Overview

Dordaviprone (ONC-201) is under investigation in clinical trial NCT03394027 (ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma).

Indication

No indication information available.

Associated Conditions

No associated conditions information available.

Research Report

Published: Sep 7, 2025

Dordaviprone (Modeyso): A Comprehensive Monograph on a First-in-Class Therapy for H3 K27M-Mutant Diffuse Midline Glioma

1.0 Executive Summary & Introduction to Dordaviprone

1.1 Overview of Dordaviprone: A Landmark Approval for a High Unmet Need

On August 6, 2025, the United States Food and Drug Administration (FDA) granted accelerated approval to dordaviprone, an event that represents a significant milestone in the field of neuro-oncology.[1] Marketed under the brand name Modeyso and developed by Jazz Pharmaceuticals, dordaviprone is a first-in-class, orally administered small molecule protease activator.[1] This approval establishes dordaviprone as the first and only systemic therapy specifically indicated for the treatment of adult and pediatric patients, aged one year and older, with diffuse midline glioma (DMG) harboring a histone 3 (H3) K27M mutation whose disease has progressed following prior therapy.[1]

The approval of dordaviprone, formerly known by its investigational code ONC201, is the culmination of a developmental journey that began with its discovery by Oncoceutics, followed by acquisition by Chimerix, and ultimately by Jazz Pharmaceuticals.[5] This regulatory decision was met with considerable enthusiasm from the clinical community, with leading experts describing it as a "major turning point in neuro-oncology".[3] For decades, the therapeutic landscape for this devastating central nervous system (CNS) malignancy had remained stagnant, with radiation therapy being the only established standard of care and no approved systemic options available for patients with recurrent or progressive disease.[6] The availability of dordaviprone provides a long-awaited, targeted treatment option for a patient population with a dire prognosis and historically limited therapeutic avenues.[3]

Continue reading the full research report

Clinical Trials

Title	Posted	Study ID	Phase	Status	Sponsor
A Study of ONC201 for Refractory Meningioma	2023/08/28	NCT06012929	Phase 2	Suspended	University of Nebraska
Testing for Safety and Colorectal Cancer Preventive Effects of ONC201	2022/11/30	NCT05630794	Phase 1	Recruiting	National Cancer Institute (NCI)
ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study)	2022/10/14	NCT05580562	Phase 3	Recruiting	Chimerix
ONC201 and Atezolizumab in Obesity-Driven Endometrial Cancer	2022/09/15	NCT05542407	Phase 1	Recruiting	UNC Lineberger Comprehensive Cancer Center
Biological Medicine for Diffuse Intrinsic Pontine Glioma (DIPG) Eradication 2.0	2022/07/27	NCT05476939	Phase 3	Recruiting	Gustave Roussy, Cancer Campus, Grand Paris
Expanded Access Use of ONC201 in a Patient With Diffuse Intrinsic Pontine Gliomas	2022/05/26	NCT05392374	N/A	NO_LONGER_AVAILABLE	Chimerix
Combination Therapy for the Treatment of Diffuse Midline Gliomas	2021/08/18	NCT05009992	Phase 2	Recruiting	University of California, San Francisco
A Phase II, Open Label Study of ONC201 in Adults With EGFR-low Glioblastoma	2020/11/16	NCT04629209	Phase 2	Withdrawn	Masonic Cancer Center, University of Minnesota
ONC-201 Maintenance Therapy in Acute Myeloid Leukemia and Myelodysplastic Syndrome After Stem Cell Transplant	2019/05/01	NCT03932643	Phase 1	Active, not recruiting	University of Nebraska
Ixazomib, ONC201, and Dexamethasone in Relapsed/Refractory Multiple Myeloma	2018/04/10	NCT03492138	Phase 1	Terminated	Ajai Chari

FDA Drug Approvals

Approved Product	Manufacturer	NDC Code	Route	Strength	Effective Date
No FDA approvals found for this drug.

EMA Drug Approvals

Approved Product	Authorization Holder	Status	Issued Date
No EMA approvals found for this drug.

