Lymphir Approved for Cutaneous T-cell Lymphoma

The U.S. Food and Drug Administration (FDA) approved Citius Pharmaceutical’s Lymphir^™ (denileukin diftitox-cxdl) on August 7, 2024. Lymphir is an IL-2 receptor-directed cytotoxin indicated for the treatment of adults with relapsed or refractory cutaneous T-cell lymphoma (r/r CTCL) that are in Stages I-III and the patient has tried at least one prior systemic treatment. Lymphir works by fusing diphtheria toxin (DT) into cancerous cells that express the IL-2 receptor, causing these cancer cells to die. Given as an intravenous (IV) infusion, the recommended dose is 9mcg/kg/day on days one through five of a 21-day cycle until disease progression or unacceptable toxicity. The label carries a boxed warning that Lymphir can cause capillary leak syndrome (CLS), including life-threatening reactions. Lymphir will be launched within the next five months. The price has not yet been announced. For full prescribing details, see here.

At a Glance

• Brand Drug: Lymphir (denileukin diftitox-cxdl)
• Manufacturer: Citius Pharmaceuticals
• Date Approved: August 7, 2024
• Indication: for the treatment of adult patients with relapsed or refractory Stage I-III CTCL after at least one prior systemic therapy
• Dosage Forms Available: single-dose vials containing 300mcg of denileukin diftitox-cxdl for reconstitution
• Launch Date: Within the next five months
• Estimated Annual Cost: Not yet announced
• Lymphir works by fusing diphtheria toxin (DT) to cancerous cells that express the IL-2 receptor. After the DT fragment is absorbed into the cancerous cells it inhibits protein synthesis causing cell death in immunosuppressive regulatory T lymphocytes (Tregs) and malignant T-cells.
• CTCL is a type of non-Hodgkin lymphoma (NHL) that affects the skin. It can take on various forms and is the most common type of cutaneous lymphoma. In CTCL, T-cells, which are a type of white blood cell involved in the immune system, become cancerous and lead to the development of skin lesions. This can cause severe pain and itching, significantly reducing the quality of life for patients with this disease.
• CTCL can take several years to more than ten years to advance to the tumor stage. Once it reaches this stage, the cancer becomes highly malignant and can spread to the lymph nodes and internal organs, leading to a poor prognosis. Due to the prolonged duration of the disease, patients usually undergo treatment with different medications to manage its progression.
• Each year, around 2,500 to 3,000 patients receive a CTCL diagnosis, with an estimated 40,000 individuals living with the disease.
• Approval was granted based on a phase III study, in which previously treated CTCL patients had a 36% Objective Response Rate (ORR) with 8.7% achieving a Complete Response (CR), as assessed by an Independent Review Committee (IRC).
• Lymphir carries a boxed warning indicating that it can cause CLS including life-threatening reactions. CLS occurs when blood plasma leaks outside of the blood vessel walls. In clinical trials, CLS occurred when patients had two or more symptoms including hypotension, swelling, and low albumin blood levels <3g/dL.
• CTCL can be treated with skin-directed therapies like ultraviolet light, topical corticosteroids, and topical retinoids, as well as systemic therapies including extracorporeal photopheresis, interferons, and targeted medications like Adcetris^® (brentuximab vedotin injection – Seagen) and Poteligeo^® (mogamulizumab-kpkc – Kyowa Kirin). Allogeneic stem cell transplants may be attempted for aggressive or unresponsive cases to cure CTCL.