The U.S. Food and Drug Administration (FDA) has granted approval to Lymphir (denileukin diftitox-cxdl) for the treatment of relapsed or refractory (r/r) cutaneous T-cell lymphoma (CTCL) in adult patients who have undergone at least one prior systemic therapy. This marks the first FDA-approved product for Citius Pharmaceuticals and a significant advancement in the CTCL treatment landscape.
Novel Immunotherapy Targeting IL-2 Receptor
Lymphir is a targeted immunotherapy designed to bind to the interleukin-2 (IL-2) receptor found on malignant T-cells and regulatory T cells (Tregs). This mechanism of action allows Lymphir to directly kill tumor cells and deplete Tregs, enhancing the body's immune response against the lymphoma. According to Dr. Myron Czuczman, Chief Medical Officer of Citius Pharmaceuticals, Lymphir's unique approach offers clinically meaningful benefits to a significant percentage of r/r CTCL patients.
Clinical Efficacy and Safety
The FDA's approval is based on data from the Phase 3 Pivotal Study 302, which evaluated Lymphir in CTCL patients who had previously received at least one systemic treatment. The primary efficacy population included 69 patients with stage I-III CTCL treated with denileukin diftitox-cxdl at a dose of 9 μg/kg/day. The study demonstrated an objective response rate (ORR) of 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 showing results after one to two cycles of treatment. Furthermore, 52% of patients maintained a duration of response for at least six months. Notably, 84.4% of skin evaluable subjects experienced a decrease in skin tumor burden, and 12.5% achieved complete clearing of skin disease. Pruritus, a common and distressing symptom of CTCL, showed clinically significant improvement in 31.7% of patients.
Lymphir's safety profile includes a boxed warning for capillary leak syndrome (CLS), a potentially life-threatening condition. Across three studies, the most common adverse reactions included increased transaminases, decreased albumin, nausea, edema, decreased hemoglobin, fatigue, musculoskeletal pain, rash, chills, constipation, pyrexia, and CLS.
Addressing Unmet Needs in CTCL Treatment
CTCL is a rare and chronic non-Hodgkin lymphoma primarily affecting the skin. Patients often experience debilitating skin lesions and severe itching, significantly impacting their quality of life. Current treatment options are limited, and patients typically cycle through various therapies as the disease progresses or becomes resistant. Lymphir offers a novel mechanism of action and a non-cross-resistant treatment option, providing hope for patients who have exhausted other therapies.
Dr. Francine Foss, Professor of Hematology and Director of the Multidisciplinary T-cell Lymphoma Program at Yale Cancer Center, emphasized the importance of controlling skin involvement in CTCL. "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," she stated.
Citius Oncology Launch
Following the FDA approval, Citius Pharmaceuticals has merged its oncology subsidiary with TenX Keane Acquisition to form Citius Oncology. This strategic move aims to focus on the commercialization of Lymphir and explore additional oncology assets. Citius Oncology will operate under a shared services agreement with Citius Pharma, led by Leonard Mazur, Chief Executive Officer, Jaime Bartushak, Chief Financial Officer, and Dr. Myron Czuczman, Chief Medical Officer.
"We believe a publicly traded Citius Oncology offers a unique pure play investment opportunity and is better positioned to unlock the value of Lymphir," said Mazur. The company anticipates launching Lymphir in the U.S. market within the next five months.
