Takeda's Iclusig wins first-line FDA nod to treat rare Philadelphia chromosome-positive ALL

Twelve years after Takeda's Iclusig (ponatinib) earned a restricted FDA approval to treat certain patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL), the U.S. regulator has signed off on a wider use.

The new endorsement allows the drug to be used with chemotherapy for newly diagnosed, first-line patients with the disorder, Takeda said in a Tuesday release.

This is an accelerated approval from the agency and is contingent upon verification of clinical benefit in confirmatory trials. The nod makes Iclusig the first and only targeted therapy for these patients in the U.S., Takeda said.

Iclusig’s original nod a dozen years ago was for its use as a solo agent and was restricted to patients who could not receive other tyrosine kinase inhibitors (TKIs) or to those who were T315I-positive Ph+ALL.

“This label expansion for Iclusig is an incredibly exciting milestone,” Awny Farajallah, M.D., Takeda’s chief medical officer, said in a 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.”

The label expansion comes after Iclusig, a third-generation TKI, outperformed Novartis’ first-generation TKI Gleevec (imatinib) in a head-to-head trial of 245 patients who received one of the daily-dose drugs plus reduced intensity chemotherapy.

Of those who received Iclusig during a 12-week induction period, 34.4% had no detectable amount of disease—or any signs or symptoms of cancer—compared to 16.7% of those who were on Gleevec.

In the Iclusig group, 7% of patients discontinued treatment because of lack of efficacy compared with 26% in the Gleevec group.

“There has long been a need for a potent TKI that can suppress mutation development and elicit deep responses in the frontline,” Elias Jabbour, M.D., the lead investigator of the PhALLCON trial, said in the release. “Ponatinib may help address these factors and impact long-term outcomes.”

Ph+ALL is a rare disorder which affects approximately 25% of adult ALL patients in the U.S. and is characterized by the presence of the Philadelphia chromosome gene. In 2024, the American Cancer Society estimates there will be 6,550 new cases in the U.S. and 1,330 deaths from this extremely aggressive form of cancer.

Iclusig also is approved for patients with chronic-phase chronic myeloid leukemia with resistance or intolerance to at least two prior kinase inhibitors.

The drug was developed by Ariad Pharmaceuticals. In 2017, Takeda picked up the Massachusetts cancer specialist for $5.2 billion. Last month, the Japanese company reported (PDF) that Iclusig sales in the previous three quarters came to 41,460 million Japanese yen ($275 million).