On March 19, 2024, the U.S. Food and Drug Administration (FDA) granted accelerated approval to ponatinib (Iclusig®) with chemotherapy for adult patients with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL).
Efficacy was evaluated in PhALLCON (NCT03589326), a randomized, active-controlled, multicenter, open-label trial of 245 adult patients with newly diagnosed Ph+ ALL. Patients were randomized 2:1 to receive either ponatinib 30 mg orally once daily or imatinib 600 mg orally once daily with chemotherapy (imatinib with chemotherapy is an unapproved regimen). Chemotherapy consisted of 3 cycles of induction with vincristine and dexamethasone, 6 cycles of consolidation alternating between methotrexate and cytarabine, and 11 cycles of maintenance with vincristine and prednisone. The ponatinib dose was reduced to 15 mg once daily after patients completed the induction phase and achieved minimal residual disease (MRD)–negative complete remission (CR).
Efficacy was based on the MRD-negative CR rate at the end of induction, which was 30% in the ponatinib arm and 12% in the imatinib arm (risk difference = 0.18; 95% CI = 0.08, 0.28; p = 0.0004).
The most common adverse reactions reported during the clinical trial were hepatic dysfunction, arthralgia, rash and related conditions, headache, pyrexia, abdominal pain, constipation, fatigue, nausea, oral mucositis, hypertension, pancreatitis or elevated lipase, peripheral neuropathy, hemorrhage, febrile neutropenia, fluid retention and edema, vomiting, paresthesia, and cardiac arrhythmias.
The recommended ponatinib dose is 30 mg orally once daily with a reduction to 15 mg orally once daily upon achievement of MRD-negative CR at the end of induction. Continue ponatinib with chemotherapy for up to 20 cycles until patients experience a loss of response or unacceptable toxicity. For a description of dosing agents administered with ponatinib, see the prescribing information.
This review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted priority review and orphan drug designation. FDA-expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.
For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact the Oncology Center of Excellence’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.