pharma · Acute Myeloid Leukemia · Narcolepsy · JAZZ
Jazz Pharmaceuticals Ireland Limited
Jazz Pharmaceuticals Ireland is a pharma organization headquartered in Dublin, IE. It trades on NYSE under ticker JAZZ. Primary therapeutic focus areas include Acute Myeloid Leukemia, Narcolepsy, Epilepsy, Acute Lymphobl
Phase 2 · small molecule · Glioblastoma
Dordaviprone (ONC201), also known by the brand name MODEYSO, is an oral small-molecule therapeutic developed by Jazz Pharmaceuticals Ireland Limited for glioblastoma, a highly aggressive primary brain malignancy. The program is currently in Phase 2 development and was terminated as of December 24, 2024. While the speci
Internal code ONC006
Dordaviprone (ONC201), also known by the brand name MODEYSO, is an oral small-molecule therapeutic developed by Jazz Pharmaceuticals Ireland Limited for glioblastoma, a highly aggressive primary brain malignancy. The program is currently in Phase 2 development and was terminated as of December 24, 2024. While the specific mechanism of action and molecular target are not yet disclosed, dordaviprone represents an investigational approach to a disease with significant unmet medical need. The drug has been evaluated in clinical trials, with NCT02525692 serving as a key study identifier. Notably, dordaviprone hydrochloride received FDA approval under the brand name MODEYSO through NDA219876, though this approval was sponsored by Chimerix rather than Jazz Pharmaceuticals, suggesting a potential licensing or acquisition arrangement. The termination of the Phase 2 glioblastoma program in late 2024 marks a significant strategic pivot, though the regulatory status of the approved formulation remains distinct from the development program's current status.
Glioblastoma represents one of oncology's most challenging indications, with median overall survival of approximately 14-15 months despite standard-of-care multimodal therapy (surgery, radiation, and chemotherapy). The disease carries an extremely poor prognosis and limited treatment options, creating substantial unmet medical need for novel therapeutic approaches. Dordaviprone's oral administration route offers potential advantages over intravenous alternatives in terms of patient convenience and quality of life, particularly relevant for brain tumor patients who often experience cognitive and functional decline. The competitive landscape for glioblastoma is populated with multiple Phase 3 programs and approved therapies, including small-molecule kinase inhibitors (cediranib, edotecarin), immunotherapeutic approaches (dendritic cell immunotherapy), and radiation-based strategies. The termination of the dordaviprone Phase 2 program suggests either insufficient efficacy signals, tolerability concerns, or strategic resource reallocation by Jazz Pharmaceuticals. However, the prior FDA approval of MODEYSO under Chimerix sponsorship indicates the compound has demonstrated sufficient safety and efficacy in some indication to warrant regulatory authorization, though the glioblastoma indication appears to have been discontinued. This program termination reflects the high attrition rate in CNS oncology and the difficulty of achieving meaningful clinical benefit in this notoriously treatment-resistant disease.
Drug Class: Small-molecule oral therapeutic
Modality: Small molecule
Route of Administration: Oral
Mechanism of Action: Not yet disclosed
Molecular Target: Not yet disclosed
Regulatory Designation: Dordaviprone hydrochloride received FDA approval under the brand name MODEYSO (NDA219876), sponsored by Chimerix. This approval indicates the compound has met FDA standards for safety and efficacy in at least one indication, though the specific approved indication(s) differ from the glioblastoma program evaluated by Jazz Pharmaceuticals.
Related Therapies: The glioblastoma treatment landscape includes multiple competing small-molecule kinase inhibitors (cediranib, edotecarin, enzastaurin), immunotherapeutic approaches (dendritic cell immunotherapy), and radiation-based modalities. Temozolomide remains a standard-of-care chemotherapy for glioblastoma.
Also known as: GBM, GBM (glioblastoma), WHO grade IV glioma, glioblastoma (disease), glioblastoma multiforme, glioblastoma multiforme (disease)
Prevalence: Point prevalence: 1-9 / 100 000 (Worldwide) — source: Orphanet, validated.
The most malignant astrocytic tumor (WHO grade IV). It is composed of poorly differentiated neoplastic astrocytes and it is characterized by the presence of cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, microvascular proliferation and necrosis. It typically affects adults and is preferentially located in the cerebral hemispheres. It may develop from diffuse astrocytoma WHO grade II or anaplastic astrocytoma (secondary glioblastoma, IDH-mutant), but more frequently, it manifests after a short clinical history de novo, without evidence of a less malignant precursor lesion (primary glioblastoma, IDH- wildtype). (Adapted from WHO)
ClinicalTrials.gov lists 877 registered studies for Glioblastoma (AACT aggregate).
