FDA Grants Full Approval to Denileukin Diftitox for Cutaneous T-Cell Lymphoma

Eisai Corporation of North America announced that the US Food and Drug Administration (FDA) has approved an efficacy supplemental biologics license application (sBLA) for denileukin diftitox (Ontak) solution for intravenous injection for the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma (CTCL) whose malignant cells express the CD25 component of the interleukin (IL)-2 receptor (CD25+). A separate efficacy supplement that included data from patients with CTCL whose malignant cells did not test positive for the CD25 component of the IL-2 receptor received a complete response letter.

Largest CTCL Trial of Its Kind

The FDA’s action, following a priority review, marks the conversion of an accelerated approval indication to full approval and is based on data from a phase III clinical trial that evaluated the overall efficacy and safety of denileukin diftitox in certain patients with CTCL. This trial was the largest phase III, randomized, double-blind, placebo-controlled trial ever conducted in CTCL.

The study met its primary endpoint of overall response rate (ORR), which was 46% for the 18 µg/kg/d dose of denileukin diftitox (P = .002 vs placebo) and 37% for the 9 µg/kg/d dose (P = .03 vs placebo) vs 15% for placebo. In addition, analysis of a secondary endpoint, progression-free survival (PFS), suggested a 73% reduction in risk of disease progression in the 18 µg/kg/d group (hazard ratio (HR) = 0.27, P = .0002) and a 58% reduction in risk of disease progression in the 9 µg/kg/d group (HR = 0.42, P = .02) compared to placebo.

“These data confirm the benefit of the safety and efficacy profiles of Ontak. We are also encouraged that the data indicate a significant reduction in risk of disease progression compared to placebo,” said Francine M. Foss, MD, professor of medicine at Yale Cancer Center.