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 · DLBCL
Defibrotide sodium (DEFITELIO) is an intravenous small-molecule therapeutic developed by Jazz Pharmaceuticals Ireland Limited for diffuse large B-cell lymphoma (DLBCL), a common and aggressive form of non-Hodgkin lymphoma. The program, designated JZP395-201, is a Phase 2 trial that was terminated as of December 9, 2021
Internal code JZP395-201
Defibrotide sodium (DEFITELIO) is an intravenous small-molecule therapeutic developed by Jazz Pharmaceuticals Ireland Limited for diffuse large B-cell lymphoma (DLBCL), a common and aggressive form of non-Hodgkin lymphoma. The program, designated JZP395-201, is a Phase 2 trial that was terminated as of December 9, 2021. DEFITELIO is already approved in the United States under NDA208114, where it is marketed by Jazz Pharmaceuticals Inc; however, this approval was originally granted for a different indication (hepatic veno-occlusive disease prophylaxis in hematopoietic stem cell transplantation). The DLBCL program represents an investigational expansion of the approved drug into oncology. The mechanism of action and specific target for the DLBCL indication are not yet disclosed. The termination of the Phase 2 trial in December 2021 marks the end of active development in this indication, with no further milestones currently projected.
Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma, affecting tens of thousands of patients annually in developed markets. While standard-of-care regimens (rituximab-based chemotherapy combinations) achieve remission in approximately 60% of patients, relapsed and refractory DLBCL remains a significant unmet medical need with poor prognosis and limited treatment options. The competitive landscape for DLBCL is intensifying, with multiple Phase 3 programs from major pharmaceutical companies (Roche, AbbVie, Regeneron, Merck, Incyte) evaluating novel bispecific antibodies, antibody-drug conjugates, and combination regimens. The termination of the defibrotide DLBCL program suggests the compound did not demonstrate sufficient clinical benefit or differentiation to justify continued development in this highly competitive space. The decision underscores the challenge of repurposing non-oncology drugs into solid competitive oncology indications without clear mechanistic rationale or superior efficacy signals.
Drug Class: Polydeoxyribonucleotide (PDRN) derivative; small-molecule intravenous therapeutic.
Modality: Small molecule.
Route of Administration: Intravenous infusion.
Mechanism of Action: Not yet disclosed for the DLBCL indication.
Target: Not yet disclosed for the DLBCL indication.
Approved Formulation: DEFITELIO (defibrotide sodium) is approved in the United States (NDA208114) as a prophylactic agent for hepatic veno-occlusive disease in patients undergoing hematopoietic stem cell transplantation. The DLBCL program represents an investigational oncology expansion.
Related Therapies: In DLBCL, defibrotide competes against established chemotherapy regimens (R-CHOP, R-EPOCH) and emerging targeted agents including bispecific antibodies (epcoritamab, odronextamab), antibody-drug conjugates (polivy, minjuvi), and immunomodulatory agents (lenalidomide-based combinations).
Also known as: DLBCL
Prevalence: Point prevalence: 1-5 / 10 000 (Europe) — source: Orphanet, validated.
Diffuse large B-cell lymphoma is the most common subtype of non-Hodgkin lymphoma (NHL) in adults characterized by a median age of presentation in the sixth decade of life (but also rarely occurring in adolescents and children) with the initial presentation being single or multiple rapidly growing masses (that may or may not be painful) in nodal or extranodal sites (such as thyroid, skin, breast, gastrointestinal tract, testes, bone, or brain) and that can be accompanied by symptoms of fever, night sweats and weight loss. DLBCL has an aggressive disease course, with the elderly having a poorer prognosis than younger patients, and with relapses being common.
ClinicalTrials.gov lists 606 registered studies for Diffuse, Large B-Cell, Lymphoma (AACT aggregate).
Phase breakdown: PHASE2 (204), NA (126), PHASE1 (109), PHASE1/PHASE2 (78), PHASE3 (63), EARLY_PHASE1 (9), PHASE2/PHASE3 (9), PHASE4 (8)
Common investigational therapies:
Disease data sourced from MONDO Disease Ontology (MONDO:0018905), Orphanet — diffuse large B-cell lymphoma, NCT00022971, NCT00075478, NCT00333008, NCT00355199, NCT00386321, AACT (ClinicalTrials.gov aggregate), ClinicalTrials.gov, Open Targets Platform (CC BY 4.0).
Program Terminated
Phase 2 trial JZP395-201 (NCT03954106) in DLBCL was terminated; no further development milestones disclosed.