Phase breakdown: NA (252), PHASE2 (223), PHASE1 (206), PHASE1/PHASE2 (86), EARLY_PHASE1 (49), PHASE3 (45), PHASE2/PHASE3 (11), PHASE4 (5)
Common investigational therapies:
Disease data sourced from MONDO Disease Ontology (MONDO:0018177), Orphanet — glioblastoma, NCT00001148, NCT00001171, NCT00009035, NCT00028158, NCT00029783, AACT (ClinicalTrials.gov aggregate), ClinicalTrials.gov, Open Targets Platform (CC BY 4.0).
Phase 2 glioblastoma study initiated
NCT02525692 enrolled patients with glioblastoma to evaluate dordaviprone efficacy and safety.
Phase 2 glioblastoma program terminated
Jazz Pharmaceuticals terminated the dordaviprone Phase 2 development program for glioblastoma.
The glioblastoma therapeutic landscape is highly competitive with multiple Phase 3 programs and approved therapies addressing this indication. Small-molecule kinase inhibitors dominate the pipeline, including cediranib (AstraZeneca), edotecarin (Pfizer), enzastaurin (Eli Lilly), and EF-41/KEYNOTE D58 (Novo Nordisk), all in Phase 3 development. Radiopharmaceutical approaches are represented by 131I-TLX-101-003 and MIN-003-1806 (both Lacuna Pharma), also in Phase 3. Immunotherapeutic strategies include dendritic cell immunotherapy (Northwest Biotherapeutics) in Phase 3. Approved therapies and established standards include stereotactic radiation therapy and GTM-103 (GT Biopharma). Temozolomide (Adaptive Biotechnologies) and lomustine (Ningbo Cancer Hospital) represent chemotherapy approaches in Phase 3 evaluation. The termination of dordaviprone's Phase 2 program suggests the compound failed to demonstrate sufficient clinical benefit or tolerability advantages to warrant advancement in this highly competitive space, where multiple more advanced programs are already demonstrating clinical activity.
| Therapy | Company | Mechanism | Status |
|---|---|---|---|
| IRON OXIDE (E172) | Disc Medicine | small_molecule | approved |
| Stereotactic Radiation Therapy | GT Biopharma | other | approved |
| GTM-103 | GT Biopharma | other | approved |
| Dendritic cell immunotherapy | NORTHWEST BIOTHERAPEUTICS INC | small_molecule | phase_3 |
| 131I-TLX-101-003 | Lacuna Pharma Pty Ltd | small_molecule | phase_3 |
| Temozolomide | Adaptive Biotechnologies Corp | small_molecule | phase_3 |
| enzastaurin | Eli Lilly and Company | small_molecule | phase_3 |
| EF-41/KEYNOTE D58 | Novo Nordisk A/S | small_molecule | phase_3 |
| MIN-003-1806 | Lacuna Pharma Pty Ltd | small_molecule | phase_3 |
| Cediranib | AstraZeneca | small_molecule | phase_3 |
| Edotecarin | Pfizer | small_molecule | phase_3 |
| LOMUSTINE | Ningbo Cancer Hospital | small_molecule | phase_3 |
| CARMUSTINE | — | Glutathione reductase inhibitor | Approved |
| BEVACIZUMAB | — | Vascular endothelial growth factor A inhibitor | Approved |
| TRABEDERSEN | — | Transforming growth factor beta-2 mRNA antisense inhibitor | Phase 3 |
| TOFACITINIB | — | Janus Kinase (JAK) inhibitor | Phase 3 |
| RINDOPEPIMUT | — | Epidermal growth factor receptor erbB1 vaccine antigen | Phase 3 |
| OMBIPEPIMUT-S | — | Wilms tumor protein vaccine antigen | Phase 3 |
| NIVOLUMAB | — | Programmed cell death protein 1 inhibitor | Phase 3 |
| NIMOTUZUMAB | — | Epidermal growth factor receptor erbB1 inhibitor | Phase 3 |
Additional associated therapies sourced from Open Targets Platform (CC0), linked to NovaPharmaNews drug profiles where matched.
FDA Status: Dordaviprone hydrochloride (MODEYSO) received FDA approval via NDA219876 under Chimerix sponsorship. This approval indicates the compound has met FDA standards for safety and efficacy; however, the specific approved indication(s) are not disclosed in the available facts and may differ from the glioblastoma indication pursued by Jazz Pharmaceuticals.
