Presentations showcase Phase 3 ACTION trial progress and continued development of novel therapies for rare brain cancers
For U.S. media and investors only
DUBLIN, Nov. 2, 2026 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced that clinical and preclinical research from its neuro-oncology portfolio will be presented at the upcoming 2026 Society for Neuro-Oncology (SNO) Annual Meeting, taking place November 12-15 in Philadelphia.
Key highlights include:
- The confirmatory Phase 3 ACTION trial evaluating Modeyso® (dordaviprone), formerly ONC201, continues to advance. In the trial, patients with newly diagnosed H3 K27M-mutant diffuse glioma who have completed standard frontline radiotherapy are randomized 1:1:1 to receive placebo, once-weekly dordaviprone, or twice-weekly dordaviprone on two consecutive days. The primary efficacy endpoint is overall survival.
- A Phase 2 clinical trial for JZP3507 (formerly ONC206) has been initiated in recurrent meningioma, the most common form of primary central nervous system cancer in adults. JZP3507 is a dual targeted investigational therapy that is an agonist of the mitochondrial protease ClpP and an antagonist of the G protein-coupled receptor DRD2.
- An oral presentation for JZP3507 will show new preclinical findings characterizing the anti-cancer activity in H3 G34-mutant glioma. JZP3507 demonstrated nanomolar potency in cell lines and patient-derived cells, as well as a ClpP-dependent mechanism underlying its anti-cancer effects.
"The data being presented at SNO demonstrates Jazz's expanding commitment to scientific innovation and our progress to develop new therapies for patients facing rare and highly aggressive brain cancers," said Josh Allen, Ph.D., chief scientific officer, oncology, Jazz Pharmaceuticals. "Building on the landmark approval of Modeyso, we are advancing the Phase 3 ACTION trial, with an interim analysis in the first half of 2027, to potentially bring this therapy to patients earlier in the disease course."
Presentations at SNO 2026 include:
Presentation Title | Authors | Presentation Details |
ACTION trial update: A randomized phase 3 study of dordaviprone (ONC201) in patients with newly diagnosed H3 K27M-mutant diffuse glioma | Arrillaga-Romany I*, Chang JH, Pellerino A, Brazil L, Cappellano A, McBain C, Lombardi G, Cardoso A, Dahlrot RH, Carceller F, Gironés Sarrió R, Pavon-Mengual M, Bhatia A, Allen J, Melemed A, Mayo C, Tarapore R, Wen P, Cloughesy T | Type: Poster presentation Location: Exhibit Hall D & E, Second Floor, Pennsylvania Convention Center Date: Friday, November 13, 7:30-9:30 p.m. ET Number: TIP-11 |
A phase 2 study to investigate the efficacy and safety of JZP3507 (formerly ONC206) in adults with recurrent grade 2 or 3 meningioma | Ramage S*, Arrillaga-Romany I, Barbaro M, Gatson N, Johnson M, Kurz S, Mendez J, Odia Y, Sharma A, Umemura Y, Wen P, Mayo C, Shonka N | Type: Poster presentation Location: Exhibit Hall D & E, Second Floor, Pennsylvania Convention Center Date: Friday, November 13, 7:30-9:30 p.m. ET Number: TIP-12 |
Allosteric ClpP agonist ONC206 alters mitochondrial metabolism to elicit anti-cancer efficacy in H3 G34-mutant glioma | Prabhu V*, Lee A, Maranto C, Foster S, Allen J | Type: Oral presentation Date: Saturday, November 14, 2:30-3:30pm ET Location: 120 ABC, First Floor, Pennsylvania Convention Center Number: EXTH-15 |
EGFR signaling drives mesenchymal cell-state transition and therapeutic vulnerability in H3K27M-mutant Diffuse Midline Glioma | Ji S, Doherty R, Pearson A*, Wink K, Lau B, Murthy B, Mota M, Natarajan S, de la Nava D, Sajjakulnukit P, Adam T, Niculcea M, Vo K, Bavani S, Yadavalli S, Cruz A, Li F, Knowles T, Phillips J, Vo T, Liu I, Kumar P, McThenia S, Mazewski C, Pytel N, Bowers D, Green A, Lyssiotis C, Qin T, Solomon D, Beck A, Nuechterlein N, Agnihotri S, Toll S, Dun M, Venneti S, Mueller S, Nazarian J, Waszak S, Koschmann C | Type: Pediatric Oral Abstracts Session I Date: Saturday, November 14, 3:45-4:45pm ET Location: 120 ABC, First Floor, Pennsylvania Convention Center Number: CSIG-09 |
Spatial Architecture of H3 K27M-mutant Diffuse Midline Glioma Reveals Prognostic Niches in Patients from the PNOC022 Clinical Trial | Savary C*, Vo T, Jackson E, Persson M, Dubois O, Douglas A, McEwen H, McLachlan T, Kline C, Franson A, Valvi S, van der Lugt J, Nazarian J, Waszak S, Koschmann C, Gupta N, Mueller S, Dun M | Type: CNS Rare Tumor Oral Abstracts Session I Date: Friday, November 13, 2:30-3:30pm ET Location: 119 AB, First Floor, Pennsylvania Convention Center Number: BIOM-72 |
Leveraging the immunomodulatory effects of dordaviprone to induce adaptive immune surveillance in diffuse midline glioma | Persson M*, Savary C, Jackson E, Duchatel R, Vo T, Dubois O, Loughnan O, Findlay I, Douglas A, Bramberger L, de la Nava D, McEwen H, Beitaki T, Mannan A, Jayaraman R, Thomas B, Rodriguez de la Fuente L, Colino-Sanguino Y, Valdes Mora F, Faridi P, Holst J, Mayall J, Kline C, Franson A, Venneti V, Hondermarck H, Horvat J, Pearson A, Ji S, Nazarian J, Hulleman E, Mueller S, Vitanza N, Koschmann C, Alonso M, Carvalheiro T, van der Lugt J, Dun M | Type: Rapid Orals Session VI A Poster Session Date: Friday, November 13, 11:30am-12:30pm ET Friday, November 13, 7:30-9:30pm ET Location: Exhibit Hall D & E, Second Floor, Pennsylvania Convention Center Number: TMIC-98 |
