FDA Approves Denileukin Diftitox-cxdl Immunotherapy for the Treatment of Adults With Relapsed or Refractory CTCL

The U.S. Food and Drug Administration (FDA) has approved denileukin diftitox-cxdl (Lymphir), a novel immunotherapy for the treatment of relapsed or refractory  cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.

 Citius Pharmaceuticals’ Lymphir is the only CTCL therapy that targets the interleukin-2 (IL-2) receptor found on malignant T-cells and Tregs. It is expected to launch within the next five months.

This is the first indication for Lymphir and the first FDA-approved product for Citius Pharma.

“This approval is a significant milestone for CTCL patients,” says Leonard Mazur, Chief Executive Officer of Citius Pharmaceuticals, in a news release. “The introduction of Lymphir with its potential to rapidly reduce skin disease and control symptomatic itching without cumulative toxicity, is expected to expand the CTCL treatment landscape and grow the overall market, currently estimated to be $300-$400 million,”

“As a treating oncologist, I have seen the profound negative effect on the quality of life in patients with r/r CTCL,” says Francine Foss, MD, Professor of Hematology and Director of the Multidisciplinary T-cell Lymphoma Program at Yale Cancer Center, New Haven, CT. “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. 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.”

The approval of Lymphir is based on results from the Phase 3 Pivotal Study 302 (NCT01871727) of CTCL patients who had previously received at least one systemic treatment. Actual study patients received a median of 4 (min, max: 1, 18) prior anticancer therapies. The primary efficacy population includes 69 patients with stage I-III CTCL who were treated with denileukin diftitox-cxdl (9 μg /kg/day). The primary efficacy outcome measure was Objective Response Rate (ORR), as assessed by an Independent Review Committee (IRC). The ORR was 36.2%, (95% CI: 25.0-48.7), with 8.7% achieving a Complete Response (CR).

The median time to response was rapid at 1.41 months, with the majority of responders (~70%) seeing results after 1–2 cycles of treatment. Duration of response was at least 6 months for 52.0% of the patients. 84.4% (54/64) of skin evaluable subjects had a decrease in skin tumor burden and 12.5% (8/64) saw complete clearing of skin disease. Pruritis was evaluated as an exploratory endpoint with 31.7% of patients demonstrating clinically significant pruritus improvement. Importantly, no cumulative toxicity was observed in patients receiving LYMPHIR.

Lymphir’s safety profile is consistent with the known safety profile for denileukin diftitox. Across three studies of 119 CTCL patients receiving 9 μg dose of denileukin diftitox, the most common (≥20%) adverse reactions, including laboratory abnormalities, were increased transaminases, albumin decreased, nausea, edema, hemoglobin decreased, fatigue, musculoskeletal pain, rash, chills, constipation, pyrexia, and capillary leak syndrome (CLS).

The U.S. Prescribing Information for Lymphir contains a boxed warning that CLS, including life-threatening or fatal reactions, can occur in patients receiving Lymphir. Monitor patients for signs and symptoms of CLS during treatment. Withhold Lymphir until CLS resolves, or permanently discontinue based on severity. Additional “Important Safety Information” is available below and Lymphir’s full prescribing information may be accessed here in the next few days.

This approval includes a postmarketing requirement from the FDA to characterize the risk of visual impairment in CTCL patients treated with Lymphir. Citius is committed to the safety of patients and will continue to monitor all safety data as it emerges.

Efficacy was established based on ORR, according to ISCL/EORTC Global Response Score (GRS) per Independent Review Committee (Olsen 2011). Efficacy results are shown in the table below.