Axsome Therapeutics Announces FOCUS Phase 3 Trial of Solriamfetol in Adults with Attention Deficit Hyperactivity Disorder (ADHD) Achieves Primary Endpoint

Rhea-AI Summary

Axsome Therapeutics (NASDAQ: AXSM) announced positive results from its FOCUS Phase 3 trial of solriamfetol for treating Attention Deficit Hyperactivity Disorder (ADHD). The trial, involving 516 adults, demonstrated statistically significant improvements in ADHD symptoms compared to placebo.

Key findings include:

• 17.7-point reduction in AISRS total score with 150mg solriamfetol vs 14.3 points for placebo (p=0.039)
• 45% mean reduction in ADHD symptoms from baseline at Week 6
• 53.5% of patients on 150mg achieved clinical response vs 41.3% on placebo
• Onset of action observed as early as Week 1
• Significant reduction in disease severity (CGI-S score)

The 300mg dose showed numerically superior results compared to placebo but wasn't statistically significant. The drug was well-tolerated with no serious adverse events reported. Axsome plans to initiate pediatric trials this year.

Positive

• Achieved primary endpoint with statistically significant improvement in ADHD symptoms
• High clinical response rate: 53.5% vs 41.3% placebo
• Rapid onset of action (Week 1)
• Well-tolerated safety profile with no serious adverse events
• Clear path forward with planned pediatric trials

Negative

• 300mg dose failed to achieve statistical significance
• to adult population currently
• Dose-dependent adverse events reported

Insights

Pharmaceutical Analyst

Axsome's FOCUS Phase 3 trial results represent a significant clinical milestone for the company's CNS portfolio. The trial demonstrated that solriamfetol at 150mg produced a 45% mean reduction in ADHD symptoms from baseline, with statistically significant improvements over placebo (p=0.039) on the AISRS total score. This primary endpoint achievement is reinforced by multiple supporting outcomes, including significant reductions in disease severity (CGI-S score, p=0.017) and higher clinical response rates (53.5% vs 41.3% for placebo).

Particularly noteworthy is the rapid onset of action observed at Week 1, which provides a competitive advantage in a therapeutic area where speed of symptom relief is clinically valuable. The safety profile appears consistent with solriamfetol's established profile, with no serious adverse events reported - a critical consideration for ADHD medications.

The strategic implications are substantial as this represents potential label expansion for solriamfetol, which is already marketed as Sunosi for other indications. This approach typically carries lower development risk and cost compared to novel compounds. The planned expansion into pediatric studies further demonstrates Axsome's commitment to maximizing the commercial potential across the full ADHD patient spectrum.

While the 300mg dose showed only numerical superiority without statistical significance, this doesn't undermine the positive outcome at the 150mg dose, and may actually simplify dosing recommendations in a future regulatory submission.

Psychiatry Specialist

The FOCUS trial results demonstrate meaningful clinical efficacy for solriamfetol in adult ADHD, addressing a condition that substantially impairs functioning across multiple domains. The 45% reduction in ADHD symptoms represents a clinically significant improvement that would be meaningful to patients in real-world settings.

From a clinical perspective, the dual impact on both ADHD symptoms and overall disease severity is particularly valuable. The statistically significant improvement on the CGI-S scale indicates that the symptom reductions translate to meaningful improvements in patients' overall clinical presentation.

The 53.5% response rate (defined as ≥30% improvement) at the 150mg dose provides a clear benchmark of clinical efficacy. Early onset of action at Week 1 is therapeutically advantageous, as rapid symptom control is a priority for many ADHD patients struggling with daily functioning.

The favorable safety and tolerability profile is especially important in ADHD treatment, where medication adherence is often challenging and side effect burden can lead to discontinuation. Having additional non-stimulant treatment options with different mechanisms of action is valuable for individualizing therapy, particularly for patients who don't respond adequately to or cannot tolerate existing treatments.

These results support solriamfetol as a potentially important addition to the ADHD treatment armamentarium, offering clinicians another evidence-based option for addressing this heterogeneous and prevalent condition.

Demonstrated substantial and statistically significant improvement in ADHD symptoms as measured by the AISRS total score compared to placebo (p=0.039, primary endpoint, 150 mg solriamfetol)

Statistically significant reduction in overall ADHD disease severity as measured by the CGI-S score compared to placebo (p=0.017, key secondary endpoint, 150 mg solriamfetol)

Statistically significant rate of clinical response on the AISRS compared to placebo (p=0.024, 150 mg solriamfetol)

Onset of action as early as Week 1 compared to placebo (p=0.036, AISRS, 150 mg solriamfetol)

Well tolerated with safety profile generally consistent with prior solriamfetol trials

NEW YORK, March 25, 2025 (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 FOCUS Phase 3 trial of solriamfetol in the treatment of attention deficit hyperactivity disorder (ADHD) achieved its primary and key secondary endpoints demonstrating statistically significant improvements in ADHD symptoms and disease severity with solriamfetol compared to placebo. The FOCUS study was a randomized, double-blind, placebo-controlled, multicenter, U.S. trial, in which 516 adults with ADHD were randomized to receive solriamfetol 150 mg, solriamfetol 300 mg, or placebo, once daily, for 6 weeks.

The study achieved the primary endpoint by demonstrating a statistically significant reduction in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score compared to placebo at Week 6, with mean reductions from baseline of 17.7 points for solriamfetol 150 mg and 14.3 points for placebo (p=0.039). Overall, the improvement with solriamfetol at Week 6 represents a 45% mean reduction from baseline in ADHD symptoms. Improvements in the AISRS total score were greater with solriamfetol compared to placebo starting at Week 1 (p=0.036). Clinical response, defined as ≥30% improvement from baseline in the AISRS total score, was achieved by a statistically significantly greater percentage of patients treated with solriamfetol 150 mg (53.5%) compared to those treated with placebo (41.3%) at Week 6 (p=0.024).