The DLBCL therapeutic landscape is dominated by Phase 3 programs from major oncology players. Roche is advancing polivy (polatuzumab vedotin) in combination with rituximab and chemotherapy, alongside MabThera (rituximab) backbone regimens. AbbVie is evaluating epcoritamab (GEN3013), a bispecific anti-CD3/anti-CD20 antibody, in multiple Phase 3 settings. Regeneron is developing odronextamab, another bispecific antibody targeting CD20 and CD3. Merck is studying zilovertamab vedotin, an antibody-drug conjugate. Incyte is progressing minjuvi (tafasitamab) and Zelvina (selinexor) combinations. Karyopharm is conducting Phase 2/3 trials of selinexor (KPT-330) in relapsed/refractory DLBCL. Genmab is advancing GEN3014 DP with DARZALEX (daratumumab). The termination of defibrotide's DLBCL program reflects the difficulty of competing in this crowded space without a clearly differentiated mechanism or compelling early efficacy data. Most competing programs employ bispecific antibodies or antibody-drug conjugates with established immunological rationale in B-cell lymphomas, whereas defibrotide's mechanism in DLBCL was not disclosed, suggesting limited translational evidence.
| Therapy | Company | Mechanism | Status |
|---|---|---|---|
| Gemcitabine 38 mg/ml Concentrate for Solution for Infusion, Revlimid 25 mg hard capsules, Epcoritamab (GEN3013), Epcoritamab (GEN3013), Oxaliplatin 5mg/ml Concentrate for Solution for Infusion, Revlimid 5 mg hard capsules, Gemcitabine 38 mg/ml Concentrate for Solution for Infusion, Truxima 500 mg concentrate for solution for infusion, Revlimid 20 mg hard capsules, Truxima 100 mg concentrate for solution for infusion | AbbVie Deutschland GmbH & Co. KG | small_molecule | phase_3 |
| MabThera 500 mg concentrate for solution for infusion, Polivy 140 mg powder for concentrate for solution for infusion., GEMCITABINE , OXALIPLATIN | Hoffmann-La Roche | small_molecule | phase_3 |
| Odronextamab | Regeneron UK Limited | small_molecule | phase_3 |
| Vincristine placebo, VINCRISTINE , Polivy 140 mg powder for concentrate for solution for infusion., MabThera 500 mg concentrate for solution for infusion | Hoffmann-La Roche | small_molecule | phase_3 |
| RITUXIMAB , SODIUM CHLORIDE, Placebo for lenalidomide 25mg, PREDNISONE , MINJUVI 200 mg powder for concentrate for solution for infusion, PREDNISOLONE , LENALIDOMIDE, DOXORUBICIN , Placebo for lenalidomide 10mg, VINCRISTINE , LENALIDOMIDE, Placebo for lenalidomide 15mg, LENALIDOMIDE, CYCLOPHOSPHAMIDE | Incyte | small_molecule | phase_3 |
| Truxima 500 mg concentrate for solution for infusion, Cyclophosphamide Injection 500 mg., Epcoritamab (GEN3013), Vincristine Sulfate 1 mg/ml solution for injection, Doxorubicinhydrochlorid Bendalis 2 mg/ml Injektionslösung, Epcoritamab (GEN3013), Truxima 100 mg concentrate for solution for infusion, Prednisone Zentiva 5 mg compresse | AbbVie Deutschland GmbH & Co. KG | small_molecule | phase_3 |
| CYCLOPHOSPHAMIDE , -, PREDNISONE , PREDNISOLONE , VINCRISTINE, DOXORUBICIN , RITUXIMAB , Zilovertamab vedotin | Merck Sharp and Dohme | small_molecule | phase_3 |
| Zelvina 25 mg hard capsules, Zelvina 10 mg hard capsules, Zelvina 15 mg hard capsules, Zelvina 5 mg hard capsules, Zelvina 20 mg hard capsules, MINJUVI 200 mg powder for concentrate for solution for infusion | Incyte | small_molecule | phase_3 |
| COLECALCIFEROL , PREDNISONE | Fondazione Telethon ETS | small_molecule | phase_3 |
| Ondansetron Aurobindo 8 mg Filmtabletten, Zarzio 48 MU/0.5 ml solution for injection or infusion in pre-filled syringe, Rixathon 500 mg concentrate for solution for infusion, Zarzio 48 MU/0.5 ml solution for injection or infusion in pre-filled syringe, Rixathon 500 mg concentrate for solution for infusion, Cisplatin 1 mg/ml Concentrate for Solution for Infusion, Dexametazona Krka 4 mg comprimate, EMEND 125 mg+80 mg hard capsules, Carboplatin Hikma 10 mg/ml Konzentrat zur Herstellung einer Infusionslösung, G | Karyopharm Therapeutics Inc | small_molecule | phase_3 |
| GEN3014 DP, DARZALEX 1800 mg solution for injection | Genmab A/S | small_molecule | phase_2 |
| A Phase 2b Open-label Study of Selinexor (KPT-330) in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) | Karyopharm Therapeutics Inc | other | phase_2 |
| TISAGENLECLEUCEL | — | B-lymphocyte antigen CD19 binding agent | Approved |
| TAFASITAMAB | — | B-lymphocyte antigen CD19 binding agent | Approved |
| SELINEXOR | — | Exportin-1 inhibitor | Approved |
| POLATUZUMAB VEDOTIN | — | B-cell antigen receptor complex-associated protein beta chain binding agent | Approved |
| LONCASTUXIMAB TESIRINE | — | B-lymphocyte antigen CD19 binding agent | Approved |
| GLOFITAMAB | — | B-lymphocyte antigen CD20 binding agent | Approved |
| EPCORITAMAB | — | B-lymphocyte antigen CD20 binding agent | Approved |
| CRIZOTINIB | — | Hepatocyte growth factor receptor inhibitor | Approved |
Additional associated therapies sourced from Open Targets Platform (CC0), linked to NovaPharmaNews drug profiles where matched.