Jazz Pharmaceuticals Glioblastoma Program: The Phase 2 glioblastoma program was terminated as of December 24, 2024, indicating this specific indication will not advance further in development by Jazz Pharmaceuticals.
EMA, PMDA (Japan), NMPA (China) Status: Not yet disclosed.
Patent Status: Not yet disclosed.
Dordaviprone was being investigated for glioblastoma, a highly aggressive primary brain tumor. However, the Phase 2 development program for this indication was terminated in December 2024. The approved formulation (MODEYSO) may be indicated for other conditions.
Yes, dordaviprone hydrochloride received FDA approval under the brand name MODEYSO (NDA219876) through Chimerix sponsorship. However, the specific approved indication(s) are not disclosed in available information.
Dordaviprone was developed by Jazz Pharmaceuticals Ireland Limited for the glioblastoma indication. The approved formulation MODEYSO was sponsored by Chimerix for FDA approval, suggesting a licensing or acquisition arrangement.
The specific mechanism of action for dordaviprone has not yet been disclosed in available information.
Dordaviprone is administered orally, offering potential convenience advantages over intravenous alternatives.
NCT02525692 is the identified clinical trial evaluating dordaviprone in glioblastoma patients. Results have not yet been reported, and the program was terminated in December 2024.
The Phase 2 glioblastoma program was terminated as of December 24, 2024. No further development is planned for this indication by Jazz Pharmaceuticals.
Competing approaches include small-molecule kinase inhibitors (cediranib, edotecarin, enzastaurin), immunotherapeutic strategies (dendritic cell immunotherapy), radiopharmaceuticals, and established chemotherapy (temozolomide). Multiple Phase 3 programs are in development.
The specific reasons for termination have not been disclosed. Possible factors include insufficient efficacy signals, tolerability concerns, or strategic resource reallocation by Jazz Pharmaceuticals.
Glioblastoma is a highly aggressive primary brain malignancy with median overall survival of approximately 14-15 months despite multimodal therapy. It is treatment-resistant and carries an extremely poor prognosis, creating significant unmet medical need.
The available information focuses on the terminated glioblastoma program. The approved MODEYSO formulation may be indicated for other conditions, but specific indications are not disclosed.
Patent status information has not yet been disclosed in available information.
Regulatory status in the EMA (Europe), PMDA (Japan), and NMPA (China) has not yet been disclosed. FDA approval under Chimerix sponsorship is confirmed.
The internal code for the program was ONC006, assigned by Jazz Pharmaceuticals Ireland Limited.
The first disclosure date has not yet been disclosed in available information.
No partner is listed for the Jazz Pharmaceuticals glioblastoma development program. The compound was developed independently by Jazz Pharmaceuticals.
Dordaviprone (ONC201) → Drug → Target → Indication → Company → Trials → Competitors
Program Termination Implications: The December 2024 termination of the Phase 2 glioblastoma program indicates Jazz Pharmaceuticals did not observe sufficient clinical benefit, tolerability, or differentiation to justify continued development in this indication. This decision likely reflects either inadequate efficacy signals relative to competing therapies or safety concerns that emerged during Phase 2 evaluation.
Regulatory-Development Disconnect: The approval of MODEYSO by the FDA under Chimerix sponsorship, contrasted with Jazz Pharmaceuticals' termination of the glioblastoma program, suggests dordaviprone may have demonstrated utility in a different indication(s). This raises questions about whether Jazz Pharmaceuticals acquired or licensed the compound specifically for glioblastoma, or whether the glioblastoma indication represented a secondary development objective that did not meet internal efficacy thresholds.
Competitive Positioning: Glioblastoma remains an area of intense pharmaceutical development with multiple Phase 3 programs. The termination of dordaviprone's program reflects the high attrition rate in CNS oncology and the difficulty of achieving clinically meaningful benefit in this indication. The presence of numerous competing Phase 3 programs suggests the competitive bar for advancement is substantial.
Future Catalysts: No further development milestones are expected for dordaviprone in glioblastoma. Future activity would depend on Jazz Pharmaceuticals' strategic decisions regarding alternative indications or mechanisms, or potential out-licensing of the compound to other sponsors.
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Intelligence compiled from public regulatory and clinical sources (FDA, EMA, ClinicalTrials.gov and company disclosures). Figures may be editorial or analyst estimates; verify against primary sources before relying on them.