JAK inhibitor reapproved by FDA

Incyte Inc. announced that the U.S. Food and Drug Administration (FDA) has approved its JAK inhibitor Jakafi (Ruxolitinib) for the treatment of chronic graft-versus-host disease (GVHD) in adults and children 12 years and older. These patients had received one or two systemic treatments. This is the latest indication for rucotinib after the FDA approved its topical formulation for the treatment of atopic dermatitis yesterday.

This approval is based on the results of a randomized, open-label Phase 3 clinical trial. The overall response rate (ORR) at 24 weeks was 49.7% in patients with hormone-resistant GVHD who received Jakafi compared with the best available treatment, significantly higher than in the control group (25.6%, P <0.0001). The study is in the New England Journal of Medicine.

GVHD is a potentially fatal complication that can occur after allogeneic stem cell transplantation. It is caused when transplanted cells initiate an immune response and attack the recipient organ. There are two main forms of GVHD: acute GVHD, which typically occurs within 100 days of transplantation; Chronic GVHD usually occurs 100 days after transplantation. Both forms can involve multiple organ systems, including the skin, gastrointestinal tract, and liver.

Jakafi is an oral "first-in-class" JAK1/JAK2 inhibitor. JAKs belong to a family of cytoplasmic tyrosine kinases whose function is to transmit signals mediated by cytokines such as interferon. JAK is also a major component of hematopoietic signaling and is overactivated in the early stage of GVHD. Inhibition of JAK1/JAK2 can inhibit the release of inflammatory cytokines, reduce the pathological process of GVHD, and also inhibit the activation of donor T cells and reduce the immune response. It was approved by the FDA in 2019 for the treatment of steroid-refractory acute GVHD. Incyte has development and marketing rights to Rucotinib in the U.S., while Novartis has development and marketing rights outside the U.S.