FDA Approves Ponatinib for Resistant or Intolerant Chronic-Phase CML

FDA

The FDA has approved ponatinib (Iclusig) for the treatment of patients with chronic-phase chronic myeloid leukemia (CML) that is resistant or intolerant to at least 2 prior kinase inhibitors.

The updated label includes an optimized, response-based dosing regimen for this patient population that has a daily starting dose of 45 mg. Upon achieving ≤1% BCR-ABL1^IS, the dose is then reduced to 15 mg. With this regimen, the goal is to maximize the benefit-risk ratio by supplying efficacy and reducing the risk of toxicity in the form of arterial occlusive events (AOEs).

The regulatory decision is based on data from the phase 2 OPTIC and PACE trials.

“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, stated in a press release. “[Ponatinib] 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 [ponatinib].”

In the OPTIC trial, investigators enrolled patients with CP-CML whose disease was highly-resistant to the latest TKI they had received; 65% of these patients had not experienced a better response than that of a complete hematological response (CHR) on their immediate prior therapy.

Forty-two percent of 88 patients who received the response-based dosing regimen achieved at least a 1%BCR-ABL1^IS at 12 months, meeting the primary end point of the trial. Moreover, at a median follow-up of 28.5 months, 73% of these patients were noted to have maintained that response.

Regarding safety, 13% of patients reported any-grade AOE, with 7% of patients experiencing an event that was grade 3 or higher in severity. Risk factors like uncontrolled hypertension or diabetes should be appropriately managed, according to the FDA, and caution should be practiced when treating patients who have active or substantial history of clinically significant, uncontrolled cardiovascular disease.

Reference

US FDA approves supplemental new drug application for Takeda's ICLUSIG (ponatinib) for adult patients with resistant or intolerant chronic-phase CML. News release. Takeda Pharmaceutical Company Limited. December 18, 2020. Accessed December 18, 2020. http://bwnews.pr/3nCRuXm.