FDA Accepts Citius's Resubmitted BLA for Denileukin Diftitox for the Treatment of Adults with Relapsed or Refractory Cutaneous T-Cell Lymphoma

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Citius Pharmaceuticals recently announced¹ the US Food and Drug Administration (FDA) has accepted the resubmission of its Biologics License Application (BLA) for denileukin diftitox (Lymphir) for the treatment of relapsed or refractory cutaneous T-cell lymphoma (CTCL) in adults.

The FDA's acceptance of the resubmission follows Citius's resubmission last month² and a Complete Response Letter received in July 2023.³

Denileukin diftitox, an IL-2-based immunotherapy, targets patients who have undergone at least one prior systemic therapy for CTCL. The approval of the BLA is supported by results from a pivotal phase 3 study (NCT01871727)⁴ supporting denileukin diftitox's potential in this indication.

The trial aimed to evaluate the effectiveness of denileukin diftitox in participants with recurrent or persistent CTCL stages I to III, assessed by the objective response rate. The study was comprised of a lead-in dose-finding phase to determine the optimal dose of denileukin diftitox for efficacy and safety assessment.⁴

The multicenter, open-label study involved 2 main phases: a lead-in part and a main part. Participants transitioned through 3 phases while on the study: pretreatment, treatment, and extension, followed by a follow-up period.⁴

Enrolling 112 participants, the study began on May 30, 2013, and completed on December 14, 2021. Participants in the experimental arm received denileukin diftitox at a dose of 9 mcg/kg via intravenous infusion over 60 minutes on five consecutive days during each 21-day cycle.⁴

Following dialogue with the FDA, Citius believes it has successfully addressed the FDA's requests for enhanced product testing and additional manufacturing controls, without the necessity for additional trials, according to the news release.¹

"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 CEO of Citius, in a news release.¹ "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 non-curative. 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 LYMPHIR may provide patients with relapsed or refractory CTCL."

With its BLA acceptance, the FDA also assigned a Prescription Drug User Fee Act goal date of August 13, 2024.

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. PR Newswire. March 18, 2024. Accessed March 18, 2024. https://www.prnewswire.com/news-releases/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-302090911.html
2. Citius Pharmaceuticals resubmits the Biologics License Application of Lymphir (denileukin diftitox) for the treatment of adults with relapsed or refractory cutaneous T-cell lymphoma. News release. PR Newswire. February 14, 2024. Accessed March 18, 2024. https://www.prnewswire.com/news-releases/citius-pharmaceuticals-resubmits-the-biologics-license-application-of-lymphir-denileukin-diftitox-for-the-treatment-of-adults-with-relapsed-or-refractory-cutaneous-t-cell-lymphoma-302061089.html
3. Citius Pharmaceuticals, Inc. receives a Complete Response Letter from the U.S. Food and Drug Administration (FDA) for Lymphir (denileukin diftitox) for the treatment of patients with relapsed or refractory cutaneous T-cell lymphoma. News release. PR Newswire. July 29, 2023. Accessed March 18, 2024. https://www.prnewswire.com/news-releases/citius-pharmaceuticals-inc-receives-a-complete-response-letter-from-the-us-food-and-drug-administration-fda-for-lymphir-denileukin-diftitox-for-the-treatment-of-patients-with-relapsed-or-refractory-cutaneous-t-cell-lympho-301888813.html
4. A trial of E7777 in persistent and recurrent cutaneous T-cell lymphoma. ClinicalTrials.gov. Accessed March 18, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT01871727