FDA Approves Denileukin Diftitox for Adults With Relapsed or Refractory Cutaneous T-Cell Lymphoma

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Editor's Note: A previous version of this article stated that dermatologists "will not be able to prescribe" denileukin diftitox-cxdl. This has been corrected--dermatology clinicians will be able to prescribe.

The US Food and Drug Administration (FDA) has approved Citius Pharmaceuticals’ denileukin diftitox-cxdl (Lymphir) for adults with relapsed or refractory cutaneous T-cell lymphoma (CTCL).¹ Denileukin diftitox is a first of its kind treatment for CTCL that specifically targets the interleukin-2 (IL-2) receptor on both malignant T-cells and regulatory T-cells.

Approval of the IL-2-based immunotherapy, intended for patients who have undergone at least 1 prior systemic therapy for CTCL, is supported by positive phase 3 data (NCT01871727).² The multi-center, open-label study demonstrated its effectiveness among participants with recurrent or persistent CTCL stages I to III.

Participants received treatment intravenously over the course of 60 minutes for 5 consecutive days every 21 days. The primary outcomes included assessing dose-limiting toxicities, maximum tolerated dose, and overall response rate. Secondary outcomes focused on response duration, time to response, adverse events, and pharmacokinetic parameters. The study also evaluated the presence of anti-IL-2 antibodies and measured skin response in participants.²

In March, the FDA accepted Citius’ Biologics License Application for denileukin diftitox,³ following the issuance of a Complete Response Letter from the FDA in July 2023⁴ and the company’s subsequent February resubmission.⁵

"We are grateful to the clinicians, patients, and researchers who contributed to the development of Lymphir. We believe Lymphir's unique IL-2 receptor-targeted treatment, which kills tumor cells directly, and concurrently depletes host Tregs in order to boost the body's immune response, is an important differentiator and offers clinically meaningful benefits to a significant percentage of r/r patients," said Myron Czuczman, MD, chief medical officer of Citius in a news release.¹

"As the only IL-2 receptor-targeted immunotherapy for CTCL, Lymphir provides a novel and non-cross-resistant treatment option without cumulative toxicity for Stage I-III r/r patients for whom symptomatic skin involvement interferes with their daily quality of life," Czuczman said. "Lymphir's median time-to-response of only 1.4 months (min, max: 0.7, 5.6) offers many patients rapid skin relief."

Dermatology clinicians will be able to prescribe denileukin diftitox-cxdl to their patients with CTCL and should work collaboratively with a multidisciplinary care team involving oncologists, hematologists, and radiation therapists, among others.

"As a treating oncologist, I have seen the profound negative effect on the quality of life in patients with r/r CTCL. Given the long-term nature of the disease, pruritus, ulceration of the tumors, and secondary pyogenic skin infection, it is vital to get this skin involvement under control," said Francine Foss, MD, professor of hematology and director of the Multidisciplinary T-cell Lymphoma Program at Yale Cancer Center.¹ "Lymphir is the first therapeutic option in many years to offer hope of reducing skin disease, bringing us one step closer to filling the need for CTCL patients, particularly those that are not able to complete or continue prior therapies."

References

1. Citius Pharmaceuticals receives FDA approval for Lymphir (denileukin diftitox-cxdl) immunotherapy for the treatment of adults with relapsed or refractory cutaneous T-cell lymphoma. News release. PR Newswire. August 8, 2024. Accessed August 8, 2024. https://www.prnewswire.com/news-releases/citius-pharmaceuticals-receives-fda-approval-for-lymphir-denileukin-diftitox-cxdl-immunotherapy-for-the-treatment-of-adults-with-relapsed-or-refractory-cutaneous-t-cell-lymphoma-302217630.html
2. A trial of E7777 in persistent and recurrent cutaneous T-cell lymphoma. Clinicaltrials.gov identifier: NCT01871727. Updated December 12, 2022. Accessed August 6, 2024. https://clinicaltrials.gov/study/NCT01871727
3. 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 August 6, 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
4. 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 August 6, 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
5. 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 August 6, 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