FDA accepts BLA of denileukin diftitox reformulation for persistent or recurrent cutaneous T-cell lymphoma

The BLA was supported by data from the phase III Study 302 trial (E777-G000-302; NCT01871727), where I/ONTAK demonstrated an objective response rate (ORR) of 36.2% (95% CI, 25.0%-48.7%) per independent review committee (IRC) assessment in the 69 patients who comprised the primary efficacy analysis set. In this group, the median duration of response (DOR) was 6.5 months (range, 3.0+ to 23.5+), with a median time to response (TTR) of 1.41 months. The clinical benefit rate (CBR) was 49.3% (95% CI, 37.0%-61.6%).

Per investigator assessment, I/Ontak elicited an ORR of 42.3% (95% CI, 30.6%-54.6%) in the 71 patients who comprised the efficacy analysis set. In this group, the median DOR was 5.7 months (range, 0.7+ to 26.1+), the median TTR was 1.41 months, and the CBR was 53.5% (95% CI, 41.3%-65.5%). The Prescription Drug User Fee Act date is set for September 28, 2023.

I/Ontak is a recombinant fusion protein that combines the interleukin-2 (IL-2) receptor binding domain with diphtheria toxin fragments. The agent specifically binds to IL-2 receptors on the cell surface, causing diphtheria toxin fragments that have entered cells to inhibit protein synthesis. I/Ontak is a purified version of denileukin diftitox and a reformulation of I/Ontak, which was granted a full approval from the FDA in October 2008 for use in this CTCL patient population. The original formulation was voluntarily withdrawn from the United States market in 2014.