Citius Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has approved Lymphir (denileukin diftitox-cxdl) for the treatment of relapsed or refractory cutaneous T-cell lymphoma (CTCL) in adult patients who have received at least one prior systemic therapy. Lymphir is the only CTCL therapy targeting the interleukin-2 (IL-2) receptor found on malignant T-cells and Tregs.
Clinical Efficacy and Safety
The approval of Lymphir is based on the Phase 3 Pivotal Study 302 (NCT01871727), an open-label, single-arm, multicenter trial. The study included patients with relapsed or refractory Stage I to IV CTCL who had expression of CD25 on ≥ 20% of biopsied malignant cells. Patients received Lymphir at 9 mcg/kg as an intravenous infusion daily for five days of each 21-day cycle.
The primary efficacy population consisted of 69 patients with Stage I-III CTCL. These patients had received a median of 4 prior anticancer therapies. 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 1.41 months, with approximately 70% of responders seeing results after 1–2 cycles of treatment. Duration of response was at least 6 months for 52.0% of the patients. Among skin evaluable subjects, 84.4% (54/64) had a decrease in skin tumor burden, and 12.5% (8/64) saw complete clearing of skin disease. Pruritus was evaluated as an exploratory endpoint, with 31.7% of patients demonstrating clinically significant improvement. No cumulative toxicity was observed.
Lymphir's safety profile is consistent with the known safety profile for denileukin diftitox. Common adverse reactions (≥20%) included increased transaminases, decreased albumin, nausea, edema, decreased hemoglobin, fatigue, musculoskeletal pain, rash, chills, constipation, pyrexia, and capillary leak syndrome (CLS).
Mechanism of Action
Lymphir is a targeted immune therapy that combines the IL-2 receptor binding domain with diphtheria toxin fragments. It binds to IL-2 receptors on the cell surface, causing diphtheria toxin fragments to inhibit protein synthesis, leading to cell death. Denileukin diftitox-cxdl depletes immunosuppressive regulatory T lymphocytes (Tregs) and exhibits antitumor activity through direct cytocidal action on IL-2R-expressing tumors.
Cutaneous T-Cell Lymphoma (CTCL) Context
CTCL is a rare type of non-Hodgkin lymphoma that primarily affects the skin. Approximately 2,500-3,000 patients are diagnosed each year, with an estimated 40,000 living with the disease. Patients with relapsed or refractory CTCL have limited treatment options. Reducing skin plaques and controlling itching without cumulative toxicity are primary goals of CTCL treatment.
Expert Commentary
Dr. Francine Foss, Professor of Hematology and Director of the Multidisciplinary T-cell Lymphoma Program at Yale Cancer Center, stated, "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."
Postmarketing Requirement
The 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 monitoring all safety data.