Exploiting Tumor Stress and Innate Immunity: ONC201 Enhances NK Cell Therapy for Pediatric Diffuse Midline Gliomas | Cheng D, Zhang P, Basar R, Shanley M, Singh A, Swaminathan J, Shrestha R, Siddaway R, Vadivel AA, Sharma A, Yang Y, Anjier A, Maegawa S, Feng S, Gordon N, Daw N, Gorlick R, Tarapore R, Prabhu V, Allen J, Koul D, Hawkins C, Zaky W, Wintermark M, Rezvani K, Gopalakrishnan V* | Type: Poster Session Date: Friday, November 13, 7:30-9:30pm ET Location: Exhibit Hall D & E, Second Floor, Pennsylvania Convention Center Number: EXTH-26 |
In vitro and in vivo evaluation of CT-179 in combination with ONC201 and ONC206 in patient-derived models of diffuse midline glioma | Mizoguchi S, Yu J, Kritzer B, Laternser S, Stein G, Kesari S, Packer P, Nazarian J, Yadavilli S* | Type: Poster Session Date: Friday, November 13, 7:30-9:30pm ET Location: Exhibit Hall D & E, Second Floor, Philadelphia Convention Center Number: EXTH-33 |
* Presenting author | ||
About Modeyso® (dordaviprone)
Modeyso (dordaviprone) is approved by FDA for the treatment of adult and pediatric patients 1 year of age and older with diffuse midline glioma harboring an H3 K27M mutation with progressive disease following prior therapy.1 Modeyso is an orally administered small molecule given once weekly. Modeyso is a protease activator of the mitochondrial ClpP and also inhibits DRD2. In vitro, dordaviprone activates the integrated stress response, induces apoptosis, and alters mitochondrial metabolism, leading to restored histone H3 K27 trimethylation in H3 K27M-mutant diffuse glioma.1
Modeyso received accelerated approval based on overall response rate and duration of response derived from 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). Full approval for this indication is contingent upon us satisfying post-marketing requirements, including the verification and description of clinical benefit in the Phase 3 ACTION confirmatory trial and other applicable post-marketing commitments. The FDA granted dordaviprone Rare Pediatric Disease designation and Fast-Track designation, and dordaviprone received Orphan Drug Designation in the United States, Europe and Australia. Modeyso was developed by Chimerix prior to its acquisition by Jazz Pharmaceuticals in April 2025.
Modeyso (dordaviprone) is approved in the United States and Japan. It 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 0.3% of patients receiving MODEYSO. Signs and symptoms of hypersensitivity may include rash, hives, fever, low blood pressure, wheezing, or swelling of the face or throat.
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 6% and 1.2% of patients, respectively.
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 33% of the 376 patients who received MODEYSO. Serious adverse reactions in >2% of patients included hydrocephalus (5%), vomiting (4.3%), headache (3.2%), seizure (2.4%), and muscular weakness (2.1%). Fatal adverse reactions occurred in 1% of patients who received MODEYSO, including cardiac arrest (0.5%), intracranial hemorrhage (0.3%), and encephalopathy (0.3%).
The most common adverse reactions (≥20%) reported in clinical trials with MODEYSO were fatigue (34%), headache (32%), vomiting (24%), nausea (24%), and musculoskeletal pain (20%). The most common (≥2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes (7%), decreased calcium (2.7%), and increased alanine aminotransferase (2.4%).
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 pounds (10 kg).
Please refer to the full Prescribing Information, including both Patient Information and Instructions for Use, for complete safety and administration information.
The full U.S. Prescribing Information for MODEYSO is available at: https://pp.jazzpharma.com/pi/modeyso.en.USPI.pdf
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 life-changing medicines for people with rare disease – often with limited or no therapeutic options. We have a diverse portfolio of medicines, including leading therapies addressing epilepsies, cancers and sleep disorders. Our patient-focused and science-driven approach powers pioneering research and development advancements across our robust pipeline of innovative therapeutics. Jazz is headquartered in Dublin, Ireland with research and development laboratories, manufacturing facilities and employees in multiple countries committed to serving patients worldwide. Please visit www.jazzpharmaceuticals.com for more information.
Contacts:
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Ireland +353 1 637 2141
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Investor:
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Ireland +353 1 634 7800
U.S. +1 650 496 2717
1 MODEYSO (dordaviprone) Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc.
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