Iclusig gets FDA nod as frontline therapy for rare leukaemia

Takeda’s Iclusig has become the first targeted therapy approved by the FDA for use alongside chemotherapy as a first-line therapy for a rare form of acute lymphoblastic leukaemia (ALL).

The US regulator has cleared Iclusig (ponatinib) with reduced-intensity chemo for adult patients with newly diagnosed Philadelphia chromosome-positive ALL (Ph+ ALL), a fast-progressing blood cancer that makes up around a quarter of adult ALL cases.

It occurs when pieces of chromosomes 9 and 22 switch with each other to form abnormal structures and the development of the BCR-ABL1 kinase, which is targeted by Iclusig.

The accelerated approval draws on data from the PhALLCON trial, which compared Iclusig to imatinib – sold by Novartis as Glivec/Gleevec, but also available as a generic – and showed that Takeda’s drug was more effective at achieving a minimal residual disease-negative complete remission (MRD-negative CR). Imatinib is not approved for use with chemo in this patient group, but is used off-label.

The MRD-negative CR rate at the end of induction was 30% in the Iclusig arm and 12% with imatinib, with comparable safety, according to the FDA. Takeda’s drug is also the first therapy to be approved using MRD-negative CR as a primary endpoint.

Takeda acquired the third-generation tyrosine kinase inhibitor (TKI) as part of its $5.2 billion takeover of Ariad Pharma in 2017, part of a push into oncology by the Japanese pharma group under long-serving chief executive Christophe Weber. It is sold by Takeda in the US, recording sales of JPY 41.5 billion ($273 million) in the first nine months of 2023, with European rights held by Incyte and Angelini.

The drug is already approved by the FDA for chronic-phase chronic myeloid leukaemia (CML) who have failed treatment with at least two prior kinase inhibitors, accelerated-phase or blast-phase CML or Ph+ ALL in patients without any kinase inhibitor options, and CML and Ph+ ALL with the T315I resistance mutation.

“This label expansion for Iclusig is an incredibly exciting milestone,” said Awny Farajallah, chief medical officer of oncology at Takeda, who added: “We are thrilled that the FDA has recognised 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.”