FDA Accepts BLA Resubmission of Denileukin Diftitox for R/R CTCL

• The FDA has accepted Citius Pharmaceuticals' resubmitted biologics license application (BLA) for denileukin diftitox as a treatment for relapsed/refractory cutaneous T-cell lymphoma (CTCL).
• Denileukin diftitox (Lymphir) is an interleukin-2 (IL-2)-based immunotherapy with orphan drug designations for peripheral T-cell lymphoma (PTCL) and CTCL.
• A Prescription Drug User Fee Act (PDUFA) date of August 13, 2024, has been set.

The FDA has accepted the resubmission of the BLA for denileukin diftitox as a potential therapeutic option for patients with relapsed/refractory CTCL after at least 1 prior systemic therapy. The FDA has assigned a PDUFA date of August 13, 2024.

Previously on July 28, 2023, Citius Pharmaceuticals, Inc. received a complete response letter (CRL) for the BLA of denileukin diftitox stating additional manufacturing controls and enhanced product testing were needed. Then in September 2023, the FDA addressed the CRL and gave Citius Pharmaceuticals, Inc. the necessary actions required to support the resubmission of the BLA.

Now, the company believes that the enhanced product testing and additional manufacturing controls noted in the letter have been addressed. Further, no safety or efficacy issues were cited and there is no need for any additional clinical trials.

"The acceptance of the BLA resubmission reflects the completeness of our response to the enhanced product testing and additional controls highlighted by the FDA in their July 2023 CRL.No concerns relating to safety or efficacy were noted in the letter, and we remain confident in the robustness of the clinical data package included with the initial BLA submission," said Leonard Mazur, chairman and chief executive officer of Citius, in the press release.

Denileukin diftitox is an IL-2-based immunotherapy with orphan drug designations for peripheral T-cell lymphoma (PTCL) and CTCL. It was approved in Japan in 2021.

Data from a pivotal phase 3 study (NCT01871727) support the BLA as no new safety signals were identified when administered to patients with persistent or recurrent CTCL.² A total of 71 patients with stage I to III persistent or recurrent CTCL from the lead-in and main studies were assessed for efficacy, and 69 were included in the primary efficacy analysis set. An overall response rate (ORR) of 36.2%, (95% CI, 25.0%-48.7%) was demonstrated in 25 of the 69 patients, and an ORR of 42.3% was seen in 30 of the 71 patients (95% CI, 30.6%-54.6%).

For safety, rates of adverse events (AEs) and serious AEs were consistent with previously reported data. The most common AEs were nausea, fatigue, increased alanine aminotransferase, chills, and peripheral edema.

"We believe there remains a critical unmet need for an additional viable treatment option for patients with relapsed or refractory CTCL as current therapies are noncurative. We are grateful for the FDA's vital support for rare disease drug development as we work to expand treatment options for patients with cutaneous T-cell lymphoma. We look forward to the FDA's decision and the potential benefit [denileukin diftitox] may provide patients with relapsed or refractory CTCL," added Mazur in the press release.¹

REFERENCES:

1. Citius pharmaceuticals announces FDA acceptance of the BLA resubmission of LYMPHIR™ (denileukin diftitox) for the treatment of adults with relapsed or refractory cutaneous T-cell lymphoma. News release. Citius Pharmaceuticals, Inc. March 18, 2024. Accessed March 18, 2024. https://tinyurl.com/23x4zwnv

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. Citius Pharmaceuticals, Inc. April 6, 2022. Accessed March 18, 2024. https://prn.to/37pED7P