BLA Submitted to the FDA for Denileukin Diftitox in Cutaneous Persistent/Recurrent T-Cell Lymphoma


Data from a pivotal phase 3 trial support a recent biologics license application for denileukin diftitox that was submitted to the FDA.

A biologics license application (BLA) was submitted to the FDA for the engineered IL-2 diphtheria toxin fusion protein denileukin diftitox (Ontak) as a potential treatment for patients with persistent or recurrent cutaneous T-cell lymphoma (CTCL), according to a press release from Citius Pharmaceuticals.1

The application was bolstered by positive topline results from a single-arm phase 3 clinical trial (NCT01871727) assessing denileukin diftitox. An independent review committee (IRC) identified an objective response rate (ORR) of 36.2% (n = 25/69; 95% CI, 25.0%-48.7%) and an investigator-assessed ORR of 42.3% (95% CI, 30.6%-54.6%).2 The clinical benefit rate was 49.3% (n = 34/69; 95% CI, 37.0%-61.6%) by IRC. Moreover, the median duration of response was 6.5 months (range, 3.0+ to 23.5+) by IRC and the median time to response was 1.41 months.2

“Citius is proud to advance the only potential CTCL therapeutic with a mechanism of action that delivers a cytotoxic protein by binding to the IL-2 receptors found in malignant T-cells and immunosuppressive T-regulatory cells. We look forward to continuing to engage with the FDA as they review our BLA and bringing this treatment option to patients, if approved,” Leonard Mazur, chairman and chief executive officer at Citius Pharmaceuticals, said in the press release. "The BLA filing for denileukin diftitox marks the first of our pipeline candidates to be submitted for FDA approval.”

Denileukin diftitox is a recombinant fusion protein that binds to IL-2 receptors on the cell surface and causes diphtheria toxin fragments inside the cells to inhibit protein synthesis. The agent is a reformulation of an FDA-approved predecessor marketed in the United States from 1999 to 2014 before a voluntary withdrawal from the market. This new formulation is more bioactive relative to its predecessor, having already been approved in Japan in 2021.

The multicenter, open-label study included 69 patients in the IRC primary efficacy analysis and 71 in the investigator efficacy analysis who received intravenous denileukin diftitox at 9 μ/kg for 5 consecutive days every 21-day cycle. The dosage was determined during the lead-in portion of the trial, and the data were assessed after up to 30 months of follow-up.

To be included, the study required patients to have histopathologically diagnosed CTCL confirmed by skin biopsy, lymph node assessment, or blood assessment. Patients also needed to have detectable CD25 on at least 20% of the total lymphoid infiltrate in biopsied lesions by immunohistochemistry testing. Other inclusion criteria were an ECOG performance status of 0 or 1 and a life expectancy of at least 12 months.

Exclusion criteria included prior therapy with the study agent, serious intercurrent illness, and any active malignancies in the previous 24 months aside from CTCL, definitively treated basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix.


  1. Citius Pharmaceuticals, Inc. submits biologics license application to the U.S. Food and Drug Administration for denileukin diftitox for the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma. News Release. Citius Pharmaceuticals. September 28, 2022. Accessed October 5, 2022.
  2. Citius Pharmaceuticals reports topline data from the pivotal phase 3 study of cancer immunotherapy I/ONTAK (E7777) for the treatment of persistent or recurrent cutaneous t-cell lymphoma (CTCL) in support of BLA submission. News Release. Citius Pharmaceuticals. April 6, 2022. Accessed October 5, 2022.
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