Axsome Therapeutics Announces Topline Results of PARADIGM Phase 3 Proof-of-Concept Trial of Solriamfetol in Major Depressive Disorder (MDD) with and without Excessive Daytime Sleepiness (EDS)
Axsome Therapeutics (NASDAQ: AXSM) announced topline results from the PARADIGM Phase 3 proof-of-concept trial of solriamfetol in major depressive disorder (MDD). While the study did not meet its primary endpoint of statistically significant change in MADRS total score in the overall population, promising results were observed in a prespecified subgroup.
The 6-week trial included patients with severe excessive daytime sleepiness (EDS) (n=51) and without severe EDS (n=295). In the EDS subgroup, solriamfetol 300 mg showed clinically meaningful improvements compared to placebo across multiple efficacy measures, including MADRS total score, anhedonia subscale, and remission rates.
Based on these results, Axsome plans to initiate a new Phase 3 trial specifically targeting MDD patients with EDS in 2025. The condition affects approximately 50% of MDD patients, representing a significant unmet medical need with no currently approved therapies. The drug demonstrated a safety profile consistent with previous findings.
Axsome Therapeutics (NASDAQ: AXSM) ha annunciato i risultati preliminari dello studio PARADIGM di Fase 3, che ha testato il solriamfetol nel trattamento del disturbo depressivo maggiore (MDD). Sebbene lo studio non abbia raggiunto il suo obiettivo primario di un cambiamento statisticamente significativo nel punteggio totale MADRS nella popolazione complessiva, sono stati osservati risultati promettenti in un sottogruppo predefinito.
Lo studio di 6 settimane ha incluso pazienti con sonnolenza diurna eccessiva severa (EDS) (n=51) e senza EDS severa (n=295). Nel sottogruppo EDS, il solriamfetol a 300 mg ha mostrato miglioramenti clinicamente significativi rispetto al placebo in diverse misure di efficacia, inclusi il punteggio totale MADRS, la sottoscala di anedonia e i tassi di remissione.
In base a questi risultati, Axsome prevede di avviare un nuovo studio di Fase 3 specificamente rivolto ai pazienti MDD con EDS nel 2025. Questa condizione colpisce circa il 50% dei pazienti MDD, rappresentando un'importante necessità medica non soddisfatta, poiché attualmente non esistono terapie approvate. Il farmaco ha dimostrato un profilo di sicurezza coerente con i risultati precedenti.
Axsome Therapeutics (NASDAQ: AXSM) anunció los resultados preliminares del ensayo PARADIGM de Fase 3 sobre el solriamfetol en el trastorno depresivo mayor (MDD). Aunque el estudio no alcanzó su objetivo primario de un cambio estadísticamente significativo en la puntuación total de MADRS en la población general, se observaron resultados prometedores en un subgrupo predefinido.
El ensayo de 6 semanas incluyó a pacientes con somnolencia diurna excesiva severa (EDS) (n=51) y sin EDS severa (n=295). En el subgrupo de EDS, el solriamfetol de 300 mg mostró mejoras clínicamente significativas en comparación con el placebo en múltiples medidas de eficacia, incluyendo la puntuación total de MADRS, la subescala de anhedonia y las tasas de remisión.
Con base en estos resultados, Axsome planea iniciar un nuevo ensayo de Fase 3 específicamente dirigido a pacientes con MDD y EDS en 2025. Esta condición afecta aproximadamente al 50% de los pacientes con MDD, representando una necesidad médica no satisfecha, ya que actualmente no hay terapias aprobadas. El fármaco demostró un perfil de seguridad consistente con hallazgos anteriores.
Axsome Therapeutics (NASDAQ: AXSM)는 주요 우울 장애(MDD)에서 솔리암페톨의 PARADIGM 3상 개념 증명 시험의 주요 결과를 발표했습니다. 연구는 전체 인구에서 MADRS 총점의 통계적으로 유의미한 변화라는 주요 목표를 달성하지 못했지만, 사전 정의된 하위 그룹에서 유망한 결과가 관찰되었습니다.
6주간의 시험은 심각한 주간 과다 졸림(EDS) 환자(n=51)와 심각한 EDS가 없는 환자(n=295)를 포함했습니다. EDS 하위 그룹에서 300mg의 솔리암페톨은 MADRS 총점, 무쾌감 하위 척도 및 완화 비율을 포함한 여러 효능 측정에서 위약에 비해 임상적으로 의미 있는 개선을 보였습니다.