The study also achieved the key secondary endpoint by statistically significantly reducing overall ADHD disease severity compared to placebo, as assessed by the Clinical Global Impression of Severity (CGI-S) for ADHD, at Week 6 (p=0.017). Results on the primary and key secondary endpoints for the exploratory 300 mg solriamfetol dose were numerically superior compared to placebo but were not statistically significant.

Gregory Mattingly, M.D., Associate Clinical Professor of Psychiatry at the Washington University School of Medicine and President of the American Professional Society for ADHD and Related Disorders, commented, “ADHD substantially impairs social, academic, and occupational functioning, while negatively impacting patient quality of life and increasing the risk of morbidity and mortality. The results of the FOCUS trial demonstrate that solriamfetol was able to reduce mean ADHD symptom burden by nearly fifty percent, which contributed to significant reductions in disease severity. These results are especially promising as part of a comprehensive wellness plan for individuals with ADHD. The symptom improvements observed with solriamfetol were accompanied by a favorable safety and tolerability profile. Based on these compelling data, solriamfetol has the potential to be an important new treatment option for adult patients living with ADHD.”

Herriot Tabuteau, MD, Chief Executive Officer of Axsome, said, “We are pleased with the positive results of the FOCUS trial which provide the first evidence from a multicenter controlled trial of the efficacy of solriamfetol in the treatment of ADHD. ADHD is a serious, heterogenous, and prevalent condition. We look forward to advancing the development of solriamfetol as a new, differentiated potential treatment for the millions of patients living ADHD. With these results in the adult population in hand, we plan to initiate a trial in pediatric patients this year.”

Solriamfetol was safe and well tolerated in the trial, with a side effect profile that was consistent with the established safety profile of solriamfetol. Rates of adverse events were dose dependent. There were no serious adverse events reported in the trial.

About the FOCUS Trial

FOCUS (Forward Treatment of Attention Deficit and Hyperactivity Using Solriamfetol) was a Phase 3, randomized, double-blind, placebo-controlled, multicenter, 6-week, parallel group trial to evaluate the efficacy and safety of solriamfetol in adults with ADHD in the United States. A total of 516 adult patients with a primary diagnosis of ADHD were randomized 1:1:1 to treatment with solriamfetol 150 mg, solriamfetol 300 mg, or placebo, once daily for 6 weeks. The primary endpoint was the change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score at Week 6. Total scores on the AISRS range from 0 to 54, with 0 corresponding to total absence of symptoms and higher scores corresponding to greater symptom severity. Mean baseline AISRS total scores for the solriamfetol 150 mg, solriamfetol 300 mg, and placebo groups were 39.1, 38.3, and 37.9 respectively. The key secondary endpoint was the change from baseline in the Clinical Global Impression of Severity (CGI-S) for ADHD at Week 6.

About Attention Deficit Hyperactivity Disorder

Attention deficit hyperactivity disorder (ADHD) is a chronic neurobiological and developmental disorder characterized by a persistent pattern of inattention, hyperactivity, or impulsivity, that interferes with functioning or development.¹ Impairments in cognition are apparent in attention, planning and problem solving, working memory, and behavioral inhibition.^2,3 An estimated 15.5 million adults and 7 million children in the U.S. are affected by ADHD,^4,5 with approximately two-thirds or more of children with ADHD continuing to experience symptoms into adulthood.⁶ The total annual societal excess cost associated with adult ADHD in the U.S. has been estimated at over $120 billion.⁷

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), 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.

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 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:
Mark Jacobson
Chief Operating Officer
(212) 332-3243
mjacobson@axsome.com

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

References

1. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 5 ed., Arlington, VA: American Psychiatric Publishing, 2013.
2. Brown TE. ADD/ADHD and Impaired Executive Function in Clinical Practice. Curr Psychiatry Rep. 2008 Oct;10(5):407-11.
3. Nestler E., Hyman S., and Malenka R. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience, Second Edition, 2^nd ed., New York: McGraw-Hill Professional, 2008.
4. Facts About ADHD in Adults. CDC. 2024.
5. Data and Statistics on ADHD. CDC. 2024.
6. Sibley MH et al. Variable Patterns of Remission From ADHD in the Multimodal Treatment Study of ADHD. Am J Psychiatry. 2022 Feb;179(2):142-151.
7. Schein J et al. Economic burden of attention-deficit/hyperactivity disorder among adults in the United States: a societal perspective. J Manag Care Spec Pharm. 2022 Feb;28(2):168-179.
   

FAQ

What were the primary results of Axsome's (AXSM) FOCUS Phase 3 trial for ADHD?

The trial showed a 17.7-point reduction in AISRS score with 150mg solriamfetol vs 14.3 for placebo (p=0.039), representing a 45% reduction in ADHD symptoms from baseline at Week 6.

How many patients achieved clinical response in AXSM's ADHD trial?

53.5% of patients on 150mg solriamfetol achieved clinical response (≥30% improvement) compared to 41.3% on placebo at Week 6 (p=0.024).

When did Axsome's (AXSM) solriamfetol show effectiveness in the ADHD trial?

Improvements were observed as early as Week 1 of treatment (p=0.036) and continued through the 6-week trial period.

What are Axsome's (AXSM) next steps for solriamfetol in ADHD treatment?

Axsome plans to initiate trials in pediatric ADHD patients in 2025.