FDA grants accelerated approval to ponatinib with chemotherapy for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia
Regulatory approval: On March 19, 2024, the FDA granted accelerated approval to ponatinib (Iclusig) with chemotherapy for adult patients with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL). Approval was supported by the phase III PhALLCON trial (NCT03589326), where minimal residual disease (MRD)–negative complete remission at end of induction was 30% with ponatinib vs 12% with imatinib plus chemotherapy (risk difference 0.18; p=0.0004).
FDA accelerated approval (regulatory news)
Date: 2024-03-19
The FDA granted accelerated approval to ponatinib (Iclusig) plus chemotherapy for adult patients with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL).
Supporting evidence
Efficacy was evaluated in PhALLCON (NCT03589326), a randomized, active-controlled, multicenter, open-label trial enrolling 245 adults with newly diagnosed Ph+ ALL. Patients were randomized 2:1 to:
- Ponatinib 30 mg orally once daily plus chemotherapy, or
- Imatinib 600 mg orally once daily plus chemotherapy (imatinib with chemotherapy is an unapproved regimen).
Chemotherapy included induction (vincristine + dexamethasone), consolidation (alternating methotrexate and cytarabine), and maintenance (vincristine + prednisone).
The primary efficacy basis for accelerated approval was MRD-negative complete remission (CR) rate at end of induction:
- 30% with ponatinib vs 12% with imatinib
- Risk difference 0.18 (95% CI: 0.08–0.28), p=0.0004
Dosing and safety highlights (label information)
Recommended ponatinib dose: 30 mg once daily, reduced to 15 mg once daily after induction upon achieving MRD-negative CR; continue with chemotherapy up to 20 cycles or until loss of response/unacceptable toxicity.
Common adverse reactions included hepatic dysfunction, arthralgia, rash, headache, pyrexia, GI events (abdominal pain, constipation, nausea, vomiting), fatigue, oral mucositis, hypertension, pancreatitis/elevated lipase, peripheral neuropathy, hemorrhage, febrile neutropenia, edema/fluid retention, paresthesia, and cardiac arrhythmias.
The review used RTOR, and the application received priority review and orphan drug designation.