Modeyso鈩� (dordaviprone) Included in National Comprehensive Cancer Network庐 (NCCN庐) Clinical Practice Guidelines in Oncology for H3 K27M-mutant Diffuse Glioma
Jazz Pharmaceuticals (NASDAQ: JAZZ) announced that Modeyso鈩� (dordaviprone) has been included in the NCCN Clinical Practice Guidelines as a category 2A treatment option for H3 K27M-mutant diffuse glioma. This follows the FDA's accelerated approval on August 6, 2025 for treating adult and pediatric patients with diffuse midline glioma.
Clinical trials demonstrated an overall response rate of 22% among 50 patients, with a median response duration of 10.3 months. Among responders, 73% maintained response for at least six months. Safety evaluation in 376 patients showed serious adverse reactions in 33% of cases, with common side effects including fatigue, headache, and vomiting.
Modeyso represents the first treatment option for this ultra-rare and aggressive brain tumor, marking a significant advancement in patient care.
Jazz Pharmaceuticals (NASDAQ: JAZZ) ha comunicato che Modeyso鈩� (dordaviprone) 猫 stato inserito nelle linee guida cliniche NCCN come opzione terapeutica di categoria 2A per il glioma diffuso con mutazione H3 K27M. Ci貌 segue l'approvazione accelerata da parte della FDA il 6 agosto 2025 per il trattamento di pazienti adulti e pediatrici con glioma diffuso della linea mediana.
Gli studi clinici hanno riportato un tasso di risposta globale del 22% su 50 pazienti, con una durata mediana della risposta di 10,3 mesi. Tra i pazienti che hanno risposto, il 73% ha mantenuto la risposta per almeno sei mesi. La valutazione della sicurezza su 376 pazienti ha evidenziato reazioni avverse gravi nel 33% dei casi; gli effetti collaterali pi霉 comuni sono stati affaticamento, mal di testa e vomito.
Modeyso rappresenta la prima opzione di trattamento per questo tumore cerebrale ultra鈥憆aro e aggressivo, segnando un importante progresso per la cura dei pazienti.
Jazz Pharmaceuticals (NASDAQ: JAZZ) anunci贸 que Modeyso鈩� (dordaviprone) ha sido incluido en las gu铆as de pr谩ctica cl铆nica NCCN como una opci贸n terap茅utica de categor铆a 2A para el glioma difuso con mutaci贸n H3 K27M. Esto sigue a la aprobaci贸n acelerada de la FDA el 6 de agosto de 2025 para el tratamiento de pacientes adultos y pedi谩tricos con glioma difuso de la l铆nea media.
Los ensayos cl铆nicos mostraron una tasa de respuesta global del 22% entre 50 pacientes, con una duraci贸n mediana de la respuesta de 10,3 meses. Entre los respondedores, el 73% mantuvo la respuesta durante al menos seis meses. La evaluaci贸n de seguridad en 376 pacientes indic贸 reacciones adversas graves en el 33% de los casos; los efectos secundarios m谩s frecuentes fueron fatiga, cefalea y v贸mitos.
Modeyso representa la primera opci贸n de tratamiento para este tumor cerebral ultrarraro y agresivo, suponiendo un avance significativo en la atenci贸n a los pacientes.
Jazz Pharmaceuticals (NASDAQ: JAZZ)電� Modeyso鈩�(dordaviprone)臧� NCCN 鞛勳儊歆�旃棎 H3 K27M 霃岇棸氤�鞚� 頇曥偘 甑愲靹疙彫膦�(difuse glioma)鞐� 雽�頃� 旃错厡瓿犽Μ 2A 旃橂 鞓奠厴鞙茧 韽暔霅橃棃雼り碃 氚滍憸頄堨姷雼堧嫟. 鞚措姅 靹膘澑 氚� 靻岇晞鞚� 頇曥偘 欷戧皠靹� 甑愳(diffuse midline glioma) 旃橂鞐� 雽�頃� 2025雲� 8鞗� 6鞚� FDA鞚� 臧�靻� 鞀轨澑鞚� 氚涭潃 雿� 霐半ジ 瓴冹瀰雼堧嫟.
鞛勳儊鞁滍棙鞐愳劀電� 50氇呾潣 頇橃瀽 欷� 鞝勳泊 氚橃潙毳犾澊 22%鞓赌瓿�, 氚橃潙鞚� 欷戩暀 歆�靻嶊赴臧勳潃 10.3臧滌洈鞙茧 雮橅儉雮姷雼堧嫟. 氚橃潙鞚� 氤挫澑 頇橃瀽 欷� 73%電� 鞝侅柎霃� 6臧滌洈 鞚挫儊 氚橃潙鞚� 鞙犾霅橃棃鞀惦媹雼�. 376氇呾潣 頇橃瀽毳� 雽�靸侅溂搿� 頃� 鞎堨爠靹� 韽夑皜鞐愳劀電� 33%鞐愳劀 欷戨寑頃� 鞚挫儊氚橃潙鞚� 氤搓碃霅橃棃瓿�, 頋旐暅 攵�鞛戩毄鞙茧電� 頂茧, 霊愴喌, 甑啝臧� 鞛堨棃鞀惦媹雼�.
