FDA Considers BLA for I/ONTAK for the Treatment of Persistent or Recurrent CTCL

The FDA will conduct a regular review of the application submitted for approval of I/ONTAK in patients with persistent or recurrent cutaneous T-cell lymphoma.

The FDA has accepted the biologics license application for denileukin diftitox (I/ONTAK; E777), a potential treatment option of patients with persistent or recurrent cutaneous T-cell lymphoma (CTCL). The FDA plans to decide on the BLA by September 28, 2022.1

Results from a pivotal phase 3 E7777-G000-302 study (NCT01871727) support the BLA. In the study, I/ONTAK, a purified and more bioactive formulation of previously marketed denileukin diftitox (ONTAK), demonstrated anti-tumor activity without increasing toxicity. No new safety signals were observed with the agent, according to topline results.1,2

"The acceptance of the previously announced BLA submission for I/ONTAK is another important regulatory milestone for our oncology program. With an anticipated PDUFA date of September 28, 2023, we look forward to the potential approval of this therapeutic for patients with persistent or recurrent cutaneous T-cell lymphoma, a rare disease for which patients with advanced disease have limited treatment options," stated Leonard Mazur, chairman and chief executive officer of Citius, in a press release.1

E7777-G000-302 is multi-center, open-label, single-arm study. Patients who were enrolled in the study had persistent or recurrent CTCL, were diagnosed with Mycosis Fungoides or Sézary Syndrome, and their tumor tested positive for expression of the CD25 subunit of the IL-2 receptor.3

In 2 parts, investigators of E7777-G000-302 aimed to determine the maximum-tolerated dose of I/ONTAK by the occurrence of dose-limiting toxicities. The other primary end point of the study is objective response rate. Secondary end points explored in the study include duration of response, time to response, overall response rate (ORR), the number of patients with adverse events (AEs), the number of patients with serious AEs, and other efficacy outcomes.

Seventy-one patients were included in the study overall, and 69 patients were a part of the primary efficacy analysis set. The ORR in the overall population was 36.2% (95% CI, 25.0%-48.7%) per independent review committee. The clinical benefit rate observed was 53.5% (95% CI, 41.3%-65.5%). The ORR in the primary efficacy analysis set was 42.3% (95% CI, 30.6%-54.6%) with a CBR of 49.3% (95% CI, 37.0%-61.6%).2

The rate of AEs and serious AEs were consistent with the safety profile observed with the prior formulation of the drug. The most common AEs included nausea, fatigue, increased alanine aminotransferase, chills, and peripheral oedema.

Full results from the study of I/ONTAK in patients with persistent or recurrent CTCL will be presented during the upcoming 64th American Society of Hematology Annual and Exposition.1

REFERENCES:

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 5, 2022. https://bit.ly/3iHpzI0

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, Inc. April 6, 2022. Accessed December 5, 2022. https://bit.ly/3Bb9Bwo

3. A trial of E7777 in persistent and recurrent cutaneous t-cell lymphoma. ClinicalTrials.gov. Updated January 25, 2022. Accessed December 5, 2022. https://www.clinicaltrials.gov/ct2/show/NCT01871727?term=NCT01871727&draw=2&rank=1