HSA Drug Approvals

Approved Product	Manufacturer	Approval Number	Dosage Form	Strength	Approval Date
No HSA approvals found for this drug.

NMPA Drug Approvals

Approved Product	Company	Approval Number	Drug Type	Dosage Form	Approval Date
No NMPA approvals found for this drug.

PPB Drug Approvals

Approved Product	Registration No.	Company	Licence No.	Strength	Registration Date
No PPB approvals found for this drug.

TGA Drug Approvals

Approved Product	ARTG ID	Sponsor	Registration Type	Status	Registration Date
No TGA approvals found for this drug.

Health Canada Drug Approvals

Approved Product	Company	DIN	Dosage Form	Strength	Market Date
No Health Canada approvals found for this drug.

CIMA AEMPS Drug Approvals

Approved Product	Company	Registration Number	Pharmaceutical Form	Prescription Type	Status
No CIMA AEMPS (Spain) approvals found for this drug.

Philippines FDA Drug Approvals

Approved Product	Company	License Number	Dosage Form	Strength	Approval Date
No Philippines FDA approvals found for this drug.

Saudi SFDA Drug Approvals

Approved Product	Company	License Number	Dosage Form	Strength	Approval Date
No Saudi SFDA approvals found for this drug.

Malaysia NPRA Drug Approvals

Approved Product	Company	Registration Number	Dosage Form	Strength	Approval Date
No Malaysia NPRA approvals found for this drug.

UK EMC Drug Information

Medicine Name	MA Holder	MA Number	Pharmaceutical Form	Active Ingredient	Authorization Date
No UK EMC drug information found for this drug.

Related News

FDA Grants First Accelerated Approval for H3 K27M-Mutated Diffuse Midline Glioma with Dordaviprone

2 months ago

The FDA has granted accelerated approval to dordaviprone (Modeyso) for adult and pediatric patients aged 1 year and older with H3 K27M-mutated diffuse midline glioma following disease progression after prior therapy.

Jazz Pharmaceuticals Names Renee Gala as CEO in Strategic Leadership Transition

2 months ago

Jazz Pharmaceuticals' Board of Directors unanimously selected Renee Gala as President and CEO, effective August 11, 2025, succeeding co-founder Bruce Cozadd who will remain as Board Chairperson.

Jazz Pharmaceuticals Reports Strong Q1 2025 Performance with $898 Million in Revenue, Advances Pipeline with Zepzelca sNDA Submission

5 months ago

• Jazz Pharmaceuticals reported total revenues of $898 million in Q1 2025, with Xywav and Epidiolex showing strong year-over-year growth of 9% and 10% respectively. • The company submitted a supplemental New Drug Application for Zepzelca in combination with atezolizumab as maintenance therapy for first-line extensive-stage small cell lung cancer, based on promising Phase 3 trial results. • Jazz completed the acquisition of Chimerix, adding dordaviprone to its late-stage pipeline for H3 K27M-mutant diffuse glioma, with an FDA PDUFA target date of August 18, 2025.

Jazz Pharmaceuticals to Acquire Chimerix for $935M, Gaining Novel Brain Tumor Drug Candidate

7 months ago

Jazz Pharmaceuticals announces acquisition of Chimerix for $935 million, gaining dordaviprone, a first-in-class treatment for rare H3 K27M-mutant diffuse glioma with FDA Priority Review status.

Q32 Bio's Bempikibart Shows Mixed Results, BioAge's Azelaprag Faces Safety Concerns, Stocks React

9 months ago

• Q32 Bio's bempikibart showed promise in Phase IIa trial for alopecia areata (AA), achieving a 16% mean reduction in SALT score at week 24 compared to placebo. • However, bempikibart failed its Phase IIa trial for atopic dermatitis (AD), with placebo showing slightly better improvement in EASI scores, leading to investor selloff. • BioAge Labs halted its Phase II STRIDES trial of azelaprag due to liver transaminitis, causing stock downgrade and concerns about the drug's safety profile at higher doses. • Candel Therapeutics and uniQure saw stock surges following positive trial results and FDA agreement, respectively, while CervoMed and Chimerix also experienced significant stock movements.

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