FDA approves sNDA for Ponatinib in adult patients with newly diagnosed Ph+ ALL

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About the Judgment

Test Name: A study of Ponatinib versus Imatinib in adults with acute lymphoblastic leukemia

ClinicalTrials.gov Identifier: NCT03589326

Sponsor: Takeda

Completion date (estimated): July 31, 2027

The FDA has approved a 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 is based on 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 monotherapy for patients who are not indicated for other kinase inhibitors or patients with Ph+ T3151-positive ALL, chronic myeloid leukemia (CML) in chronic phase with resistance or intolerance to at least 2 prior kinase inhibitors, phase accelerated or CML in blast phase for those who are not indicated for other kinase inhibitors or have T3151-positive CML.1

This tag extension for [ponatinib] is an incredibly exciting milestone, allowing adult US patients with newly diagnosed Ph+ ALL to have an approved targeted treatment option in the frontline, said Awny Farajallah, MD, Takeda’s medical director of oncology, in a press release . We are delighted that the FDA has recognized the potential of [ponatinib] to fill a huge gap in care for these patients and we 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 evaluated 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 daily of oral ponatinib with chemotherapy (n = 164) or 600 mg daily of oral imatinib with chemotherapy (n = 81) through induction, consolidation, and maintenance. After combination therapy, all patients continued to receive ponatinib or single-agent imatinib until relapse of complete remission (CR), progressive disease (PD), hematopoietic stem cell transplantation (HSCT), initiation of alternative therapy or unacceptable toxicity. The primary endpoint of the study is minimal residual disease (MRD) negative CR rate at the end of induction (3 cycles of treatment) and the secondary endpoint is event-free survival.1.2

According to study results, patients who were treated with ponatinib plus chemotherapy achieved the primary endpoint of MRD-negative CR at the end of induction. In addition, 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 safety profile comparable to that of imatinib, without identifying any new safety signals. Event-free survival results were immature, thus requiring further research to confirm these findings.1

The most common adverse events reported by those treated with ponatinib alone were rash, arthralgia, abdominal pain, headache, constipation, dry skin, hypertension, fatigue, fluid retention and edema, pyrexia, nausea, pancreatitis/elevation of lipase, bleeding, anemia. , liver 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 cell count.1

When used in combination with chemotherapy, patients reported experiencing liver dysfunction, arthralgia, rash and related conditions, headache, pyrexia, abdominal pain, constipation, fatigue, nausea, oral mucositis, hypertension, pancreatitis/elevation of lipase, peripheral neuropathy, haemorrhage, febrile neutropenia. , fluid retention and edema, vomiting, paresthesias and cardiac arrhythmias. Grade 3 or 4 laboratory abnormalities include decreases in white blood cell, neutrophil, platelet, lymphocyte, and hemoglobin counts, 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 the development of mutations and achieve deep responses in the frontline, said lead investigator Elias Jabbour, MD, University of Texas MD Anderson Cancer Center. in the press release. Ponatinib can help address these factors and affect long-term outcomes.1


1. Takeda. Takeda Announces US 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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