FDA Approves Ruxolitinib for Steroid-Refractory Acute Graft-Versus-Host Disease

The FDA has approved ruxolitinib (Jakafi) for the treatment of steroid-refractory acute graft-versus-host disease (GVHD) in adult and pediatric patients 12 years and older.

Incyte said it is the first and only FDA-approved treatment for this indication. GVHD, a significant cause of morbidity and mortality in transplant recipients, can occur after an allogeneic transplant. In GVHD, the donated bone marrow or peripheral blood stem cells attack the body. The condition is very rare, occurring in fewer than 20,000 people in the United States each year.

“For the first time, patients with steroid-refractory acute GVHD, and the physicians that treat them, have an FDA-approved treatment for this serious disease,” said the company’s chief executive officer, Hervé Hoppenot, in a statement. “This approval is also an important milestone for Incyte, as it marks the third indication for Jakafi in the United States, further underscoring Incyte’s commitment to delivering innovative medicines for patients in need.”

Ruxolitinib is already approved for treatment of polycythemia vera in adults who have had an inadequate response to or are intolerant of hydroxyurea as well as intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF in adults.

The approval was based on data from REACH1, an open-label, single-arm, multicenter study of ruxolitinib in combination with corticosteroids in patients with steroid-refractory grade II to IV acute GVHD. Of the 71 patients recruited into REACH1, 49 patients were refractory to steroids alone, 12 patients had received 2 or more prior anti-GVHD therapies and 10 patients did not otherwise meet the FDA definition of steroid-refractory. Ruxolitinib was administered at 5 mg twice daily, and the dose could be increased to 10 mg twice daily after 3 days in the absence of toxicity.

The efficacy of ruxolitinib was evaluated based upon day 28 overall response rate (ORR), defined as a complete response (CR), very good partial response, or partial response based on the Center for International Blood and Marrow Transplant Research criteria.

The day 28 ORR in the 49 patients refractory to steroids alone was 57% with a CR rate of 31%. The most frequently reported adverse reactions among all 71 study participants were infections (55%) and edema (51%), and the most common laboratory abnormalities were anemia (75%), thrombocytopenia (75%), and neutropenia (58%).

GVHD is a condition that can occur after an allogeneic stem cell transplant (the transfer of stem cells from a donor) where the donated cells initiate an immune response and attack the transplant recipient’s organs, leading to significant morbidity and mortality. There are 2 major forms of GVHD, acute and chronic, that can affect multiple organ systems including the skin, gastrointestinal tract, and liver. Patients who develop steroid-refractory acute GVHD can progress to severe disease, with 1-year mortality rates of approximately 70%.

“Every year in the United States, about half of the people who develop acute GVHD do not respond adequately to steroids, making it an extremely challenging disease to treat,” said Madan Jagasia, MBBS, MS, MMHC, a lead investigator on the REACH1 trial, professor of medicine, Vanderbilt University Medical Center, Department of Medicine, Division of Hematology-Oncology, and chief medical officer, Vanderbilt-Ingram Cancer Center. “While allogeneic stem cell transplants have the potential to transform people’s lives, the onset of acute GVHD can significantly impact their prognosis. I am excited that we now have Jakafi as a new treatment option for acute GVHD patients that do not respond to corticosteroids who, until now, have had limited choices.”