FDA Approves sNDA for Ponatinib in Adult Patients With Newly Diagnosed Ph+ ALL


The approval comes after positive results from the PhALLCON study, however, further research is needed to confirm immature event-free survival findings.

Acute lymphoblastic leukemia on notepad -- Image credit: Dzmitry | stock.adobe.com

Image credit: Dzmitry | stock.adobe.com

About the Trial

Trial Name: A Study of Ponatinib Versus Imatinib in Adults With Acute Lymphoblastic Leukemia

ClinicalTrials.gov ID: NCT03589326

Sponsor: Takeda

Completion Date (Estimated): July 31, 2027

The FDA has approved the supplemental new drug application (sNDA) for ponatinib (Iclusig; Takeda Pharmaceuticals) in combination with chemotherapy for the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The approval comes under an accelerated approval that is based on positive data from the PhALLCON study (NCT03589326).1

Ponatinib is a kinase inhibitor that can be used in combination with chemotherapy. It is also approved as a monotherapy for patients who are not indicated for other kinase inhibitors or patients with T3151-positive Ph+ ALL, chronic-phase chronic myeloid leukemia (CML) with either resistance or intolerance to at least 2 prior kinase inhibitors, accelerated phase or blast phase CML for those who are not indicated for other kinase inhibitors or have T3151-positive CML.1

“This label expansion for [ponatinib] is an incredibly exciting milestone, allowing US 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, in a press release. “We are thrilled that the FDA has recognized the potential of [ponatinib] 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

The PhALLCON study is a global, head-to-head phase 3 clinical trial that assessed treatment with ponatinib or imatinib plus chemotherapy for adult patients with newly diagnosed Ph+ ALL. A total of 245 patients were enrolled in the trial to receive 30 mg of daily oral ponatinib with chemotherapy (n = 164), or 600 mg of daily oral imatinib with chemotherapy (n = 81) through induction, consolidation, and maintenance phases. Following combination therapy, all patients continued to receive single-agent ponatinib or imatinib until relapse from complete remission (CR), progressive disease (PD), hematopoietic stem cell transplant (HSCT), start of alternative therapy, or unacceptable toxicity. The primary end point of the study is minimal residual disease (MRD)-negative CR rate at the end of induction (3 treatment cycles), and the secondary end point is event-free survival.1,2

According to the study results, patients who were treated with ponatinib plus chemotherapy met the primary end point of MRD-negative CR by the end of induction. Further, the results indicated that these patients achieved a response that was 2-times greater than those who received imatinib. The trial had also indicated that ponatinib had a comparable safety profile to imatinib, with no new safety signals being identified. Event-free survival results were immature, therefore, requiring further research to confirm these findings.1

The most common adverse events reported by those who received treatment with ponatinib alone were rash, arthralgia, abdominal pain, headache, constipation, dry skin, hypertension, fatigue, fluid retention and edema, pyrexia, nausea, pancreatitis/lipase elevation, hemorrhage, anemia, hepatic dysfunction, and arterial occlusive events. The most common grade 3 or 4 laboratory abnormalities consisted of decreases in platelet count, neutrophil cell count, and white blood cells.1

When used in combination with chemotherapy, patients reported experiencing hepatic dysfunction, arthralgia, rash and related conditions, headache, pyrexia, abdominal pain, constipation, fatigue, nausea, oral mucositis, hypertension, pancreatitis/lipase elevation, neuropathy peripheral, hemorrhage, febrile neutropenia, fluid retention and edema, vomiting, paresthesia, and cardiac arrhythmias. Grade 3 or 4 laboratory abnormalities included decreases in white blood cell count, neutrophil cell count, platelet count, lymphocyte cell count, and hemoglobin, as well as increases in lipase and alanine aminotransferase.1

“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 lead investigator Elias Jabbour, MD, University of Texas MD Anderson Cancer Center, in the press release. “Ponatinib may help address these factors and impact long-term outcomes.”1


1. Takeda. Takeda Announces U.S. FDA Approval of Supplemental New Drug Application (sNDA) for ICLUSIG® (ponatinib) in Adult Patients with Newly Diagnosed Ph+ ALL. 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. A Study of Ponatinib Versus Imatinib in Adults With Acute Lymphoblastic Leukemia. ClinicalTrials.gov identifier: NCT03589326. Updated October 27, 2023. Accessed March 19, 2024. https://clinicaltrials.gov/study/NCT03589326
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