FDA Rejects BLA for Therapy to Treat Rare Skin Cancer

The FDA has issued a complete response letter to Citius Pharmaceuticals for its biologics license application (BLA) seeking approval for Lymphir (denileukin diftitox), an engineered IL-2-diphtheria toxin fusion protein to treat patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL).

The agency is asking Citius to do enhanced product testing and include additional controls. Company officials said in a press release there were no concerns relating to the safety and efficacy or with the prescribing information.

Leonard Mazur

“We intend to provide additional data and remain fully engaged with the FDA as we continue to work toward approval. We remain confident in the potential of Lymphir to become an important addition to the treatment landscape for patients with relapsed or refractory CTCL and make a meaningful difference in their lives,” Leonard Mazur, chairman and CEO of Citius, said in the press release.

Cutaneous T-cell lymphoma is a type of cutaneous non-Hodgkin lymphoma (NHL) that comes in a variety of forms. In CTCL, T-cells, a type of lymphocyte that plays a role in the immune system, become cancerous and develop into skin lesions.

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.

Ontak was marketed in the United States from 1999 to 2014, when it was voluntarily withdrawn from the market because of production issues related to the E. coli expression system and purification challenges.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.