Axsome Therapeutics Initiates CLARITY Phase 3 Trial of Solriamfetol in Adults with Major Depressive Disorder with Excessive Daytime Sleepiness Symptoms

Rhea-AI Summary

Axsome Therapeutics (NASDAQ: AXSM) announced dosing of the first patient in the CLARITY Phase 3 trial of solriamfetol for adults with major depressive disorder (MDD) with excessive daytime sleepiness (EDS) on Feb 24, 2026.

CLARITY is a double-blind, placebo-controlled, multicenter randomized withdrawal trial with an open-label solriamfetol period, then 1:1 randomization for patients who respond; the primary endpoint is time from randomization to relapse of depressive symptoms.

Positive

• Phase 3 initiation; first patient dosed on Feb 24, 2026
• Randomized withdrawal design with 1:1 solriamfetol versus placebo
• Primary endpoint defined as time to relapse of depressive symptoms

Negative

• No efficacy or safety results available yet; trial is ongoing
• Relapse-based primary endpoint may require extended follow-up to read out

News Market Reaction – AXSM

-2.75%

5 alerts

-2.75% News Effect

-$239M Valuation Impact

$8.45B Market Cap

1.4x Rel. Volume

On the day this news was published, AXSM declined 2.75%, reflecting a moderate negative market reaction. Our momentum scanner triggered 5 alerts that day, indicating moderate trading interest and price volatility. This price movement removed approximately $239M from the company's valuation, bringing the market cap to $8.45B at that time.

Data tracked by StockTitan Argus on the day of publication.

Key Figures

Trial phase: Phase 3 Randomization ratio: 1:1

2 metrics

Trial phase Phase 3 CLARITY solriamfetol trial in MDD with EDS

Randomization ratio 1:1 Responders randomized to continue solriamfetol or switch to placebo

Market Reality Check

Price: $163.89 Vol: Volume 845,236 is 1.58x t...

high vol

$163.89 Last Close

Volume Volume 845,236 is 1.58x the 20-day average of 535,336, indicating elevated trading activity ahead of this trial update. high

Technical Shares trade above the 200-day MA at 132.02 and sit about 8.74% below the 52-week high of 191.5.

Peers on Argus

AXSM fell about 4.88% while peers were mixed: LEGN -6.26%, RYTM -2.93%, but NUVL...

1 Down

AXSM fell about 4.88% while peers were mixed: LEGN -6.26%, RYTM -2.93%, but NUVL +2.43% and ABVX +3.6%. With peers not moving uniformly, the action appears stock-specific rather than a clean sector rotation.

Previous Clinical trial Reports

5 past events · Latest: Jan 15 (Positive)

Same Type Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Jan 15	Phase 3 initiation	Positive	-1.6%	First patient dosed in FORWARD Phase 3 AXS-14 fibromyalgia trial.
Dec 31	Regulatory milestone	Positive	+22.8%	FDA acceptance and Priority Review of sNDA for AXS-05 in Alzheimer’s agitation.
Dec 31	Regulatory milestone	Positive	+22.8%	FDA pre-NDA feedback supports AXS-12 narcolepsy NDA submission plan.
Apr 04	Pivotal data presentations	Positive	-8.4%	Positive pivotal Phase 3 AXS-05 and AXS-12 results presented at neurology meeting.
Apr 01	Topline Phase 3 data	Negative	-4.3%	PARADIGM solriamfetol MDD trial missed primary endpoint; subgroup signal in severe EDS.

Pattern Detected

Clinical and regulatory CNS updates have produced mixed reactions: some high double-digit gains on de-risking catalysts, but several positive data/initiations have seen negative or muted responses.

Recent Company History

Over the past year, Axsome’s key CNS milestones have centered on late-stage programs. FDA Priority Review and pre-NDA support for AXS-05 and AXS-12 on Dec 31, 2025 each coincided with strong positive moves, while pivotal data presentations in April 2025 and solriamfetol PARADIGM topline results triggered selloffs despite clinically important signals. The Jan 15, 2026 Phase 3 AXS-14 initiation also saw a modest decline, suggesting trial-start headlines alone have not consistently driven upside.

