FDA Approves Ruxolitinib for Steroid-Refractory Acute GVHD


The FDA has approved ruxolitinib for the treatment of adult and pediatric patients ≥12 years of age with steroid-refractory acute graft-versus-host disease.

The FDA has approved ruxolitinib (Jakafi) for the treatment of adult and pediatric patients ≥12 years of age with steroid-refractory acute graft-versus-host disease (aGVHD).

The approval is based on findings from the phase II REACH1 trial, which demonstrated that the combination of ruxolitinib with corticosteroids elicited a 57% overall response rate (ORR) at day 28 in patients with steroid-refractory aGVHD, with a complete response (CR) rate of 31%.

"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," Hervé Hoppenot, chief executive officer, Incyte, the developer of ruxolitinib, said in a press release. "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. We are proud of the impact Jakafi has had on patients’ lives to-date and are dedicated to advancing our ongoing research in JAK inhibition to serve more GVHD patients in the future."

In February 2019, the FDA added 3 months to the review period for a supplemental new drug application for this indication of the JAK1/2 inhibitor, making the new action date May 24, 2019. The extension period was to allow the agency to review additional data they had requested from Incyte.

The open-label, single-cohort, multicenter phase II REACH1 study accrued patients aged ≥12 years old who had received allogeneic hematopoietic stem cell transplantation and developed grade 2 to 4 steroid-refractory aGVHD. Patients had received up to 1 systemic treatment beyond corticosteroids for aGVHD. Of the 71 patients recruited on the trial, 49 patients were refractory to steroids alone, 12 patients had received ≥2 prior anti-GVHD therapies, and 10 patients did not otherwise meet the steroid-refractory definition by the FDA.

Ruxolitinib was administered at 5 mg twice daily, which could be increased to 10 mg twice daily if no cytopenias occurred. The primary endpoint was ORR at day 28; a key secondary endpoint was duration of response.

At the April 2, 2018, data cutoff for the primary analysis, 71 patients had received ≥1 dose of ruxolitinib. There was nearly an even number of male and female patients, and the mean age was 52.9 years (range, 18-73). At 28.2% each, acute myeloid leukemia and myelodysplastic syndrome were the most common primary malignancies.

Overall, 80.3% of patients received peripheral blood stem cells, 18.3% received bone marrow, and 1.4% received cord blood as the stem cell source. At baseline 32.4%, 47.9%, and 19.7% of patients had grade II, III, and IV aGVHD, respectively. Half (50.7%) of patients had ≥2 organs involved. At the data cutoff, treatment was ongoing in 23.9% of patients (n = 17).

Prior results showed that the ORR at day 28 was 54.9% (n = 39; 95%, CI, 42.7%-66.8%), which included a 26.8% (n = 19) complete response (CR) rate, a 9.9% (n = 7) very good partial response rate, and an18.3% (n = 13) partial response rate. Responses were observed regardless of grade or steroid-refractory criteria. The ORRs were 82.6% (19/23), 41.2% (14/34), and 42.9% (6/14), among patients with grade 2, 3, and 4 aGVHD, respectively.

Among the 39 patients who responded by day 28, the median duration of response had not been reached. The 3- and 6-month event-free survival probability estimates were 79.0% (95% CI, 62.3%-88.9%) and 67.0% (95% CI, 47.3%-80.7%), respectively. The median time to response was 7.0 days (range, 6-49).

The most commonly reported adverse events among all 71 patients were infections (55%) and edema (51%); the most common laboratory abnormalities were anemia (75%), thrombocytopenia (75%), and neutropenia (58%). Nine patients had cytomegalovirus infection, 4 had viremia, and 1 had chorioretinitis. Two patients died from sepsis and pulmonary hemorrhage) related to TEAEs.

"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," Madan Jagasia, MBBS, MS, MMHC, lead investigator on REACH1 trial and professor of medicine, Vanderbilt University Medical Center, Department of Medicine, Division of Hematology-Oncology and Chief Medical Officer, Vanderbilt-Ingram Cancer Center, said in the press release. "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."

Ruxolitinib was previously approved by the FDA as a treatment for patients with polycythemia vera who are intolerant of or have an inadequate response to hydroxyurea, as well as for the treatment of patients with intermediate or high-risk myelofibrosis.


  1. FDA Approves Jakafi (ruxolitinib) for the Treatment of Patients with Acute Graft-Versus-Host Disease. Incyte. Published May 24, 2019. https://bit.ly/2WiRktX?rel=0. Accessed May 24, 2019.
  2. The ongoing REACH program also includes the phase III REACH2 trial (NCT02913261), comparing ruxolitinib versus best available therapy in patients with corticosteroid-refractory aGVHD after ASCT, as well as the phase III REACH3 trial (NCT03112603) examining ruxolitinib versus best available therapy in patients with corticosteroid-refractory chronic GVHD after bone marrow transplantation. Jagasia M, Perales M-A, Schroeder MA, et al. Results from REACH1, a single-arm phase 2 study of ruxolitinib in combination with corticosteroids for the treatment of steroid-refractory acute graft-vs-host disease. Presented at: 2018 ASH Annual Meeting; December 1-4, 2018; San Diego, CA. Abstract 601.
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