Jazz Pharmaceuticals Announces U.S. FDA Approval of Modeyso™ (dordaviprone) as the First and Only Treatment for Recurrent H3 K27M-mutant Diffuse Midline Glioma
Jazz Pharmaceuticals (NASDAQ: JAZZ) has achieved a groundbreaking milestone with the FDA's accelerated approval of Modeyso™ (dordaviprone), the first-ever treatment for H3 K27M-mutant diffuse midline glioma with progressive disease. This ultra-rare and aggressive brain tumor affects approximately 2,000 people annually in the U.S., primarily children and young adults.
The approval is based on clinical studies showing an overall response rate of 22% among 50 patients, with a median response duration of 10.3 months. Among responders, 73% maintained their response for at least six months. The safety evaluation, conducted across 376 patients, revealed serious adverse reactions in 33% of cases.
Modeyso, administered as a weekly oral capsule, will be commercially available in the coming weeks. Continued approval may depend on results from the Phase 3 ACTION confirmatory trial.
Jazz Pharmaceuticals (NASDAQ: JAZZ) ha raggiunto un traguardo rivoluzionario con l'approvazione accelerata della FDA per Modeyso™ (dordaviprone), il primo trattamento al mondo per il glioma diffuso della linea mediana con mutazione H3 K27M e malattia progressiva. Questo tumore cerebrale ultra-raro e aggressivo colpisce circa 2.000 persone ogni anno negli Stati Uniti, principalmente bambini e giovani adulti.
L'approvazione si basa su studi clinici che hanno mostrato un tasso di risposta complessiva del 22% su 50 pazienti, con una durata mediana della risposta di 10,3 mesi. Tra i rispondenti, il 73% ha mantenuto la risposta per almeno sei mesi. La valutazione della sicurezza, condotta su 376 pazienti, ha evidenziato reazioni avverse gravi nel 33% dei casi.
Modeyso, somministrato come capsula orale settimanale, sarà disponibile in commercio nelle prossime settimane. L'approvazione continuativa potrebbe dipendere dai risultati dello studio confermativo di Fase 3 ACTION.
Jazz Pharmaceuticals (NASDAQ: JAZZ) ha logrado un hito innovador con la aprobación acelerada de la FDA para Modeyso™ (dordaviprone), el primer tratamiento para el glioma difuso de línea media con mutación H3 K27M y enfermedad progresiva. Este tumor cerebral ultra-raro y agresivo afecta aproximadamente a 2,000 personas al año en EE. UU., principalmente niños y adultos jóvenes.
La aprobación se basa en estudios clínicos que mostraron una tasa de respuesta global del 22% entre 50 pacientes, con una duración media de la respuesta de 10.3 meses. Entre los respondedores, el 73% mantuvo la respuesta durante al menos seis meses. La evaluación de seguridad, realizada en 376 pacientes, reveló reacciones adversas graves en el 33% de los casos.
Modeyso, administrado como cápsula oral semanal, estará disponible comercialmente en las próximas semanas. La aprobación continua podría depender de los resultados del ensayo confirmatorio de fase 3 ACTION.
Jazz Pharmaceuticals (NASDAQ: JAZZ)는 FDA의 가속 승인으로 Modeyso™ (dordaviprone)를 출시하며 획기적인 이정표를 세웠습니다. 이는 진행성 질환을 가진 H3 K27M 돌연변이 확산 중간선 교모세포종에 대한 최초의 치료제입니다. 이 초희귀 및 공격적인 뇌종양은 미국에서 매년 약 2,000명의 어린이와 젊은 성인에게 영향을 미칩니다.
승인은 50명의 환자를 대상으로 한 임상 연구에서 전체 반응률 22%와 중앙 반응 지속 기간 10.3개월을 보여준 결과에 기반합니다. 반응자 중 73%는 최소 6개월 동안 반응을 유지했습니다. 376명의 환자를 대상으로 한 안전성 평가에서는 33%에서 심각한 부작용이 보고되었습니다.
Modeyso는 주간 경구 캡슐 형태로 투여되며, 향후 몇 주 내에 상업적으로 출시될 예정입니다. 지속 승인은 3상 ACTION 확증 시험 결과에 따라 결정될 수 있습니다.
Jazz Pharmaceuticals (NASDAQ : JAZZ) a franchi une étape majeure avec l'approbation accélérée par la FDA de Modeyso™ (dordaviprone), le premier traitement pour le gliome diffus de la ligne médiane mutant H3 K27M avec maladie progressive. Cette tumeur cérébrale ultra-rare et agressive touche environ 2 000 personnes par an aux États-Unis, principalement des enfants et de jeunes adultes.
