FDA accepts license application of reformulated denileukin diftitox for patients with CTCL

January 2023 Pharma News Nalinee Pathak
Figure 2A.

The FDA has accepted a Biologics license application (BLA) for denileukin diftitox (I/ONTAK, Citius Pharmaceuticals) as a treatment option in patients with persistent or recurrent cutaneous T-cell lymphoma (CTCL). This application is based on the findings of a phase 3 study (NCT01871727).

Denileukin diftitox is an engineered cytotoxic fusion protein combining interleukin-2 (IL-2) and diphtheria toxin. The fusion protein has a high affinity for IL-2 receptors expressed on the surface of malignant cells. Once bound, it is taken up by the cell, releasing diphtheria toxin in the cytoplasm causing cell death. I/ONTAK is a reformulation (purified version) of ONTAK that received FDA approval in 2008 in patients with CTCL. However, ONTAK was voluntarily withdrawn from the US markets in 2014. A phase III study investigated I/ONTAK’s efficacy and safety.

The multicentre, single-arm, open-label, phase III study enrolled CD25-positive patients with a histopathological diagnosis of CTCL. The eligibility criteria included ECOG 0 to 2, acceptable bone marrow function and life expectancy of at least 3 months. The participants received prior treatment for their disease and a washout period of at least a month before receiving their treatment.

The first part of the study was done to determine the optimal dose of I/ONTAK in 21 patients. The participants received daily doses of I/ONTAK from 6 µg/kg to 15 µg/kg and determined 9 µg/kg daily as the optimal dose. In the next part of the study, 91 patients with CTCL received I/ONTAK (9 µg/kg daily) for 5 consecutive days every 21-day cycle.

The independent review committee (IRC) found an objective response rate (ORR) of 36.2% (95% CI, 25.0%-48.7%) with I/ONTAK treatment in the primary efficacy analysis set (n=69 patients). Further, the median duration of the response (DOR) and time to response (TTR) was 6.5 and 1.41 months, respectively. In the efficacy analysis set (n=71) an ORR of 42.3% along with DOR and TTR of 5.7 months and 1.41 months were reported.

The target action date is set on September 28, 2023.


Citius Pharmaceuticals Inc. announces U.S. Food and Drug Administration acceptance of biologics license application of denileukin diftitox for the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma.