Last reviewed 2026-05-28 · How we verify

Ontak (DENILEUKIN DIFTITOX)

Ontak (generic name: DENILEUKIN DIFTITOX) is a CD25-directed Cytotoxin [EPC] Recombinant protein drug developed by Eisai. It is currently FDA-approved (first approved 1999) for Primary cutaneous T-cell lymphoma, Refractory peripheral T-cell lymphoma.

Ontak works by binding to the interleukin-2 receptor on cancer cells, triggering a toxic response that kills the cells.

Ontak, also known as denileukin diftitox, is a protein-based inhibitor that targets elongation factor 2. It is used to treat various types of cancer, including lymphoma, fallopian tube cancer, ovarian clear cell cystadenocarcinoma, ovarian endometrioid adenocarcinoma, and ovarian mixed epithelial carcinoma.

At a glance

Mechanism of action

Imagine your immune system has a special key that unlocks a receptor on cancer cells. Ontak is like a fake key that looks just like the real one, so it can bind to the receptor and trigger a toxic response that kills the cancer cells. This helps to slow down the growth of the cancer.

Approved indications

• Primary cutaneous T-cell lymphoma
• Refractory peripheral T-cell lymphoma

Boxed warnings

• 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 )

Common side effects

• Increased transaminases
• Albumin decreased
• Nausea
• Edema
• Hemoglobin decreased
• Fatigue
• Musculoskeletal pain
• Rash
• Chills
• Constipation
• Pyrexia
• Capillary leak syndrome

Serious adverse events

• Capillary leak syndrome
• Infusion-related reaction
• Sepsis
• Skin infection
• Pyrexia
• Rash

Key clinical trials

• A Study to Investigate the Safety and Efficacy of IOV-3001 in Adults With Advanced Melanoma Who Will Receive Lifileucel (PHASE1,PHASE2)
• HCW9302 (Interleukin-2 Fusion Protein) for Alopecia Areata (PHASE1)
• T-regulatory Cell Depletion with E7777 Combined with Pembrolizumab in Recurrent or Metastatic Solid Tumors (PHASE1,PHASE2)
• A Study of Remitoro in Participants With Recurrent or Refractory Peripheral T Cell Lymphoma and Cutaneous T Cell Lymphoma (All Case Study)
• Denileukin Diftitox in Treating Patients With Non-Hodgkin's Lymphoma (PHASE2)
• Therapeutic Autologous Lymphocytes, Aldesleukin, and Denileukin Diftitox in Treating Patients With Stage III-IV Melanoma (PHASE1,PHASE2)
• Study of Denileukin Diftitox in Participants With Stage IIIC and Stage IV Melanoma (PHASE2)
• Treatment for Acute Graft-Versus-Host Disease (BMT CTN 0302) (PHASE2)

Primary sources

Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.

Competitive intelligence

For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:

• Ontak CI brief — competitive landscape report
• Ontak updates RSS · CI watch RSS
• Eisai portfolio CI

Frequently asked questions about Ontak

Related

• Drug class: All CD25-directed Cytotoxin [EPC] drugs
• Target: All drugs targeting Interleukin-2 receptor
• Manufacturer: Eisai — full pipeline
• Therapeutic area: All drugs in Oncology
• Indication: Drugs for Primary cutaneous T-cell lymphoma
• Indication: Drugs for Refractory peripheral T-cell lymphoma

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing