Ruxolitinib approved by the FDA for steroid refractory acute GvHD

The US Food and Drug Administration has approved ruxolitinib for patients aged 12 years and older with steroid refractory acute graft-versus-host-disease (aGvHD). Results of an open-label, single-arm, multicenter study showed that a combination of ruxolitinib with corticosteroids induced a 57% overall response rate (ORR), and a complete response (CR) of 31% at 28 days.

In February 2019, the FDA  added 3 months to the review period for the drug, to allow the agency to review additional data requested from the manufacturers, Incyte. The drug was previously approved by the FDA as treatment for patients with intermediate or high-risk myelofibrosis. 

The trial (NCT 02953678) enrolled 49 patients with steroid refractory aGvHD, grades II—IV, occurring after hematopoietic stem cell transplantation. The initial dose administered was 5mg, which could be increased to 10mg, after three days in the absence of toxicity.

The primary end-points of the study were ORR, CR, very good partial response (VGPR), or partial response (PR). On day 28, ORR was 100% for grade II GvHD, 40.7% for grade III, and 44.4% for grade IV GvHD. The median response duration was 16 days (95% CI; 9—83), and was calculated from day 28 response to progression, new salvage therapy for aGvHD or death from any cause. The median time from day 28 response to either death or need for new therapy for aGvHD, was 173 days (95% CI).

Common haematological adverse reactions in patients (>50% incidence) were anemia, thrombocytopenia, and neutropenia, with the most common nonhematologic adverse reactions being infections and edma (>50%).