Historical Comparison

+6.3% avg move · Clinical-trial headlines have averaged a 6.25% move. The current CLARITY Phase 3 initiation for solr...

clinical trial

+6.3%

Average Historical Move clinical trial

Clinical-trial headlines have averaged a 6.25% move. The current CLARITY Phase 3 initiation for solriamfetol in MDD with EDS fits a pattern where trial starts can see only modest, sometimes negative, single-digit swings.

The solriamfetol program in MDD has evolved from the PARADIGM proof-of-concept data toward a more targeted Phase 3 strategy in patients with excessive daytime sleepiness.

Market Pulse Summary

This announcement advances solriamfetol into the CLARITY Phase 3 randomized withdrawal trial for maj...

Analysis

This announcement advances solriamfetol into the CLARITY Phase 3 randomized withdrawal trial for major depressive disorder with excessive daytime sleepiness, focusing on time to relapse as the primary endpoint. Historically, Axsome’s CNS pipeline updates have produced varied share reactions, with strong moves around de-risking FDA milestones and more tempered responses to trial starts. Investors may watch future readouts, regulatory interactions, and how this targeted MDD-with-EDS strategy builds on prior PARADIGM findings.

Key Terms

major depressive disorder, excessive daytime sleepiness, double-blind, placebo-controlled, +3 more

7 terms

major depressive disorder medical

"the treatment of major depressive disorder (MDD) with excessive daytime sleepiness"

A clinical condition characterized by persistent, severe low mood, loss of interest in daily activities, and reduced ability to function at work or home, lasting weeks or longer. It matters to investors because it drives demand for treatments and mental health services, affects workforce productivity and absenteeism, influences health-care and insurance costs, and shapes risks and opportunities for companies developing drugs, therapies or workplace programs—like a long-lasting storm that lowers economic output.

excessive daytime sleepiness medical

"major depressive disorder (MDD) with excessive daytime sleepiness (EDS) symptoms"

A chronic condition in which a person repeatedly struggles to stay awake or experiences overwhelming sleep episodes during normal daytime activities, not merely the occasional tiredness everyone feels. Investors care because it affects large groups of patients, drives demand for medical tests, treatments and supportive services, and shapes potential market size and healthcare spending—imagine a smartphone that keeps losing charge during the day and needs a new type of battery.

double-blind medical

"CLARITY ... is a Phase 3, double-blind, placebo-controlled, multicenter randomized withdrawal trial"

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 trial"

"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

"multicenter randomized withdrawal trial in patients with MDD with EDS symptoms"

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.

primary endpoint medical

"The primary endpoint will be the time from randomization to relapse of depressive symptoms."

The primary endpoint is the single main result a clinical study is designed to measure to decide if a treatment works, like the finish line in a race that tells you who won. Investors care because meeting or missing this goal drives regulatory decisions, future sales expectations and stock value — it turns trial data into a clear yes-or-no signal about a drug’s commercial prospects.

AI-generated analysis. Not financial advice.

NEW YORK, Feb. 24, 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 that the first patient has been dosed in the CLARITY Phase 3 trial of solriamfetol in the treatment of major depressive disorder (MDD) with excessive daytime sleepiness (EDS) symptoms.

CLARITY (Clinical Assessment of Response in the Treatment of Depression with Daytime Sleepiness Using Solriamfetol) is a Phase 3, double-blind, placebo-controlled, multicenter randomized withdrawal trial in patients with MDD with EDS symptoms consisting of an open-label solriamfetol treatment period and a randomized, double-blind treatment period. Patients achieving a treatment response during the open-label period will be randomized in a 1:1 ratio to continue solriamfetol or to switch to placebo. The primary endpoint will be the time from randomization to relapse of depressive symptoms.

