Syndax gets FDA okay for first-in-class leukaemia drug

A few days after a disappointing clinical trial readout for Syndax Pharma's Revuforj in one form of leukaemia, the company has claimed FDA approval in another.

The US regulator has cleared oral menin inhibitor Revuforj (revumenib) as a treatment for patients aged one and over with relapsed or refractory acute leukaemia with translocations in the KMT2A gene after a priority review, becoming the first FDA-backed treatment for this type of blood cancer.

It's the first regulatory approval for the drug, which will be launched before the end of this month, according to Syndax's chief executive, Michael Metzger.

It comes a few days after the company's shares came under pressure from the results of a phase 1/2 trial of Revuforj in relapsed or refractory mutant NPM1 acute myeloid leukaemia (AML), a follow-up indication, which hit its primary objective, but disappointed investors, who were concerned about the durability of its benefits.

NPM-1 mutations are seen in around 30% of AML cases, so it would be a major new indication for Revuforj, and shares in Syndax fell by nearly a quarter after the readout.

The approval of the first-in-class drug comes from the phase 1/2 AUGMENT-101 study, in which treatment with Revuforj resulted in 21% of patients going into complete remission (CR) or complete remission with partial haematological recovery (CRh).

The FDA extended its review by three months to allow it more time to look at the data filed by Syndax, but arrived at its decision a month ahead of the new 26th December deadline for the review.

Ghayas Issa, associate professor of leukaemia at the University of Texas MD Anderson Cancer Centre, said Revuforj is "a major breakthrough" for patients with this type of leukaemia and "represents a substantial improvement over what has been historically observed in these patients with previously available therapies."

Syndax's closest rival in the menin inhibitor category is Kura Oncology, whose ziftomenib candidate is due for in the registrational trial KOMET-001 trial in relapsed or refractory NPM1-mutant AML, with results due early next year.

Data from a phase 1a dose-escalation study of ziftomenib in NPM1-mutated and KMT2A-rearranged AML is due to be presented at this year's ASH congress.

Syndax is also preparing to give new data on Revuforj at the conference, including updated results from AUGMENT-101 and the phase 1/2 SAVE trial of the drug in combination with chemotherapy and AbbVie/Roche's BCL-2 inhibitor Venclexta (venetoclax) in KMT2A-rearranged, NPM1-mutated, or NUP98-rearranged AML.

Revuforj is Syndax's second first-in-class approval for 2024, coming after the company and partner Incyte got a green light from the FDA for anti-CSF-1R antibody Niktimvo (axatilimab) as a third-line or later treatment for chronic graft-versus-host disease (GVHD) in August.