FDA grants accelerated approval to Iclusig for Philadelphia chromosome-positive ALL
The FDA granted accelerated approval to ponatinib with chemotherapy for the treatment of adults with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia, according to a press release.
Ponatinib (Iclusig, Takeda) is a third-generation tyrosine kinase inhibitor developed to inhibit BCR::ABL1 with or without any single resistance mutation. The FDA granted priority review and orphan drug designation for the indication.
The agency based the accelerated approval on the results of the randomized phase 3 PhALLCON trial, which evaluated the efficacy and safety of reduced-intensity chemotherapy plus either ponatinib or imatinib as a front-line therapy for adults with newly diagnosed Philadelphia chromosome-positive ALL.
The study included 245 adults (median age, 54 years; 37% aged 60 years or older) with newly diagnosed Philadelphia chromosome-positive ALL.
Study investigators randomly assigned patients in a 2:1 ratio to ponatinib 30 mg daily — reduced to 15 mg upon achievement of a minimal residual disease (MRD)-negative complete response (CR)— or imatinib 600 mg daily with reduced-intensity chemotherapy through the end of induction, consolidation and post-consolidation.
After post-consolidation, study participants received ponatinib or imatinib monotherapy, with treatment continuing until unacceptable toxicity or disease progression.
Researchers observed an MRD-negative CR rate of 30% at the end of induction therapy in the ponatinib arm and 12% in the imatinib arm (risk difference, 0.18; 95% CI, 0.08-0.28).
The most common adverse reactions reported during the study included hepatic dysfunction, arthralgia, rash and related conditions, headache, pyrexia, abdominal pain, constipation, fatigue, nausea, oral mucositis, hypertension, pancreatitis/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 following achievement of an MRD-negative CR at the end of induction therapy. Ponatinib in combination with chemotherapy can then be continued for up to 20 cycles until either loss of response or unacceptable toxicity.
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