Incyte sinks as itacitinib fails pivotal test in acute GVHD

A phase 3 trial of Incyte’s itacitinib in treatment-naive acute graft-versus-host disease (GVHD) has missed its primary endpoint, wiping around $2 billion off the biotech’s market cap. The failure of the JAK1 inhibitor is another blow to Incyte’s efforts to expand its commercial portfolio beyond Jakafi.

Incyte won FDA approval for Jakafi, an inhibitor of JAK1 and JAK2, in steroid-refractory acute GVHD last year, fueling optimism that the more selective itacitinib could succeed in related indications.

That idea was put to the test in a phase 3 trial that gave itacitinib and corticosteroids to patients with treatment-naïve acute GVHD. However, the trial found itacitinib was no more effective statistically than placebo when given alongside corticosteroids. The response rate in the itacitinib arm was 74%, compared to around 66% in the control group.

The difference between the response rates was too small to be statistically significant, causing the trial to miss its primary endpoint. Incyte also failed to find evidence that itacitinib has a positive effect on non-relapse mortality at six months, a key secondary endpoint.

Failure in acute, treatment-naïve GVHD wipes out the prospect of Incyte winning approval for the wholly owned asset in the near term. However, Incyte is continuing to test itacitinib in other, related indications. A phase 3 trial of itacitinib in chronic GVHD heads up a clutch of ongoing studies of the JAK1 inhibitor but data from that program are years away.

Incyte’s decision to keep going with the chronic GVHD study despite the failure in the acute setting reflects a belief that the two diseases have unique biology. Whether that means itacitinib is any more effective in chronic GVHD remains to be seen. Either way, itacitinib is now unlikely to quench Incyte’s thirst for another commercial asset any time soon. 

Itacitinib emerged as the next big hope for Incyte in the wake of setbacks to other drugs. Epacadostat looked set to be the next big immuno-oncology drug, only to fail in a pivotal trial and take the IDO field down with it. Olumiant came to market, but Incyte backed away from the drug—which is licensed to Eli Lilly—last year after safety concerns limited dosing and, by extension, its commercial potential. 

With Incyte's sizable R&D budget failing to deliver new products, pressure is mounting on the biotech.

"We believe the failure of GRAVITAS-301, which follows three prior high profile pipeline disappointments in four years, may lead some investors to question the company's ability to consistently generate value from R&D investment," analysts at SVB Leerink wrote in a note to investors.