About Major Depressive Disorder with Excessive Daytime Sleepiness Symptoms

Major Depressive Disorder (MDD) is a serious, common, biologically based psychiatric disorder and a leading cause of disability worldwide, impacting over 21 million adults in the U.S. alone.^1-3 It is characterized by depressed mood and loss of interest or pleasure, as well as disturbed sleep or appetite, impaired cognitive function, feelings of guilt and worthlessness, and low energy, among other symptoms. MDD can result in severe functional impairments that interfere with all aspects of life, and in severe cases, can lead to suicide.¹ Excessive daytime sleepiness (EDS) is a common symptom in individuals with MDD that affects approximately 50% of patients and is associated with a greater risk of major depressive episodes.⁴ Patients with EDS have difficulty maintaining wakefulness and exhibit an increased tendency to fall asleep during the day, including in inappropriate circumstances, resulting in impaired daily functioning and increased safety risks. There are currently no approved treatments for MDD with EDS symptoms.

About Solriamfetol

Solriamfetol is a dopamine and norepinephrine reuptake inhibitor (DNRI), TAAR1 agonist, and 5-HT_1A agonist being developed for the treatment of attention deficit hyperactivity disorder (ADHD), major depressive disorder (MDD) with excessive daytime sleepiness (EDS), binge eating disorder (BED), and excessive sleepiness associated with shift work disorder (SWD).

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. World Health Organization. Depression and Other Common Mental Disorders: Global Health Estimates. 2017.https://www.who.int/publications/i/item/depression-global-health-estimates
2. National Institute of Mental Health. Major Depression. Accessed February 2026. https://www.nimh.nih.gov/health/statistics/major-depression
3. Substance Abuse and Mental Health Services Administration. Key Substance Use and Mental Health Indicators in the United States: Results from the 2023 National Survey on Drug Use and Health. July 2024. https://www.samhsa.gov/data/report/2023-nsduh-annual-national-report
4. Hein M, et al. Prevalence and risk factors of excessive daytime sleepiness in major depression: A study with 703 individuals referred for polysomnography. J Affect Disord. 2019 Jan 15;243:23-32. https://pubmed.ncbi.nlm.nih.gov/30223136

FAQ

What is the CLARITY Phase 3 trial announced by Axsome (AXSM) on Feb 24, 2026?

CLARITY is a Phase 3, double-blind, placebo-controlled randomized withdrawal trial of solriamfetol in MDD with EDS. According to Axsome, it includes an open-label treatment period then 1:1 randomization for responders to assess relapse timing.

What milestone did Axsome (AXSM) report for the solriamfetol CLARITY trial on Feb 24, 2026?

Axsome reported dosing the first patient in CLARITY on Feb 24, 2026. According to Axsome, this marks initiation of the Phase 3 randomized withdrawal study in adults with MDD and EDS symptoms.

How is patient randomization structured in the AXSM CLARITY Phase 3 trial?

Responders in the open-label period are randomized 1:1 to continue solriamfetol or switch to placebo. According to Axsome, this randomized withdrawal design evaluates durability of treatment response versus relapse.

What is the primary endpoint of Axsome's (AXSM) CLARITY Phase 3 trial and what does it measure?

The primary endpoint is time from randomization to relapse of depressive symptoms. According to Axsome, this measures how long treatment responders maintain improvement after randomization to active drug or placebo.

Does the CLARITY announcement from Axsome (AXSM) include trial results or timelines for readout?

No, the announcement reports initiation and first patient dosing but includes no efficacy or readout timelines. According to Axsome, the study is ongoing with outcomes measured by relapse timing after randomization.

Who are the participants targeted in Axsome's (AXSM) CLARITY trial of solriamfetol?

CLARITY enrolls adults with major depressive disorder who have excessive daytime sleepiness symptoms. According to Axsome, eligible patients enter an open-label solriamfetol period and responders are randomized for double-blind evaluation.