Cette approbation repose sur des études cliniques montrant un taux de réponse global de 22% chez 50 patients, avec une durée médiane de réponse de 10,3 mois. Parmi les répondeurs, 73% ont maintenu leur réponse pendant au moins six mois. L'évaluation de la sécurité, réalisée sur 376 patients, a révélé des réactions indésirables graves dans 33% des cas.
Modeyso, administré sous forme de capsule orale hebdomadaire, sera disponible commercialement dans les semaines à venir. L'approbation continue pourrait dépendre des résultats de l'essai confirmatoire de phase 3 ACTION.
Jazz Pharmaceuticals (NASDAQ: JAZZ) hat einen bahnbrechenden Meilenstein erreicht mit der beschleunigten Zulassung der FDA für Modeyso™ (dordaviprone), die erste Behandlung für H3 K27M-mutierten diffusen Mittellinien-Gliom mit fortschreitender Erkrankung. Dieser ultra-rare und aggressive Hirntumor betrifft jährlich etwa 2.000 Menschen in den USA, vorwiegend Kinder und junge Erwachsene.
Die Zulassung basiert auf klinischen Studien, die eine Gesamtansprechrate von 22% bei 50 Patienten zeigten, mit einer medianen Ansprechdauer von 10,3 Monaten. Unter den Ansprechern hielten 73% ihre Reaktion mindestens sechs Monate aufrecht. Die Sicherheitsbewertung, durchgeführt bei 376 Patienten, zeigte schwere Nebenwirkungen in 33% der Fälle.
Modeyso wird als wöchentliche orale Kapsel verabreicht und wird in den kommenden Wochen kommerziell erhältlich sein. Die fortgesetzte Zulassung könnte von den Ergebnissen der Phase-3-ACTION-Bestätigungsstudie abhängen.
- First and only FDA-approved treatment for H3 K27M-mutant diffuse midline glioma
- 22% overall response rate in clinical trials
- 73% of responders maintained response for at least 6 months
- Median duration of response of 10.3 months
- Convenient oral capsule administration once weekly
- Serious adverse reactions occurred in 33% of patients
- Approval is accelerated and contingent upon Phase 3 trial results
- Limited overall response rate of 22% leaves room for improvement
- Multiple serious side effects including hydrocephalus (5%) and vomiting (4.3%)
Insights
First-ever FDA-approved therapy for rare, aggressive brain tumor shows 22% response rate with durable benefits in previously untreatable patients.
The FDA approval of Modeyso (dordaviprone) represents a genuine breakthrough in neuro-oncology. This is the first and only approved treatment for H3 K27M-mutant diffuse midline glioma, an ultra-rare brain tumor affecting approximately
The clinical data supporting this accelerated approval is noteworthy: an overall response rate of
The safety profile appears manageable, with serious adverse reactions in
It's worth emphasizing the significance of this approval: before Modeyso, patients faced a disease with no targeted therapeutic options. While this treatment doesn't represent a cure, the durable responses observed in some patients could translate to meaningful extension of life and improved quality of life. The once-weekly oral administration also offers convenience compared to traditional IV chemotherapies.
The continued approval is contingent upon verification in the Phase 3 ACTION confirmatory trial, which will provide more definitive evidence of clinical benefit. This approach follows the FDA's accelerated approval pathway, which allows earlier access to promising treatments for serious conditions with limited options while additional confirmatory data is gathered.
Modeyso is the first treatment option for this ultra-rare and aggressive brain tumor, which primarily affects children and young adults
Accelerated approval based on an overall response rate in patients with progressive disease following prior therapy
Company to host investor webcast on August 27, 2025
For
Modeyso is the first and only treatment option approved by the FDA for this ultra-rare and aggressive brain tumor that affects an estimated 2,000 people in the
"This is a major turning point in neuro-oncology," said Patrick Wen, M.D., Director, Center for Neuro-Oncology, Dana-Farber Cancer Institute and Professor of Neurology, Harvard Medical School. "For the first time, we have an FDA-approved therapy for patients with recurrent H3 K27M-mutant diffuse midline glioma. While outcomes remain challenging for many patients, the objective responses observed with dordaviprone, including durable benefit in some patients, represent a meaningful advancement. This therapy was developed with the underlying biology of the tumor in mind and introduces a new treatment option for a population with historically limited choices."
