Incyte, Syndax bag FDA approval for potential blockbuster Niktimvo in graft-versus-host disease

Incyte has expanded its graft-versus-host disease (GVHD) offerings beyond Jakafi.

The new addition comes from axatilimab, a CSF-1R inhibitor partnered with Syndax Pharmaceuticals. Wednesday, the drug received an FDA approval under the brand name Niktimvo to treat chronic GVHD (cGVHD) in patients who’ve failed at least two prior lines of systemic therapy.

Based on the drug’s stellar profile as a third-line treatment and potential to reach earlier lines of therapy, analysts at Leerink Partners have put Niktimvo’s peak sales at about $1 billion if everything goes right.

Niktimvo proved its worth in the phase 2 AGAVE-201 trial. Among patients who received the recommended dose at 0.3 mg/kg every two weeks, Niktimvo triggered an overall response rate of 75%. The median time to first response was 1.5 months, and the response lasted a median 1.9 months before disease progression, death or new systemic therapies. Among the responders, 60% of patients remained alive and didn’t need new systemic therapy for at least a year since the response.

It’s worth noting that Niktimvo showed decreased overall response rates at higher doses in the trial, which is not a common phenomenon in drug development.

“Despite recent advancements in the treatment of patients with chronic GVHD, there remains a significant unmet need for patients who progressed on earlier lines of therapy,” Incyte CEO Hervé Hoppenot said in a release back in February when the FDA accepted Niktimvo’s application and put it under priority review. “Axatilimab’s novel mechanism offers a differentiated treatment approach which may help patients suffering from this devastating disease.”

Niktimvo targets the CSF-1 receptor, a cell surface protein thought to mediate the activities of monocytes and macrophages, which are believed to play a role in the fibrotic disease process underlying cGVHD. Before Niktimvo, the FDA had approved Daiichi Sankyo’s Turalio as the first CSF-1R inhibitor but for a rare cancer called tenosynovial giant cell tumor.

Seeing the potential of the mechanism in GVHD, Incyte signed on with Syndax through a co-development and co-commercialization deal in 2021.

Third-line treatment is where Niktimvo is starting, but not where Incyte and Syndax plan to stop. The companies plan to initiate a phase 3 trial for Niktimvo and steroids, plus a phase 2 for Niktimvo and Jakafi, in first-line patients this year.

Thanks to an FDA approval in 2021, Incyte's Jakafi became available as a second- or third-line cGVHD therapy. Recently released three-year final analysis from the phase 3 REACH3 trial that originally supported that nod found Jakafi reduced the risk of treatment failure or death by 64% compared with best available treatment in steroid-refractory cGVHD. The trial didn’t see a significant difference in the risk of death between the two trial groups, although the finding was likely the result of about half of control group patients crossing over to Jakafi.

As Jakafi’s main indication of myelofibrosis faces competitive pressure, GVHD and polycythemia vera have become the JAK inhibitor’s main growth drivers lately.