{"entity":{"id":"denileukin-diftitox","kind":"drug","name":"Denileukin diftitox","aka":["Ontak (1999 to 2014)","E7777"],"tldr":"Denileukin diftitox (Lymphir) is an infusion that uses the interleukin-2 signal as a homing device to deliver a bacterial toxin into cutaneous T-cell lymphoma cells. It was withdrawn in 2014 and returned in an improved form in 2024.","summary":"The original denileukin diftitox (Ontak) was approved in 1999 for persistent or recurrent CD25-positive cutaneous T-cell lymphoma and withdrawn from the US market in 2014 because of manufacturing problems. A reformulated, higher-purity product was approved by the FDA in August 2024 as Lymphir for adults with relapsed or refractory stage I to III CTCL after at least one systemic therapy, on Study 302, an open-label single-arm trial in which 36% of patients responded (with CD25 expression on at least 20% of malignant cells required for entry). Capillary leak syndrome, infusion reactions and visual changes carry boxed warnings and require premedication and close monitoring.","status":"approved","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Denileukin_diftitox","links":[{"label":"US label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=denileukin%20diftitox"},{"label":"NCI drug page","url":"https://www.cancer.gov/about-cancer/treatment/drugs/denileukindiftitox-cxdl"}],"tags":["nci-list"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":["cd25"],"drugs":[],"companies":["citius-pharmaceuticals","eisai"],"institutions":[],"pathways":[],"terms":[],"trials":["nct01127451","nct00299689","nct00880360"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Cutaneous T-cell lymphoma has no cancer record yet."],"brand":"Lymphir","modality":"IL-2 receptor-directed cytotoxin (fusion protein)","mechanism":"Fusion of interleukin-2 with diphtheria toxin fragments A and B; binds CD25-expressing cells, is internalised, and the toxin blocks protein synthesis and kills the cell.","approvals":[{"region":"US","year":1999,"indication":"Persistent or recurrent CD25-positive CTCL (Ontak; withdrawn 2014)"},{"region":"US","year":2024,"indication":"Relapsed or refractory stage I to III CTCL after at least one systemic therapy (Lymphir)"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[{"date":"1999-02-05","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint, with a confirmatory trial required.","indication":"Persistent or recurrent cutaneous T-cell lymphoma expressing the CD25 component of IL-2 receptor"},{"date":"2008-10-15","type":"conversion","region":"US","note":"Confirmed: the accelerated approval of 1999 converted to traditional approval 9.7 years after it was granted.","indication":"Persistent or recurrent cutaneous T-cell lymphoma expressing the CD25 component of IL-2 receptor"}]},"route":"/drugs/denileukin-diftitox/","neighbours":{"target":[{"id":"cd25","kind":"target","name":"CD25 (IL-2 receptor alpha)","route":"/targets/cd25/"}],"company":[{"id":"citius-pharmaceuticals","kind":"company","name":"Citius Pharmaceuticals","route":"/companies/citius-pharmaceuticals/"},{"id":"eisai","kind":"company","name":"Eisai","route":"/companies/eisai/"}],"trial":[{"id":"nct00880360","kind":"trial","name":"A Trial of Intravenous Denileukin Diftitox in Stage III or IV Ovarian Cancer","route":"/trials/nct00880360/"},{"id":"nct00299689","kind":"trial","name":"Phase II Trial of Ontak With Metastatic Melanoma","route":"/trials/nct00299689/"},{"id":"nct01127451","kind":"trial","name":"Study of Denileukin Diftitox in Participants With Stage IIIC and Stage IV Melanoma","route":"/trials/nct01127451/"}],"cancer":[{"id":"mycosis-fungoides","kind":"cancer","name":"Mycosis fungoides","route":"/cancers/mycosis-fungoides/"}]}}