Modeyso is administered as an oral capsule once weekly. The FDA's decision was based on an integrated efficacy analysis of 50 patients with recurrent H3 K27M-mutant diffuse midline glioma, selected from five open-label clinical studies based on prespecified eligibility criteria. The overall response rate (ORR), as assessed by blinded independent central review (BICR) using Response Assessment in Neuro-Oncology (RANO) 2.0 criteria, was
"The FDA approval of Modeyso is a milestone moment for the patients and families who have long needed new options, the clinicians who have tirelessly searched for solutions, and the researchers and advocates who never gave up," said Joshua E. Allen, Ph.D., Chief Scientific Officer, Chimerix, a Jazz Pharmaceuticals Company. "We're proud to deliver precisely the kind of transformative innovation we strive for, and we congratulate our combined Chimerix and Jazz team, and the community who worked together tirelessly to bring this treatment forward. This approval not only equips clinicians with the first targeted option for this disease but also signals a meaningful shift in what patients and families can expect after diagnosis. We would like to extend our thanks to the patients, advocates, clinicians, principal investigators, scientists, regulators and partner institutions who made this possible."
"This approval represents a long-awaited treatment option for families affected by H3 K27M-mutant diffuse midline glioma," said David F. Arons, President and Chief Executive Officer of the National Brain Tumor Society. "This is a fast-moving, devastating disease that turns families' lives upside down. For years, this diagnosis has lacked an approved treatment and today, that changes. Families finally have a treatment option, and a reason to believe in more time together to make memories that might not have otherwise been possible."
The safety of Modeyso was evaluated in 376 adult and pediatric patients with glioma across four open-label clinical studies. Serious adverse reactions occurred in
About the Phase 2 Clinical Trial Program
The efficacy and safety of Modeyso were evaluated in adult and pediatric patients with glioma across five open-label, non-randomized clinical studies (ONC006, ONC013, ONC014, ONC016, and ONC018). A pre-specified integrated efficacy analysis included 50 patients with recurrent H3 K27M-mutant diffuse midline glioma who had measurable disease per Response Assessment in Neuro-Oncology (RANO) criteria. Tumor response was assessed every eight weeks by blinded independent central review (BICR). The primary efficacy endpoint was objective response rate (ORR). Safety was evaluated across four of the clinical studies.1
More information about Modeyso, the Full Prescribing Information, and Patient Information, is available here.
Investor Webcast on August 27, 2025
The company will host a webcast on August 27, 2025, at 4:30 p.m. ET / 9:30 p.m. IST to provide investors an overview of clinical data, patient need and commercialization strategy for Modeyso. The webcast will include commentary from a leading neuro-oncology expert and the company's senior management.
A live webcast of the presentation may be accessed from the Investors section of the Jazz Pharmaceuticals website at www.jazzpharmaceuticals.com. Please connect to the website prior to the start of the presentation to ensure adequate time for any software downloads that may be necessary to listen to the webcast. An archive of the webcast will be available for at least one week following the presentation on the Investors section of the company's website at www.jazzpharmaceuticals.com.
About H3 K27M-Mutant Diffuse Midline Glioma
H3 K27M-mutant diffuse midline glioma is a rare and highly aggressive brain tumor that primarily affects the midline structures of the brain and spinal cord.4,5 It is characterized by a specific genetic mutation (H3 K27M) that disrupts epigenetic regulation and drives tumor growth.6 Most commonly diagnosed in children and young adults, patients with this type of glioma often face an extremely poor prognosis, with limited therapeutic options and very low survival rates following recurrence.7 Median survival is approximately one year from diagnosis and less than six months after progressing following frontline therapy.7
About Modeyso™ (dordaviprone)
Modeyso (dordaviprone) is approved by the
Modeyso received accelerated approval based on a pre-specified integrated efficacy analysis of 50 adult and pediatric patients with recurrent H3 K27M-mutant diffuse midline glioma enrolled across five open-label clinical studies (ONC006, ONC013, ONC014, ONC016, and ONC018). Continued approval may be contingent upon verification and description of clinical benefit in the ongoing Phase 3 ACTION trial (NCT05580562), which is evaluating the safety and clinical benefit of Modeyso in newly diagnosed patients with H3 K27M-mutant diffuse glioma following radiotherapy.6 Modeyso was developed by Chimerix prior to its acquisition by Jazz Pharmaceuticals in April 2025.
Modeyso (dordaviprone) is not approved anywhere else in the world.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hypersensitivity
MODEYSO can cause severe hypersensitivity reactions.
In the pooled safety population, Grade 3 hypersensitivity reactions occurred in
Inform patients about the signs and symptoms of hypersensitivity reactions and instruct them to seek immediate medical attention if symptoms occur.
