FDA Sets Action Date for Resubmitted Lymphir in Rare Skin Cancer

The FDA has accepted the resubmission of the Citius Pharmaceuticals’ biologics license application (BLA) for Lymphir (denileukin diftitox), to treat patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy. The FDA has assigned a Prescription Drug User Fee Act goal date of Aug.13, 2024.

Cutaneous T-cell lymphoma is a type of cutaneous non-Hodgkin lymphoma (NHL), accounting for about 4% of all non-Hodgkin lymphoma, according to the American Cancer Society. In cutaneous T-cell lymphoma, T-cells, a type of lymphocyte that plays a role in the immune system, become cancerous and presents as red, scaly patches on the skin. It is more common among men than women, with an average age of onset between 50 and 60 years of age. It is generally a slow-growing cancer but in rare cases can spread to lymph nodes and internal organs.

Lymphir (previously called I/Ontak) is a recombinant fusion protein that combines interleukin-2 (IL-2) receptors with diphtheria toxin fragments. It binds to IL-2 receptors on the cell surface, causing diphtheria toxin fragments that have entered cells to inhibit protein synthesis.

The FDA had issued a complete response letter in July 2023, and the agency asked Citius to do enhanced product testing. The company said in a press release that it believes it has addressed enhanced product testing and additional manufacturing controls noted in the letter. There were no safety or efficacy issues cited and no additional trials required.

Ontak was marketed in the United States from 1999 to 2014, when it was voluntarily withdrawn from the market because of production issues related to the E. coli expression system and purification challenges. Citius official have said that manufacturing improvements resulted in a new formulation that maintains the same amino acid sequence but features improved purity and bioactivity.

The BLA is supported by a pivotal phase 3 study. The therapy demonstrated anti-tumor activity in the treatment of persistent or recurrent CTCL. It provided disease control and has an average time to response within one to two cycles of treatment in patients who have failed multiple prior therapies. An independent review committee determined the study achieved an objective response rate of 36.2% and an investigator efficacy analysis determined that the study achieved an objective response rate of 42.3%. Most common adverse events included: nausea, fatigue, increased alanine aminotransferase, chills and peripheral edema.