RARE Daily

FDA Grants Accelerated approval for Takeda’s Ponatinib for Rare Blood Cancer

March 20, 2024

Rare Daily Staff

The U.S. Food and Drug Administration granted accelerated approval to Takeda’s Iclusig to expand its use to include a rare form of leukemia.

Iclusig is indicated for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). It won full approval in 2016 for CML and ALL.

Ph+ ALL is a rare form of ALL that affects approximately 25 percent of adult ALL patients in the United States and is characterized by the presence of an abnormal gene, known as the Philadelphia chromosome. In patients who are Philadelphia chromosome-positive (Ph+), an abnormal chromosome is formed when pieces of chromosomes 9 and 22 switch with each other. This leads to the development of BCR::ABL1 and is associated with Ph+ ALL.

Iclusig is a kinase inhibitor targeting BCR::ABL1, an abnormal tyrosine kinase that is expressed in CML and Ph+ ALL. Iclusig is a targeted cancer medicine specifically designed to inhibit the activity of BCR::ABL1 and its mutations. Iclusig inhibits native BCR::ABL1, as well as all BCR::ABL1 treatment-resistant mutations, including the most resistant T315I mutation. This mutation has been associated with resistance to all other approved tyrosine kinase inhibitors.

Efficacy was evaluated in PhALLCON, 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 Iclusig 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 completion of the induction phase and achievement of minimal residual disease-negative complete remission.

“Ph+ ALL is an extremely aggressive cancer and patients with this disease suffer from poor outcomes. There has long been a need for a potent TKI that can suppress mutation development and elicit deep responses in the frontline,” said Elias Jabbour, a physician with The University of Texas MD Anderson Cancer Center and lead investigator of the PhALLCON trial. “Ponatinib may help address these factors and impact long-term outcomes.”

Photo: Elias Jabbour, a physician with The University of Texas MD Anderson Cancer Center and lead investigator of the PhALLCON trial

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