이 결과를 바탕으로 Axsome은 2025년에 EDS가 있는 MDD 환자를 대상으로 하는 새로운 3상 시험을 시작할 계획입니다. 이 상태는 MDD 환자의 약 50%에 영향을 미치며, 현재 승인된 치료법이 없는 중요한 unmet medical need를 나타냅니다. 이 약물은 이전 연구 결과와 일치하는 안전성 프로필을 보여주었습니다.
Axsome Therapeutics (NASDAQ: AXSM) a annoncé les résultats préliminaires de l'essai PARADIGM de Phase 3 sur le solriamfetol dans le trouble dépressif majeur (MDD). Bien que l'étude n'ait pas atteint son objectif principal d'un changement statistiquement significatif du score total MADRS dans la population générale, des résultats prometteurs ont été observés dans un sous-groupe prédéfini.
L'essai de 6 semaines a inclus des patients souffrant de somnolence diurne excessive sévère (EDS) (n=51) et sans EDS sévère (n=295). Dans le sous-groupe EDS, le solriamfetol à 300 mg a montré des améliorations cliniquement significatives par rapport au placebo sur plusieurs mesures d'efficacité, y compris le score total MADRS, la sous-échelle d'anhedonie et les taux de rémission.
Sur la base de ces résultats, Axsome prévoit de lancer un nouvel essai de Phase 3 spécifiquement destiné aux patients MDD souffrant d'EDS en 2025. Cette condition affecte environ 50 % des patients MDD, représentant un besoin médical non satisfait important, car il n'existe actuellement aucune thérapie approuvée. Le médicament a démontré un profil de sécurité conforme aux résultats précédents.
Axsome Therapeutics (NASDAQ: AXSM) hat die vorläufigen Ergebnisse der PARADIGM Phase-3-Studie zu Solriamfetol bei Major Depressive Disorder (MDD) bekannt gegeben. Obwohl die Studie ihr primäres Ziel einer statistisch signifikanten Veränderung der MADRS-Gesamtpunktzahl in der Gesamtpopulation nicht erreicht hat, wurden vielversprechende Ergebnisse in einer vordefinierten Untergruppe beobachtet.
Die 6-wöchige Studie umfasste Patienten mit schwerer übermäßiger Tagesmüdigkeit (EDS) (n=51) und ohne schwere EDS (n=295). In der EDS-Untergruppe zeigte Solriamfetol 300 mg klinisch bedeutsame Verbesserungen im Vergleich zu Placebo über mehrere Wirksamkeitsmaße, einschließlich der MADRS-Gesamtpunktzahl, der Anhedonie-Skala und der Remissionsraten.
Basierend auf diesen Ergebnissen plant Axsome, 2025 eine neue Phase-3-Studie speziell für MDD-Patienten mit EDS zu starten. Diese Erkrankung betrifft etwa 50 % der MDD-Patienten und stellt einen erheblichen ungedeckten medizinischen Bedarf dar, da derzeit keine zugelassenen Therapien existieren. Das Medikament zeigte ein Sicherheitsprofil, das mit früheren Ergebnissen übereinstimmt.
- Promising efficacy in MDD patients with severe EDS subgroup
- Clear path forward with planned Phase 3 trial in 2025
- Favorable safety profile consistent with previous findings
- Large market opportunity with 50% of MDD patients affected by EDS
- No current approved therapies for MDD with EDS
- Failed to meet primary endpoint in overall patient population
- Small sample size in EDS subgroup (n=51)
- Study not powered for statistical significance in subgroups
Insights
Axsome's PARADIGM trial results represent a classic case of therapeutic target refinement in CNS drug development. While solriamfetol failed to demonstrate statistical significance on the primary MADRS endpoint in the overall MDD population, the prespecified subgroup analysis revealed a potentially valuable signal in patients with concomitant severe excessive daytime sleepiness (EDS).
The pharmacological rationale aligns with these findings. Solriamfetol, a dopamine and norepinephrine reuptake inhibitor, improves wakefulness but isn't a broad-spectrum antidepressant. The preferential response in the EDS subgroup (n=51) suggests a mechanistically coherent approach targeting a specific symptom domain that affects approximately
The multiple efficacy measures showing improvement in the EDS subpopulation (MADRS total score, anhedonia subscale, remission rates, CGI-S, CGI-I, and PGI-I) provide consistent directional support despite the study not being powered for subgroup statistical significance. The clean safety profile, consistent with solriamfetol's established profile, provides a favorable risk-benefit proposition for continued development.
