsome Therapeutics is a biopharmaceutical company leading a new era in the treatment of central nervous system (CNS) conditions. We deliver scientific breakthroughs by identifying critical gaps in care and develop differentiated products with a focus on novel mechanisms of action that enable meaningful advancements in patient outcomes. Our industry-leading neuroscience portfolio includes FDA-approved treatments for major depressive disorder, excessive daytime sleepiness associated with narcolepsy and obstructive sleep apnea, and migraine, and multiple late-stage development programs addressing a broad range of serious neurological and psychiatric conditions that impact over 150 million people in the United States. Together, we are on a mission to solve some of the brain’s biggest problems so patients and their loved ones can flourish. For more information, please visit us at www.axsome.com and follow us on LinkedIn and X.

Forward Looking Statements

Certain matters discussed in this press release are “forward-looking statements”. The Company may, in some cases, use terms such as “predicts,” “believes,” “potential,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. In particular, the Company’s statements regarding trends and potential future results are examples of such forward-looking statements. The forward-looking statements include risks and uncertainties, including, but not limited to, the commercial success of the Company’s SUNOSI^®, AUVELITY^®, and SYMBRAVO^® products and the success of the Company’s efforts to obtain any additional indication(s) with respect to solriamfetol and/or AXS-05; the Company’s ability to maintain and expand payer coverage; the success, timing and cost of the Company’s ongoing clinical trials and anticipated clinical trials for the Company’s current product candidates, including statements regarding the timing of initiation, pace of enrollment and completion of the trials (including the Company’s ability to fully fund the Company’s disclosed clinical trials, which assumes no material changes to the Company’s currently projected revenues or expenses), futility analyses and receipt of interim results, which are not necessarily indicative of the final results of the Company’s ongoing clinical trials, and/or data readouts, and the number or type of studies or nature of results necessary to support the filing of a new drug application (“NDA”) for any of the Company’s current product candidates; the Company’s ability to fund additional clinical trials to continue the advancement of the Company’s product candidates; the timing of and the Company’s ability to obtain and maintain U.S. Food and Drug Administration (“FDA”) or other regulatory authority approval of, or other action with respect to, the Company’s product candidates, including statements regarding the timing of any NDA submission; the Company’s ability to successfully defend its intellectual property or obtain the necessary licenses at a cost acceptable to the Company, if at all; the Company’s ability to successfully resolve any intellectual property litigation, and even if such disputes are settled, whether the applicable federal agencies will approve of such settlements; the successful implementation of the Company’s research and development programs and collaborations; the success of the Company’s license agreements; the acceptance by the market of the Company’s products and product candidates, if approved; the Company’s anticipated capital requirements, including the amount of capital required for the commercialization of SUNOSI, AUVELITY, and SYMBRAVO and for the Company’s commercial launch of its other product candidates, if approved, and the potential impact on the Company’s anticipated cash runway; the Company’s ability to convert sales to recognized revenue and maintain a favorable gross to net sales; unforeseen circumstances or other disruptions to normal business operations arising from or related to domestic political climate, geo-political conflicts or a global pandemic and other factors, including general economic conditions and regulatory developments, not within the Company’s control. The factors discussed herein could cause actual results and developments to be materially different from those expressed in or implied by such statements. The forward-looking statements are made only as of the date of this press release and the Company undertakes no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstances.

Investors:
Ashley Dong
Director, Investor Relations
(929) 687-1614
adong@axsome.com

Media:
Darren Opland
Senior Director, Corporate Communications
(929) 837-1065
dopland@axsome.com

References:

1. Vincent A, et al. Prevalence of fibromyalgia: a population-based study in Olmsted County, Minnesota, utilizing the Rochester Epidemiology Project. Arthritis Care Res (Hoboken). 2013 May;65(5):786-92. https://pubmed.ncbi.nlm.nih.gov/23203795/
2. Clauw DJ. Fibromyalgia: a clinical review. JAMA. 2014 Apr 16;311(15):1547-55. https://pubmed.ncbi.nlm.nih.gov/24737367/
3. Clauw DJ. From fibrositis to fibromyalgia to nociplastic pain: how rheumatology helped get us here and where do we go from here? Ann Rheum Dis. 2024 Oct 21;83(11):1421-1427. https://pubmed.ncbi.nlm.nih.gov/39107083/
4. Bair MJ and Krebs EE. Fibromyalgia. Ann Intern Med. 2020;172:ITC33-ITC48. https://pubmed.ncbi.nlm.nih.gov/32120395/
5. Arnold LM, et al. Patient Perspectives on the Impact of Fibromyalgia. Patient Educ Couns. 2008 Oct;73(1):114-20. https://pubmed.ncbi.nlm.nih.gov/18640807/
6. Liu Y, et al. Treatment Patterns Associated with ACR-Recommended Medications in the Management of Fibromyalgia in the United States. J Manag Care Spec Pharm. 2016 Mar;22(3):263-71. https://pubmed.ncbi.nlm.nih.gov/27003556/

FAQ

What is the FORWARD Phase 3 trial design for AXS-14 (AXSM)?

FORWARD is a multicenter, double-blind, placebo-controlled randomized withdrawal trial with a 12-week open-label AXS-14 period, then 1:1 randomization to continue AXS-14 8 mg once daily or placebo for up to 12 weeks.

When was the first patient dosed in Axsome's FORWARD trial (AXSM)?

The first patient was dosed on January 15, 2026.

What is the primary endpoint of the FORWARD trial for AXS-14 (AXSM)?

The primary endpoint is the time from randomization to loss of therapeutic response.

What dose of AXS-14 is being tested in the FORWARD Phase 3 trial (AXSM)?

The trial uses AXS-14 8 mg once daily during the open-label and randomized phases.

How long are the treatment periods in the FORWARD trial (AXSM)?

There is a 12-week open-label treatment period followed by up to a 12-week randomized treatment period or until loss of therapeutic response.