Modeyso電� 鞚� 齑堩潿攴�頃橁碃 瓿店博鞝侅澑 雵岇鞏戩棎 雽�頃� 斓滌磮鞚� 旃橂 鞓奠厴鞙茧, 頇橃瀽 旃橂鞐� 鞛堨柎 欷戩殧頃� 歆勳爠鞚� 鞚橂頃╇媹雼�.
Jazz Pharmaceuticals (NASDAQ: JAZZ) a annonc茅 que Modeyso鈩� (dordaviprone) a 茅t茅 ajout茅 aux recommandations cliniques NCCN en tant qu鈥檕ption th茅rapeutique de cat茅gorie 2A pour le gliome diffus mut茅 H3 K27M. Ceci fait suite 脿 l鈥�approbation acc茅l茅r茅e de la FDA le 6 ao没t 2025 pour le traitement des patients adultes et p茅diatriques atteints d鈥檜n gliome diffus de la ligne m茅diane.
Les essais cliniques ont montr茅 un taux de r茅ponse global de 22% chez 50 patients, avec une dur茅e m茅diane de r茅ponse de 10,3 mois. Parmi les r茅pondeurs, 73% ont conserv茅 la r茅ponse pendant au moins six mois. L鈥櫭﹙aluation de la s茅curit茅 sur 376 patients a r茅v茅l茅 des r茅actions ind茅sirables graves chez 33% des cas; les effets secondaires fr茅quents comprenaient fatigue, c茅phal茅e et vomissements.
Modeyso repr茅sente la premi猫re option de traitement pour cette tumeur c茅r茅brale ultra鈥憆are et agressive, constituant une avanc茅e majeure pour la prise en charge des patients.
Jazz Pharmaceuticals (NASDAQ: JAZZ) gab bekannt, dass Modeyso鈩� (dordaviprone) in die NCCN-Leitlinien als Behandlungsoption der Kategorie 2A f眉r H3 K27M-mutiertes diffuses Gliom aufgenommen wurde. Dies folgt auf die beschleunigte Zulassung der FDA am 6. August 2025 zur Behandlung erwachsener und p盲diatrischer Patienten mit diffusem Mittelliniengliom.
Klinische Studien zeigten eine Gesamtansprechrate von 22% bei 50 Patienten und eine medianes Ansprechdauer von 10,3 Monaten. Unter den Ansprechern hielten 73% die Wirkung f眉r mindestens sechs Monate aufrecht. Die Sicherheitsbewertung bei 376 Patienten ergab schwere unerw眉nschte Reaktionen in 33% der F盲lle; h盲ufige Nebenwirkungen waren M眉digkeit, Kopfschmerzen und Erbrechen.
Modeyso stellt die erste Behandlungsoption f眉r diesen ultrarellen und aggressiven Hirntumor dar und markiert einen bedeutenden Fortschritt in der Patientenversorgung.
- First-ever treatment option approved for H3 K27M-mutant diffuse midline glioma
- Rapid inclusion in NCCN Guidelines following FDA approval
- 22% overall response rate in clinical trials
- 73% of responders maintained response for at least 6 months
- 10.3 months median duration of response
- Serious adverse reactions occurred in 33% of patients
- Approval is accelerated and contingent upon verification in Phase 3 trial
- Only 27% of responders maintained response for 12 months or more
Insights
Jazz's Modeyso now in NCCN guidelines represents major advancement as first-ever treatment for rare, aggressive H3 K27M-mutant brain tumors.
The inclusion of Modeyso (dordaviprone) in the NCCN Guidelines represents a significant therapeutic breakthrough for patients with H3 K27M-mutant diffuse glioma. This is particularly noteworthy as it's the first-ever treatment option for this ultra-rare and aggressive brain tumor, addressing a critical unmet need in neuro-oncology.
The data supporting Modeyso is meaningful in the context of this devastating disease. The 22% overall response rate demonstrated in the integrated efficacy analysis may seem modest by general oncology standards, but for diffuse midline gliomas, which historically have had essentially zero effective treatment options, this represents a paradigm shift. The median duration of response of 10.3 months with 73% of responders maintaining responses for at least six months is especially impressive given the typically rapid progression of these tumors.
The NCCN's rapid incorporation of Modeyso into both pediatric and adult guidelines underscores the significance of this advancement. For context, diffuse midline gliomas with the H3 K27M mutation are associated with dismal prognosis, with median survival typically measured in months rather than years. The safety profile appears manageable, with fatigue, headache, and gastrointestinal symptoms being most common - an acceptable tradeoff given the deadly nature of the disease.