This pivot to MDD with EDS represents a rational development strategy addressing an unmet need—no approved therapies currently target this specific symptom cluster. The planned Phase 3 trial in 2025 will need to demonstrate not just statistical significance but clinically meaningful improvements to establish solriamfetol as a differentiated treatment option in the competitive MDD landscape.
Axsome's solriamfetol trial results exemplify the evolving precision medicine approach in psychiatry. The primary endpoint miss in the general MDD population is balanced by encouraging signals in the EDS subgroup, creating a narrower but potentially viable commercial pathway.
From a market opportunity perspective, the
The trial design demographics are notable—only 51 patients had severe EDS versus 295 without—suggesting the company didn't initially anticipate the stratified response pattern. The decision to advance into Phase 3 specifically for MDD with EDS demonstrates pipeline management agility, salvaging value from what could otherwise be viewed as a failed program.
For Axsome's broader CNS portfolio strategy, this represents a complementary approach to their existing MDD medication Auvelity. Rather than competing with their own product, solriamfetol could address a differentiated patient subtype, potentially expanding their overall MDD market penetration through symptom-specific targeting.
Investors should view this as a strategic refocusing rather than a clear success or failure. The next Phase 3 trial in the targeted population will be the true determinant of commercial potential, with execution timeline and trial design being key variables to monitor.
Results support continued development in MDD with concomitant EDS; Phase 3 trial planned in 2025
Approximately 50 percent of MDD patients experience EDS1, highlighting high unmet need
NEW YORK, April 01, 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 results of the PARADIGM Phase 3 proof-of-concept trial of solriamfetol in major depressive disorder (MDD) with and without severe excessive daytime sleepiness (EDS). In the overall patient population, the study did not demonstrate a statistically significant change on the Montgomery-Åsberg Depression Rating Scale (MADRS) total score compared to placebo, the study’s primary endpoint. In the prespecified subgroup of patients with severe EDS, treatment with solriamfetol resulted in greater improvements in depressive symptoms compared to placebo. The study was not powered to demonstrate statistical significance in the prespecified subgroups. Based on the results in the EDS subgroup, Axsome plans to initiate a Phase 3 trial in MDD patients with EDS in 2025.
The PARADIGM study was a 6-week, randomized, double-blind, placebo-controlled, multicenter, U.S. trial, in which MDD patients with severe EDS (n=51) and without severe EDS (n=295) were randomized to treatment with solriamfetol 300 mg or placebo. EDS was assessed using the Epworth Sleepiness Scale (ESS). In MDD patients with severe EDS (ESS score ≥16), solriamfetol treatment resulted in clinically meaningful and numerically greater improvements compared to placebo on multiple efficacy measures including MADRS total score, MADRS anhedonia subscale, MADRS remission (total score ≤10), Clinical Global Impression of Severity (CGI-S), Clinical Global Impression of Improvement (CGI-I), and Patient Global Impression of Improvement (PGI-I), at Week 6. In patients without severe EDS, there was no meaningful difference as compared to placebo on the study endpoints.
EDS is a common symptom in patients with MDD and has a reported prevalence of approximately
Herriot Tabuteau, MD, Chief Executive Officer of Axsome Therapeutics, said, “We are pleased to have completed the PARADIGM trial which provides data on the potential utility of solriamfetol in patients with MDD. The promising results with solriamfetol in MDD patients with severe EDS align with its known pharmacology and support its further evaluation in this potentially new indication. We plan to initiate a Phase 3 trial in MDD with EDS 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.
Full results will be presented at future scientific conferences.
About Major Depressive Disorder
Major Depressive Disorder (MDD) is a serious, common, biologically based disorder 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.2 According to the World Health Organization (WHO), depression is the leading cause of disability worldwide, and one of the leading contributors to the global burden of disease. Approximately 21 million adults in the U.S. are affected by MDD each year,3 and approximately two-thirds of patients experience inadequate response with first-line treatment.4
About Solriamfetol
Solriamfetol is a dopamine and norepinephrine reuptake inhibitor (DNRI), TAAR1 agonist, and 5-HT1A 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 circumstance.
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
- Hein M, Lanquart JP, Loas G, Hubain P, Linkowski P. 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.
- World Health Organization. Depressive disorder (depression). Accessed March 2025.
- National Institute of Mental Health. Major Depression. Accessed March 2025.
- Rush AJ et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905-17.
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