FDA has approved the supplemental New Drug Application for Iclusig (ponatinib) for adult patients with chronic-phase chronic myeloid leukemia with resistance or intolerance to at least two prior kinase inhibitors.
Iclusig is sponsored by Takeda Pharmaceutical Company Ltd.
The updated label includes an optimized, response-based ICLUSIG dosing regimen in CP-CML with a daily starting dose of 45 mg and, upon achieving ≤1% BCR-ABL1IS, dose reduction to 15 mg. This dosing regimen aims to maximize benefit-risk by providing efficacy and decreasing the risk of adverse events, including arterial occlusive events.
The sNDA approval is based on data from the phase II OPTIC (Optimizing Ponatinib Treatment In CML) trial, as well as five-year data from the phase II PACE (Ponatinib Ph+ ALL and CML Evaluation) trial.
The OPTIC trial included patients with CP-CML whose disease was highly-resistant to their immediate prior TKI, the majority of whom (65%) did not achieve a response greater than complete hematological response on immediate prior therapy.
At 12 months, 42% of 88 patients utilizing the newly approved response-based dosing regimen (45 mg to 15 mg) achieved ≤1% BCR-ABL1IS, the primary endpoint of OPTIC, and at a median follow up time of 28.5 months, 73% of these patients maintained their response. In these patients, 13% experienced an AOE of any Grade, 7% experienced Grade 3 or higher. Risk factors such as uncontrolled hypertension or diabetes should be managed, and caution should be exercised when treating patients with active or substantial history of clinically significant, uncontrolled cardiovascular disease.