United States (FDA): Defibrotide sodium (DEFITELIO) is approved under NDA208114 for the prophylaxis of hepatic veno-occlusive disease in patients undergoing hematopoietic stem cell transplantation. The DLBCL indication (Phase 2 trial JZP395-201) has not been approved and development was terminated in December 2021.
European Union (EMA): Regulatory status for DLBCL indication not yet disclosed.
Japan (PMDA): Regulatory status for DLBCL indication not yet disclosed.
China (NMPA): Regulatory status for DLBCL indication not yet disclosed.
The termination of the Phase 2 trial precludes progression to regulatory filing for the DLBCL indication.
DEFITELIO is approved in the United States for the prophylaxis of hepatic veno-occlusive disease in patients undergoing hematopoietic stem cell transplantation. The Phase 2 program JZP395-201 investigated its use in diffuse large B-cell lymphoma (DLBCL), but this trial was terminated in December 2021.
No. Defibrotide is not approved for DLBCL. The Phase 2 trial (JZP395-201) in DLBCL was terminated on December 9, 2021, and no regulatory applications for this indication have been filed.
The mechanism of action of defibrotide in DLBCL has not been disclosed. This lack of transparency regarding the rationale for the DLBCL program may have contributed to the decision to terminate the trial.
Defibrotide sodium (DEFITELIO) is developed and marketed by Jazz Pharmaceuticals Inc in the United States. The DLBCL program was sponsored by Jazz Pharmaceuticals Ireland Limited.
Defibrotide is administered intravenously as an infusion.
The Phase 2 trial JZP395-201 (NCT03954106) was designed to evaluate defibrotide in DLBCL. This trial was terminated on December 9, 2021, and results have not been reported.
The specific reasons for termination have not been disclosed. Possible factors include insufficient efficacy, safety concerns, or strategic deprioritization by Jazz Pharmaceuticals.
The Phase 2 program is terminated as of December 9, 2021. No further development milestones are projected for this indication.
Competitors include epcoritamab (AbbVie), odronextamab (Regeneron), polivy (Roche), minjuvi (Incyte), zilovertamab vedotin (Merck), and selinexor (Karyopharm). Most are in Phase 3 development with bispecific antibodies or antibody-drug conjugates.
Defibrotide is classified as a small molecule. It is a polydeoxyribonucleotide (PDRN) derivative administered intravenously.
DLBCL is the most common type of non-Hodgkin lymphoma. While standard-of-care rituximab-based chemotherapy achieves remission in ~60% of patients, relapsed and refractory DLBCL has poor prognosis and limited treatment options, creating significant unmet need.
The exact approval date for DEFITELIO is not disclosed in the facts. The drug is approved under NDA208114 for hepatic veno-occlusive disease prophylaxis in hematopoietic stem cell transplantation recipients.
No partner or licensee is disclosed for the DLBCL program. The program was sponsored solely by Jazz Pharmaceuticals Ireland Limited.
The specific patient population (newly diagnosed, relapsed/refractory, treatment-naive, etc.) for the DLBCL trial is not disclosed. The trial design and eligibility criteria have not been publicly detailed.
Based on the facts provided, no other active oncology trials of defibrotide are disclosed. Development focus appears limited to the approved veno-occlusive disease indication.
Defibrotide → Drug → Target → Indication → Company → Trials → Competitors
Strategic Implications: The termination of JZP395-201 reflects Jazz Pharmaceuticals' decision to deprioritize the DLBCL indication for defibrotide. This may indicate insufficient efficacy signals, safety concerns, or strategic resource reallocation. Jazz's core oncology focus has centered on hematologic malignancies and CNS disorders; the DLBCL program may have been a lower-priority exploratory expansion of the approved veno-occlusive disease indication.
Competitive Implications: The exit removes a potential minor competitor from an already crowded DLBCL market. The Phase 3 programs from Roche, AbbVie, Regeneron, and others are advancing bispecific antibodies and antibody-drug conjugates with established mechanisms in B-cell lymphomas. Defibrotide's lack of disclosed mechanism and early termination suggest it could not compete on efficacy or differentiation.
Future Catalysts: No further development milestones are expected for defibrotide in DLBCL. Jazz may continue to explore other oncology indications or maintain focus on the approved veno-occlusive disease indication. Publication of Phase 2 data (if any) could provide retrospective insights into why the program was terminated.
Expected Milestones: None projected for the DLBCL program. Competitive Phase 3 readouts from Roche, AbbVie, and Regeneron in DLBCL are expected over the coming years and will define the standard-of-care landscape.
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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.