Takeda Announces U.S. FDA Approval of Supplemental New Drug Application (sNDA) for Iclusig (ponatinib) in Adult Patients with Newly Diagnosed Ph+ ALL

OSAKA, Japan and CAMBRIDGE, Massachusetts, March 19, 2024 – Takeda (TSE:4502/NYSE:TAK) today announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) for Iclusig® (ponatinib) for the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy. This indication is approved under accelerated approval based on minimal residual disease (MRD)-negative complete remission (CR) at the end of induction. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. This accelerated approval application was granted Priority Review and evaluated under the Real-Time Oncology Review (RTOR) program, an FDA initiative designed to expedite the delivery of cancer medicines by allowing components of an application to be reviewed before submission of the complete application.

“This label expansion for Iclusig is an incredibly exciting milestone, allowing U.S. adult patients with newly diagnosed Ph+ ALL to have an approved, targeted treatment option in the frontline,” said Awny Farajallah, MD, chief medical officer, oncology at Takeda. “We are thrilled that the FDA has recognized the potential of Iclusig to fill a large gap in care for these patients and look forward to seeing the impact this can have on people with this rare and aggressive form of cancer.”

The approval was supported by data from the PhALLCON study – the first, global, Phase 3, registrational, head-to-head clinical trial in adults with newly diagnosed Ph+ ALL. The study, in which patients received either Iclusig or imatinib plus reduced-intensity chemotherapy, met its primary endpoint of MRD negative CR at the end of induction. MRD-negative CR is a composite endpoint defined in alignment with the FDA that reflects deep molecular and clinical responses and is an important prognostic indicator for long-term outcomes for patients with Ph+ ALL. Iclusig demonstrated superiority compared to imatinib, with patients who received Iclusig achieving a greater than two-fold improvement in the rate of MRD-negative CR at the end of induction (cycle 3). In the trial, the safety profile of Iclusig was comparable to imatinib, and no new safety signals were identified.

“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, MD, 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.”

Iclusig is a kinase inhibitor indicated in the U.S. for adult patients with newly diagnosed Ph+ ALL in combination with chemotherapy. This indication is approved under accelerated approval based on MRD-negative CR at the end of induction. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial(s). In addition, it is approved as monotherapy in Ph+ ALL for whom no other kinase inhibitors are indicated or T315I-positive Ph+ ALL, chronic-phase (CP) CML with resistance or intolerance to at least two prior kinase inhibitors, accelerated phase (AP) or blast phase (BP) CML for whom no other kinase inhibitors are indicated or T315I-positive CML (chronic phase, accelerated phase, or blast phase). Iclusig is not indicated and is not recommended for the treatment of patients with newly diagnosed CP-CML.

About the PhALLCON Trial

The PhALLCON study is a Phase 3, randomized, international, open-label multicenter trial evaluating the efficacy and safety of Iclusig versus imatinib in combination with reduced-intensity chemotherapy as a frontline therapy for adult patients with newly diagnosed Ph+ ALL.

A total of 245 patients were randomized 2:1 and treated with Iclusig or imatinib plus reduced-intensity chemotherapy. The median age of patients was 54 and 52 in the Iclusig and imatinib arms, respectively. 164 patients were treated with Iclusig receiving a starting dose of 30mg/day and 81 patients were treated with imatinib at a starting dose of 600mg/day. All patients received either Iclusig or imatinib with reduced-intensity chemotherapy through induction, consolidation and maintenance phase. After combination therapy, patients continued to receive single-agent Iclusig or imatinib until relapse from CR, progressive disease (PD), hematopoietic stem cell transplantation (HSCT), start of alternative therapy or unacceptable toxicity. The primary endpoint of the study was MRD-negative CR rate at the end of induction (3 cycles of treatment). Event-free survival, the key secondary endpoint of the trial, is not yet mature.

About Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)

Ph+ ALL is a rare form of ALL that affects approximately 25% of adult ALL patients in the U.S. 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 forms a longer chromosome 9 and a shorter chromosome 22, which leads to the development of BCR::ABL1 and is associated with Ph+ ALL.