While this approval is under the FDA's accelerated pathway, contingent on the Phase 3 ACTION confirmatory trial, the inclusion in NCCN Guidelines will likely drive rapid adoption as the standard of care for these patients. This represents a potential anchor point for future combination approaches and additional research in this historically treatment-resistant form of brain cancer.
The NCCN guideline inclusion for Modeyso represents a significant commercial milestone for Jazz Pharmaceuticals in the ultra-rare disease space. This rapid incorporation into treatment guidelines typically accelerates insurance coverage decisions and physician adoption, potentially shortening the usual lag between FDA approval and widespread utilization.
Jazz's strategic positioning in the rare neurological disease market is evident with this approval. The H3 K27M-mutant diffuse glioma market, while small in patient population, represents a high unmet need where first-mover advantage is particularly valuable. With no existing competition in this indication, Jazz can establish Modeyso as the foundation of care before potential competitors enter.
The accelerated approval pathway does create some uncertainty, as continued approval hinges on the Phase 3 ACTION confirmatory trial results. However, the compelling response duration data - 10.3 months median duration with 73% maintaining response for 6+ months - provides reasonable confidence in the potential for full approval.
From a market perspective, rare disease therapeutics typically command premium pricing, and as the only option for this deadly condition, Modeyso will likely follow this model. While the ultra-rare nature of H3 K27M-mutant diffuse glioma means the total addressable market is limited, the high unmet need and lack of alternatives create favorable conditions for reimbursement despite potentially high costs. This approval strengthens Jazz's specialized CNS portfolio and demonstrates their ability to successfully navigate complex regulatory pathways for challenging-to-treat conditions.
Modeyso, the first treatment option for this ultra-rare and aggressive brain tumor, is commercially available in
For
Modeyso听was granted accelerated approval by the
"The rapid addition of Modeyso to the NCCN Guidelines庐 鈥� in both the Pediatric Central Nervous System Cancers and Central Nervous System Cancers guidelines 鈥� reflects the urgency of the unmet need that patients are faced with when diagnosed with this devastating and aggressive brain tumor," said Kelvin Tan, MB BCh, MRCPCH, chief medical affairs officer听of Jazz Pharmaceuticals. "We are proud to bring Modeyso to patients in the
The NCCN Guidelines庐 play a pivotal role in decision-making processes for individuals involved in cancer care all over the world, including physicians, nurses, pharmacists, payers, and patients and their families. The guidelines present expert recommendations for cancer screening, diagnosis and treatment, as well as cancer care options, and are utilized in cancer treatment decision-making to drive positive patient outcomes. NCCN is a not-for-profit alliance of 33 leading cancer centers devoted to patient care, research and education. NCCN is dedicated to defining and advancing effective, equitable, accessible and quality cancer care and prevention so all people can live better lives. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
The听FDA approval of Modeyso 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 pre-specified 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 safety of听Modeyso听was evaluated in 376听adult and pediatric patients with glioma across four听open-label clinical studies. Serious adverse reactions occurred in
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.2,3 It is characterized by a specific genetic mutation (H3 K27M) that disrupts epigenetic regulation and drives tumor growth.4 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.5 Median survival is approximately one year from diagnosis and less than six months after disease progression following frontline therapy.5听
About Modeyso鈩⑻�(dordaviprone)听
Modeyso (dordaviprone) is approved by the
Modeyso听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 (), which is evaluating the safety and clinical benefit of Modeyso in newly diagnosed patients with H3 K27M-mutant diffuse glioma following radiotherapy.4听Modeyso听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听
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听
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听
ADVERSE REACTIONS
Serious adverse reactions occurred in
The most common adverse reactions (鈮�
DRUG INTERACTIONS听
Strong and Moderate CYP3A4 Inhibitors听
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听
Avoid concomitant use of strong and moderate CYP3A4 inducers with MODEYSO.
USE IN SPECIFIC POPULATIONS听
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听(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 鈥� 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听Dublin, Ireland听with research and development laboratories, manufacturing facilities and employees in multiple countries committed to serving patients worldwide. Please visit听www.jazzpharmaceuticals.com听for more information.
Contacts:
Media:
Kristin Bhavnani
Head of Global Corporate Communications
Jazz Pharmaceuticals plc
[email protected]
Ireland听+353 1 637 2141
Investors:
Jack Spinks
Executive Director, Investor Relations
Jazz Pharmaceuticals plc
[email protected]听
Ireland听+353 1 634 3211
1 MODEYSO (dordaviprone) Prescribing Information.
2 Yang, Z., Sun, L., Chen, et al. New progress in the treatment of diffuse midline glioma with H3K27M alteration. Heliyon. 2024;10(2).
3 National Cancer Institute. Diffuse Midline Glioma: Diagnosis and Treatment. Updated August 20, 2024. Accessed September 8, 2025.
4 ClinicalTrials.gov. ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study) (ACTION). Updated August 26, 2025. Accessed September 8, 2025.
5 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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