The Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) for Iclusig® (ponatinib; Takeda) for adults with chronic-phase (CP) chronic myeloid leukemia (CML) with resistance or intolerance to at least 2 prior kinase inhibitors.
The sNDA approval is based on efficacy and safety data from the open-label phase 2 OPTIC trial and 5-year data from the phase 2 PACE trial. The OPTIC trial included 282 adults with CP-CML whose disease was considered to be resistant or resistant/intolerant to at least 2 prior kinase inhibitors or who had the T315I mutation. The PACE trial included 444 adults with CML and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) whose disease was considered to be resistant or intolerant to a prior kinase inhibitor.
Findings from the OPTIC trial showed that 42% (95% CI, 32-53) of 88 patients who received the 45mg starting dose achieved less than or equal to 1% BCR-ABL1IS at 12 months (primary end point). Moreover, 73% of responders maintained response at a median follow-up time of 28.5 months at the reduced dose of 15mg. Among these patients, 13% experienced an arterial occlusive event (AOE) of any grade and 7% experienced grade 3 or higher.
In the PACE trial, results demonstrated that 55% of 267 patients with CP-CML achieved major cytogenetic response (MCyR) at 12 months (primary end point), and 70% of 64 CP-CML patients with T315I+ achieved MCyR. In this trial, 26% of the 449 patients experienced AOEs.
The updated labeling also includes an optimized, response-based dosing regimen for Iclusig with a starting dose of 45mg orally once daily followed by a reduction to 15mg upon achieving less than or equal 1% BCR-ABL1IS. According to the Company, the new dosing regimen aims to maximize benefit to risk associated with Iclusig.
“As evidenced by the updated label, response-based dosing of Iclusig may allow patients to achieve the desired benefit that we know Iclusig can provide while reducing the risk for arterial occlusive events, a concern of physicians and, therefore, an important aspect of chronic-phase CML management,” said Jorge Cortes, MD, Director of the Georgia Cancer Center.
Iclusig, a kinase inhibitor, is already indicated for the treatment of chronic, accelerated, or blast phase CML or Ph+ ALL for whom no other tyrosine kinase inhibitor therapy is indicated. It is also approved for the treatment of adults with T315I+ CML (chronic, accelerated, or blast phase) or T315I+ Ph+ ALL.
For more information visit iclusig.com.
- U.S. FDA approves supplemental New Drug Application for Takeda’s Iclusig® (ponatinib) for adult patients with resistant or intolerant chronic-phase CML. [press release]. Cambridge, MA & Osaka, Japan: Takeda Pharmaceutical Company; December 18, 2020.
- Iclusig [package insert]. Cambridge, MA: Takeda Pharmaceutical Company; 2020.