ONTAK (denileukin diftitox)
ONTAK is indicated for the treatment of Cutaneous T-Cell Lymphoma.
How ONTAK Works
Denileukin diftitox-cxdl is a fusion protein designed to deliver the cytocidal action of diphtheria toxin to cells expressing the IL-2 receptor. Upon cellular uptake, the diphtheria toxin fragment is cleaved and released, where it inhibits protein synthesis and leads to cell death. This mechanism allows the drug to deplete immunosuppressive regulatory T lymphocytes and exert direct antitumor activity on IL-2R-expressing tumors.
Development Insights
Details
- Status
- Prescription
- First Approved
- 1999-02-05
- Routes
- N/A
- Dosage Forms
- VIAL
ONTAK Approval History
What ONTAK Treats
1 indicationsONTAK is approved for 1 conditions since its original approval in 1999. These indications span multiple therapeutic areas including oncology, immunology, and more.
- Cutaneous T-Cell Lymphoma
ONTAK Boxed Warning
CAPILLARY LEAK SYNDROME Capillary leak syndrome (CLS), including life-threatening or fatal reactions, can occur in patients receiving LYMPHIR. Monitor patients for signs and symptoms of CLS during treatment. Withhold LYMPHIR until CLS resolves, or permanently discontinue based on severity [see Dosage and Administration ( 2.1 , 2.4 ) and Warnings and Precautions ( 5.1 )] . WARNING: CAPILLARY LEAK SYNDROME See full prescribing information for complete boxed warning. Capillary leak syndrome (CLS), ...
WARNING: CAPILLARY LEAK SYNDROME Capillary leak syndrome (CLS), including life-threatening or fatal reactions, can occur in patients receiving LYMPHIR. Monitor patients for signs and symptoms of CLS during treatment. Withhold LYMPHIR until CLS resolves, or permanently discontinue based on severity [see Dosage and Administration ( 2.1 , 2.4 ) and Warnings and Precautions ( 5.1 )] . WARNING: CAPILLARY LEAK SYNDROME See full prescribing information for complete boxed warning. Capillary leak syndrome (CLS), including life-threatening or fatal reactions, can occur in patients receiving LYMPHIR. Monitor patients for signs and symptoms of CLS during treatment. Withhold LYMPHIR until CLS resolves or permanently discontinue based on severity. ( 2.1 , 2.4 , 5.1 )
ONTAK Target & Pathway
ProTarget
ONTAK Competitive Set
ProThree rings of competition based on shared molecular targets and treated indications.
Direct competitors
Same target(s) AND same indication — head-to-head.
Indication competitors
Same indication, different mechanism — what else might this patient receive?
Filters applied: drops same-active-ingredient (505(b)(2) reformulations), route-mismatch (topical vs systemic), and cross-therapeutic-area matches in same-indication rings.
What's emerging in ONTAK's indications
See all emerging drugs →Phase 3 candidates targeting molecules with no FDA-approved drug, in indications ONTAK treats. First-in-class if their pivotal trials read out positive.
Drugs Similar to ONTAK
3 of 9FDA-approved drugs for similar conditions. Compare mechanisms and indications to understand treatment alternatives.
Clinical Trial Registry
7 trials| Trial | Sponsor ID | Phase | Status | Title |
|---|---|---|---|---|
| NCT00945269 | 2271.00 NCI-2010-00738, K12CA076930 | Ph 1, Ph 2 | terminated | Therapeutic Autologous Lymphocytes, Aldesleukin, and Denileukin Diftitox in Treating Patients With Stage III-IV Melanoma |
| NCT01127451 results posted | E7272-701 | Ph 2 | completed | Study of Denileukin Diftitox in Participants With Stage IIIC and Stage IV Melanoma |
| NCT00632827 results posted | 072518 NCI-2011-01285 | Ph 2 | terminated | Treatment of PTCL With Aggressive Induction Therapy Followed by Autologous SCT Using Denileukin Diftitox (Ontak) |
| NCT01106950 results posted | 2010LS010 MT2010-02, 1003M79954 | Ph 2 | terminated | Haploidentical Natural Killer Cells to Treat Refractory or Relapsed Acute Myelogenous Leukemia (AML) |
| NCT00460109 results posted | NCCTG-N0682 NCI-2009-00662, CDR0000539551 | Ph 2 | completed | Rituximab and Denileukin Diftitox in Treating Patients With Previously Untreated Stage III or Stage IV Follicular B-Cell Non-Hodgkin's Lymphoma |
| NCT00726037 results posted | 200732 | Ph 2 | terminated | A Pilot Study, Evaluating the Efficacy of Regulatory T-cell Suppression by Ontak in Metastatic Pancreatic Cancer |
| NCT00801918 | AAAC8963 | Ph 2 | withdrawn | Denileukine Diftitox for Relapsed ALCL |
Active Pipeline
Ongoing clinical trials by development phase
Key Completed Trials
Completed studies with published results, ranked by significance
Trial Timeline
Full development history with FDA approval milestones
Understanding FDA Approval Types
| Count | Type | What it means |
|---|---|---|
| - | ORIG | Original approval - drug first enters market |
| - | SUPPL - Efficacy | New indication (new disease/condition approved) |
| - | SUPPL - Labeling | Label text changes (warnings, dosing updates) |
| - | SUPPL - Manufacturing | Production changes (new facility) |
| - | SUPPL - Chemistry | Formulation changes (new dosage strength) |
Green lines in the timeline show ORIG and Efficacy approvals - the clinically meaningful milestones.
ONTAK FDA Label Details
Indications & Usage
FDA Label (PDF)ONTAK is indicated for the treatment of Cutaneous T-Cell Lymphoma.
WARNING: CAPILLARY LEAK SYNDROME Capillary leak syndrome (CLS), including life-threatening or fatal reactions, can occur in patients receiving LYMPHIR. Monitor patients for signs and symptoms of CLS during treatment. Withhold LYMPHIR until CLS resolves, or permanently discontinue based on severity [...
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Data Sources
Data sourced from official FDA and NIH databases. Click links to verify on original sources.
How We Calculate These Metrics
Trial Activity Stage
Measures the current development activity pattern based on trial phases, status, and trends. Important: This measures R&D activity, not commercial lifecycle.
Trial statuses: "Active" means recruiting or ongoing. "Completed" means reached planned endpoint. "Terminated" means stopped early—often due to safety, efficacy, or business reasons.
- Growth: High proportion of early-phase trials (Phase 1/2), active development
- Expansion: Significant Phase 3 activity, approaching or pursuing approvals
- Mature: Substantial Phase 4 post-marketing studies
- Stable: Mixed phase distribution, steady development
- Declining: Low active trial ratio, reduced R&D investment