FDA Approval of New Indication (December 2020)
In December 2020, the U.S. FDA approved the supplemental New Drug Application (sNDA) for Iclusig (ponatinib) for the treatment of adult patients with chronic‑phase chronic myeloid leukemia (CP‑CML) who are resistant or intolerant to at least two prior kinase inhibitors.
Updated Dosing Regimen
The updated drug label includes an optimized, response‑based dosing regimen for CP‑CML:
Starting dose: 45 mg
Dose reduction to 15 mg when ≤1% BCR‑ABL1IS is achieved
This regimen is designed to maximize the benefit‑risk profile by maintaining efficacy while reducing the risk of adverse events (AEs), including arterial occlusive events (AOEs).
Basis for Approval
The sNDA approval was based on data from the Phase 2 OPTIC trial (Iclusig in CML) and 5‑year data from the Phase 2 PACE trial (Iclusig in Ph+ ALL and CML).
Efficacy and Safety Results from OPTIC Trial
In 88 patients treated with the newly approved response‑based regimen (45 mg reduced to 15 mg):
At 12 months, 42% of patients achieved ≤1% BCR‑ABL1IS
During a median follow‑up of 28.5 months, 73% of patients maintained response
Any‑grade AOEs occurred in 13% of patients
Grade ≥3 AOEs occurred in 7% of patients
Efficacy and Safety Results from PACE Trial
The PACE trial enrolled patients with Ph+ ALL and CML who were resistant/intolerant to dasatinib or nilotinib, or harbored the T315I mutation. A total of 449 patients received Iclusib at a starting dose of 45 mg daily.
93% had received ≥2 prior TKIs; 56% had received ≥3 prior TKIs
Among 267 CP‑CML patients, 55% achieved major cytogenetic response (MCyR) at 12 months (primary endpoint)
Among 64 patients with T315I mutation, 70% achieved MCyR
AOEs occurred in 26% of 449 patients
Current Approved Indications for Iclusig
Iclusig is indicated for:
1.Adult patients with CP‑CML who are resistant or intolerant to at least two prior kinase inhibitors
2.Adult patients with accelerated‑phase (AP) or blast‑phase (BP) CML and adult patients with Ph+ ALL for whom no other kinase inhibitor is available
3.Adult patients with T315I‑positive CML (CP, AP, BP) or T315I‑positive Ph+ ALL
Iclusig is not indicated or recommended for the treatment of newly diagnosed CP‑CML patients.
