FDA Grants Accelerated Approval to Ponatinib Plus Chemotherapy in First-Line Ph+ ALL

The FDA has granted accelerated approval to ponatinib (Iclusig; Takeda) plus chemotherapy for the first-line treatment of Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL), the agency announced today in a press release.¹

The approval was supported by efficacy data from the phase 3 PhALLCON study (NCT03589326), a randomized, active-controlled, multicenter, open-label trial including 245 adult patients with newly diagnosed Ph+ ALL. In 164 patients who received ponatinib in combination with chemotherapy, the minimal residual disease (MRD)–negative complete remission (CR) rate was 30%, compared with 12% among 81 patients who received imatinib (Gleevec; Novartis) plus chemotherapy. The risk difference was 0.18 (95% CI, 0.08-0.28; P = .0004).

“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,” Elias Jabbour, MD, The University of Texas MD Anderson Cancer Center and lead investigator of the PhALLCON trial, said in a statement.² “Ponatinib may help address these factors and impact long-term outcomes.”

FDA approval stamp | Image credit: Olivier Le Moal - stock.adobe.com

In the PhALLCON study, patients were randomized 2 to 1 to receive either 30 mg ponatinib once daily plus chemotherapy or 600 mg imatinib once daily plus chemotherapy, with the latter being an unapproved regimen.¹ Chemotherapy entailed 3 cycles of induction with vincristine and dexamethasone followed by 6 cycles of consolidation with alternating methotrexate and cytarabine, then 11 cycles of vincristine and prednisone maintenance. After the induction phase and upon MRD-negative CR, ponatinib was reduced to 15 mg daily.

The most common adverse events with ponatinib plus chemotherapy were hepatic dysfunction, arthralgia, rash and related conditions, headache, pyrexia, abdominal pain, constipation, fatigue, nausea, oral mucositis, hypertension, pancreatitis or elevated lipase, peripheral neuropathy, hemorrhage, febrile neutropenia, fluid retention and edema, vomiting, paresthesia, and cardiac arrhythmias.

Th supplemental new drug application for ponatinib plus chemotherapy was granted priority review and evaluated under the FDA's Real-Time Oncology Review program, which aims to expedite cancer medicine availability by allowing for the review of some components of an application ahead of submission of the complete application.²

Ponatinib was initially approved in 2012 and is also indicated as a monotherapy for the treatment of T315I-positive Ph+ ALL or for Ph+ ALL in patients for whom no other kinase inhibitors are indicated; for patients with chronic phase chronic myeloid leukemia (CML) who are resistant or intolerant to at least 2 prior kinase inhibitors; for accelerated- or blast-phase CML when no other kinase inhibitors are indicated; and for T315I-positive CML in the chronic, accelerated, or blast phase.³

“This label expansion for Iclusig is an incredibly exciting milestone, allowing US adult patients with newly diagnosed Ph+ ALL to have an approved, targeted treatment option in the front line,” Awny Farajallah, MD, chief medical officer, oncology at Takeda, said.² “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."

Reerences

1. FDA grants accelerated approval to ponatinib with chemotherapy for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. News release. 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

2. 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. Takeda. 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/

3. Iclusig. Prescribing information. Takeda; 2024. Accessed March 19, 2024. https://www.iclusig.com/sites/default/files/2023-02/iclusig-prescribing-information.pdf