FDA Accepts BLA for Denileukin Diftitox in Cutaneous Persistent/Recurrent T-Cell Lymphoma


The FDA’s acceptance of the biologics license application for denileukin diftitox for the treatment of patients with cutaneous persistent or recurrent T-cell lymphoma was supported by data from a pivotal phase 3 trial.

The FDA accepted a biologics license application (BLA) for the engineered interleukin-2 (IL-2)-diphtheria toxin fusion protein denileukin diftitox (I/ONTAK; E7777) to treat patients with cutaneous persistent or recurrent T-cell lymphoma, according to a press release from Citius Pharmaceuticals.1

The BLA for denileukin diftitox in this patient population was originally submitted in October 2022. The Prescription Drug User Fee Act (PDUFA) target action date for this agent is September 28, 2023.

The FDA’s acceptance of this BLA was based on data from a multi-center, open-label, single-arm phase 3 trial (NCT01871727). Results from the trial indicated that denileukin diftitox yielded an independent review committee (IRC)-assessed 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%) among patients with persistent or recurrent T-cell lymphoma.2

Additionally, the agent produced a clinical benefit rate of 49.3% (n = 34/69; 95% CI, 37.0%-61.6%) and a median duration of response of 6.5 months (range, 3.0-23.5) as determined by IRC, and the median time to response among patients was 1.41 months.

“The acceptance of the previously announced BLA submission for [denileukin diftitox] is another important regulatory milestone for our oncology program,” Leonard Mazur, co-founder, chairman, and CEO of Citius, said in the press release.

Denileukin diftitox is a fusion protein that combines the IL-2 receptor binding domain with diphtheria toxin fragments, causing these toxin fragments that have entered cells to inhibit protein synthesis. Denileukin diftitox is a reformulation of a previously FDA-approved treatment that was voluntarily withdrawn from the market, maintaining the same amino acid sequence of the previous agent while aiming to improve purity and bioactivity.


  1. Citius Pharmaceuticals, Inc. announces U.S. Food and Drug Administration acceptance of biologics license application of denileukin diftitox for the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma. News release. Citius Pharmaceuticals, Inc. December 1, 2022. Accessed December 2, 2022. bit.ly/3Upq3jd
  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 December 2, 2022. https://prn.to/3CaaHrV

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