If clinically significant hypersensitivity or anaphylaxis occur, immediately interrupt MODEYSO and initiate appropriate medical treatment and supportive care. Based on the severity of the adverse reaction, temporarily interrupt or permanently discontinue MODEYSO.
QTc Interval Prolongation
MODEYSO causes concentration-dependent QTc interval prolongation, which can increase the risk for ventricular tachyarrhythmias (e.g. torsades de pointes) or sudden death.
In patients who received MODEYSO and underwent at least one post baseline ECG, QTcF increase of >60 msec compared to baseline and QTcF >500 msec occurred in
Monitor ECGs and electrolytes prior to initiation and periodically during treatment, as clinically indicated. Increase the frequency of monitoring in patients with congenital long QT syndrome, existing QTc prolongation, a history of ventricular arrhythmias, electrolyte abnormalities, heart failure, or who are taking strong or moderate CYP3A4 inhibitors.
Avoid concomitant use with other agents known to prolong the QT interval. If concomitant use cannot be avoided, increase the frequency of monitoring and separate administration of MODEYSO and QT-prolonging product.
Interrupt or reduce the dose of MODEYSO in patients who develop QT prolongation; permanently discontinue in patients with signs of life-threatening arrhythmias.
Embryo-Fetal Toxicity
MODEYSO can cause fetal harm when administered to a pregnant woman.
Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with MODEYSO and for 1 month after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with MODEYSO and for 1 month after the last dose.
ADVERSE REACTIONS
Serious adverse reactions occurred in
The most common adverse reactions (≥
DRUG INTERACTIONS
Strong and Moderate CYP3A4 Inhibitors
Avoid concomitant use of MODEYSO with strong and moderate CYP3A4 inhibitors. If concomitant use cannot be avoided, reduce the MODEYSO dose as recommended and monitor for toxicity.
Strong and Moderate CYP3A4 Inducers
Avoid concomitant use of strong and moderate CYP3A4 inducers with MODEYSO.
USE IN SPECIFIC POPULATIONS
Lactation
There are no data on the presence of MODEYSO in human milk because of the potential for serious adverse reactions from MODEYSO in breastfed children, advise women not to breastfeed during treatment with MODEYSO and for 1 week after the last dose.
Pediatric Use
The safety and effectiveness of MODEYSO have not been established in patients less than 1 year of age. Dosing has not been established for patients weighing less than 22
Please refer to the full Prescribing Information, including both Patient Information and Instructions for Use, for complete safety and administration information.
About Jazz Pharmaceuticals
Jazz Pharmaceuticals plc (Nasdaq: JAZZ) is a global biopharma company whose purpose is to innovate to transform the lives of patients and their families. We are dedicated to developing potentially life-changing medicines for people with serious diseases – often with limited or no therapeutic options. We have a diverse portfolio of marketed medicines, including leading therapies for sleep disorders and epilepsy, and a growing portfolio of cancer treatments. Our patient-focused and science-driven approach powers pioneering research and development advancements across our robust pipeline of innovative therapeutics in oncology and neuroscience. Jazz is headquartered in
Contacts:
Media:
Kristin Bhavnani
Head of Global Corporate Communications
Jazz Pharmaceuticals plc
CorporateAffairsMediaInfo@jazzpharma.com
Ireland +353 1 637 2141
Investors:
Jack Spinks
Executive Director, Investor Relations
Jazz Pharmaceuticals plc
investorinfo@jazzpharma.com
Ireland +353 1 634 3211
1 MODEYSO (dordaviprone) Prescribing Information.
2 Jazz Pharmaceuticals. ZS Epidemiology Analysis. Data on File.
3 Arrillaga-Romany, I., Lassman, A., et al. A randomized phase 3 study of ONC201 (dordaviprone) in patients with newly diagnosed H3 K27M-mutant diffuse glioma. Neuro-oncology. 2024; 26(Supplement_2), S173-S181.
4 Yang, Z., Sun, L., Chen, et al. New progress in the treatment of diffuse midline glioma with H3K27M alteration. Heliyon. 2024;10(2).
5 National Cancer Institute. Diffuse Midline Glioma: Diagnosis and Treatment. Updated August 20, 2024. Accessed July 23, 2025. https://www.cancer.gov/rare-brain-spine-tumor/tumors/diffuse-midline-gliomas
6 ClinicalTrials.gov. ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study) (ACTION). Updated June 6, 2025. Accessed July 23, 2025. Study Details | ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study) | ClinicalTrials.gov
7 Bagley, S. J., Umemura, et al. Prognostic Features of Recurrent Midline and H3 K27M-Mutant Glioma. Cancers. 2025; 17(13):2107. https://doi.org/10.3390/cancers17132107
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