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FDA Grants Accelerated Approval to Takeda's Iclusig for Ph-Positive Acute Lymphoblastic Leukemia


Label expansion approval for Iclusig (ponatinib) addresses adult patients with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia.

Image credit: jarun011 | stock.adobe.com

Image credit: jarun011 | stock.adobe.com

The FDA has granted accelerated approval to Takeda’s supplemental New Drug Application for Iclusig (ponatinib) plus chemotherapy to treat adults with newly diagnosed Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia (ALL).1,2 Iclusig is the only pan-mutational, third-generation tyrosine kinase inhibitor (TKI) that targets BCR::ABL1, an abnormal tyrosine kinase expressed in Ph-positive ALL and chronic myeloid leukemia (CML). Iclusig can also treat all known single, treatment-resistant mutations, including T315I.

“This label expansion for Iclusig is an incredibly exciting milestone, allowing US adult patients with newly diagnosed Ph-positive ALL to have an approved, targeted treatment option in the frontline,” Awny Farajallah, MD, chief medical officer, oncology at Takeda, said in a press release. “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.”1

Ph-positive ALL is a rare disease that affects approximately 25% of adults with ALL in the United States. Ph-positive ALL is characterized by the presence of the abnormal Philadelphia chromosome gene. Patients with the disease have an abnormal chromosome that forms when pieces of chromosomes 9 and 22 switch places, which causes a longer chromosome 9 and a shorter chromosome 22, leading to the development of BCR::ABL1.3

Iclusig is a targeted therapy that was specifically developed to limit the activity of BCR::ABL1 and its mutations. The drug inhibits native BCR::ABL1 and all BCR::ABL1 treatment-resistant mutations. Iclusig was initially approved by the FDA in November 2016 for adults with chronic-phase (CP) CML who have resistance or intolerance to at least two prior TKIs, accelerated-phase (AP) or blast-phase (BP) CML or Ph-positive ALL for whom no other TKI is indicated, and T315I-positive CML (CP, AP or BP) or T315I-positive Ph-positive ALL.

The FDA based the accelerated approval on data from the randomized, active-controlled, multicenter, open-label Phase III PhALLCON trial (NCT03589326). Investigators enrolled patients with newly diagnosed Ph-positive ALL (n = 245) who were randomly assigned at a 2:1 ratio to receive 30 mg of oral Iclusig once daily or 600 mg of oral Gleevec (imatinib) plus chemotherapy.

The results showed that patients administered Iclusig in addition to chemotherapy (n = 164) experienced a minimal residual disease (MRD)–negative complete remission (CR) rate of 30% at the end of induction compared with 12% of patients administered Gleevec plus chemotherapy (n = 81), which translates to a risk difference of 0.18 (95% CI, 0.08-0.28; P = .0004).

Among patients administered Iclusig, 79% achieved a CR at the end of induction compared with 63% of patients administered Gleevec. A subset of patients who were not administered pre-phase therapy, MRD-negative CR was achieved by 31% of patients administered Iclusig compared with 16% of patients administered Gleevec, with 84% and 61% of these patients, respectively, achieving a CR at the end of induction. Median duration of follow-up in the Iclusig cohort was 20.4 months (95% CI, 18.4-23.9) compared with 18.1 months (95% CI, 13.9-24.3) among patients administered Gleevec.

In terms of safety, 71% of patients administered Iclusig required dose interruptions or reductions related to adverse effects (AEs), with 63% of patients experiencing serious AEs and 13% having AEs that led to permanent discontinuation of the drug.

“Ph-positive 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,” PhALLCON trial lead investigator Elias Jabbour, MD, The University of Texas MD Anderson Cancer Center, said in a press release. “[Iclusig] may help address these factors and impact long-term outcomes.”1


1. Takeda Announces U.S. FDA Approval of Supplemental New Drug Application (sNDA) for ICLUSIG® (ponatinib) in Adult Patients with Newly Diagnosed Ph+ ALL. Takeda. News release. March 19, 2024. Accessed March 19, 2024. https://www.takeda.com/newsroom/newsreleases/2024/takeda-announces-us-fda-approval-of-drug-for-iclusig-ponatinib-in-adult-patients/

2. FDA grants accelerated approval to ponatinib with chemotherapy for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. FDA. March 19, 2024. Accessed March 19, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-ponatinib-chemotherapy-newly-diagnosed-philadelphia-chromosome

3. Phase 3 Trial of ICLUSIG® (ponatinib) Met Primary Endpoint in Newly-Diagnosed Ph+ ALL, a Setting with No Targeted Treatments Approved in the US. Takeda. News release. November 16, 2022. Accessed March 19, 2024. https://www.takedaoncology.com/news/news-releases/phase-3-trial-of-iclusig-ponatinib-met-primary-efficacy-endpoint-in-frontline-ph-all-where-no-other-targeted-treatments-are-currently-approved-in-the-us/

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