FDA Approves Ponatinib To Treat Adult Patients with Resistant/Intolerant Chronic-Phase CML

The FDA approved the supplemental new drug application for ponatinib (Iclusig) to treat patients with chronic-phase chronic myeloid leukemia (CML) with resistance or intolerance to at least two prior kinase inhibitors.

The FDA approved the supplemental new drug application (sNDA) for ponatinib (Iclusig) to treat patients with chronic-phase chronic myeloid leukemia (CP-CML) with resistance or intolerance to at least 2 prior kinase inhibitors, according to Takeda Pharmaceutical Company.

This is an updated label for the agent, which now includes an optimized, response-based dosing regimen of ponatinib: a daily starting dose of 45 mg and, upon achieving ≤1% BCR-ABL1IS, dose reduction to 15 mg. According to Takeda, the dosing regimen aims to maximize benefit to risk associated with the drug, by providing efficacy and decreasing the risk of side effects.

“The FDA’s approval of this sNDA is a major milestone for the CML community. Though chronic-phase CML is often manageable, many patients still experience poor long-term outcomes and could benefit from a third-generation TKI earlier in their treatment journey,” Teresa Bitetti, president of global Oncology at Takeda said in a press release. “Iclusig is proven to be effective for many patients with resistant disease, and its use at the critical moment can lead to meaningful outcomes for these patients. We are excited about this updated label and believe it will help address gaps in care for patients with resistant or intolerant chronic-phase CML by optimizing treatment with Iclusig.”

The sNDA was based on data from the phase 2 OPTIC (Optimizing Ponatinib Treatment In CML) trial, as well as five-year data from the phase 2 PACE (Ponatinib Ph+ ALL and CML Evaluation) trial.

In the OPTIC trial, patients with CP-CML whose disease was highly resistant to their immediate prior TKI 42% of patients experienced ≤BCR-ABL1IS at 12 months. At a median follow-up of 28.5 months, 73% of these patients maintained their response. In this trial, 13% of patients treated with ponatinib experienced an arterial occlusive event (AOE) of any grade, with 7% experience a grade 3 AOE or higher.

In the PACE (Ponatinib Ph+ ALL and CML Evaluation) trial, researchers evaluated the agent in 449 patients with CML and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), who were resistant or intolerant to dasatinib (Sprycel) or nilotinib (Tasigna), or with the T315I mutation. In total, 55% of patients achieved major cytogenetic response by 12 months. Moreover, 70% of 64 patients with T315I-positive CP-CML achieved major cytogenetic response.

“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,” Takeda stated in the release.

“CML can be difficult to treat, particularly when patients have experienced resistance or intolerance to two or more TKIs. The revised indication allows physicians to consider Iclusig earlier in a course of treatment for chronic-phase CML patients, when it might provide the potential for the greatest benefit,” Dr. Jorge Cortes, director of the Georgia Cancer Center, said in the release. “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.”


Takeda. U.S. FDA Approves Supplemental New Drug Application for Takeda’s ICLUSIG® (ponatinib) for Adult Patients with Resistant or Intolerant Chronic-Phase CML. Published December 18, 2020. https://www.businesswire.com/news/home/20201218005716/en/U.S.-FDA-Approves-Supplemental-New-Drug-Application-for-Takedas-ICLUSIG®-ponatinib-for-Adult-Patients-with-Resistant-or-Intolerant-Chronic-Phase-CML. Accessed: December 18, 2020.