Citius Pharmaceuticals Resubmits BLA to FDA for Lymphir to Treat Cutaneous T-Cell Lymphoma

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Citius Pharmaceuticals, Inc. has resubmitted a biologics license application (BLA) to the FDA for Lymphir (denileukin diftitox-cxdl) to treat patients with relapsed/refractory cutaneous T-cell lymphoma (CTCL) after previous administration of at least one systemic therapy.¹ The initial BLA submitted to the FDA for the interleukin-2–based immunotherapy was issued a complete response letter in July 2023 seeking stronger product testing, as well as additional controls that were agreed on during the review of the application. The FDA did not cite concerns for the safety or efficacy of Lymphir.²

“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,” Leonard Mazur, chairman and CEO of Citius, said in a press release. “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.”¹

Lymphir is a recombinant fusion protein comprised of the interleukin-2 (IL-2) receptor binding domain and diphtheria toxin fragments. The drug inhibits protein synthesis by attaching to IL-2 receptors on the cell surface, allowing diphtheria toxin fragments that were able to gain entry into cells to interfere with this process. Lymphir was previously granted Orphan Drug Designation by the FDA in 2011 and 2013 for peripheral T-cell lymphoma and CTCL, respectively.

The resubmission of the BLA was based on findings from the pivotal Phase III Study 302 trial (NCT01871727). The trial’s primary endpoint was objective response rate (ORR), with secondary endpoints that included duration of response, time to response, skin response, duration of skin response, safety, and tolerability. Exploratory endpoints included progression-free survival, time to progression, pruritus improvement, and quality of life.³

Trial data show that Lymphir produced an ORR of 36.2% (n = 25/69; 95% CI, 25.0%-48.7%) based on an independent review committee assessment, whereas ORR per trial investigator assessment was 42.3% (n = 30/71; 95% CI, 30.6%-54.6%).³

Any-grade treatment-emergent adverse effects (TEAEs) were reported in 98.6% of patients, with serious TEAEs reported in 37.7% of patients. There were no fatal serious TEAEs reported.

"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,” Mazur said in the release. “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.”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. March 18, 2024. Accessed March 19, 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, 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 lymphoma. News release. Citius Pharmaceuticals, Inc. July 29, 2023. Accessed March 19, 2024. https://citiuspharma.com/investors/news-media/news/release-details/2023/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/default.aspx

3. 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 March 19, 2024. https://www.prnewswire.com/news-releases/citius-pharmaceuticals-reports-topline-data-from-the-pivotal-phase-3-study-of-cancer-immunotherapy-iontak-e7777-for-the-treatment-of-persistent-or-recurrent-cutaneous-t-cell-lymphoma-ctcl-in-support-of-bla-submission-301518707.html