Fda Approval Summary Ruxolitinib For Treatment Of Steroid Refractory

On May 24, 2019, the Food and Drug Administration approved ruxolitinib for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in adult and pediatric patients 12 years and older. Approval was based on Study INCB 18424-271 (REACH-1; NCT02953678), an open-label, single-arm, multicenter trial that included 49 patients with grades 2-4 SR-aGVHD occurring after allogeneic hematopoietic stem cell transplantation. Ruxolitinib was administered at 5 mg twice daily, with dose increases to 10 mg twice daily permitted after 3 days in the absence of toxicity. The Day-28 overall response rate was 57.1% (95% confidence interval [CI]: 42.2-71.2). The median duration of response was 0.5 months (95% CI: 0.3-2.7), and the median time from Day-28 response to either death or need for new therapy for acute GVHD was 5.7 months (95% CI:... Common adverse reactions included anemia, thrombocytopenia, neutropenia, infections, edema, bleeding, and elevated transaminases.

Ruxolitinib is the first drug approved for treatment of SR-aGVHD. IMPLICATIONS FOR PRACTICE: Ruxolitinib is the first Food and Drug Administration-approved treatment for steroid-refractory acute graft-versus-host disease in adult and pediatric patients 12 years and older. Its approval provides a treatment option for the 60% of those patients who do not respond to steroid therapy. Keywords: Graft-versus-host disease; Hematopoietic stem cell transplantation; Ruxolitinib. Published 2019. This article is a U.S.

Government work and is in the public domain in the USA. Disclosures of potential conflicts of interest may be found at the end of this article. On May 24, 2019, the Food and Drug Administration approved ruxolitinib (JAKAFI, Incyte Corporation) for steroid-refractory acute graft-versus-host disease (GVHD) in adult and pediatric patients 12 years and older. Approval was based on Study INCB 18424-271 (NCT02953678), an open-label, single-arm, multicenter study of ruxolitinib that enrolled 49 patients with steroid-refractory acute GVHD Grades 2 to 4 (Mount Sinai Acute GVHD International Consortium criteria)... 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 trial’s primary endpoints were day-28 overall response rate (ORR) defined as complete response, very good partial response, or partial response by Center for International Blood and Marrow Transplant Research criteria, and the response...

Day-28 ORR was 100% for Grade 2 GVHD, 40.7% for Grade 3 GVHD, and 44.4% for Grade 4 GVHD. The median response duration, calculated from day-28 response to progression, new salvage therapy for acute GVHD, or death from any cause (with progression being defined as worsening by one stage in any organ without... In acute GVHD, the most common hematologic adverse reactions (incidence > 50%) are anemia, thrombocytopenia, and neutropenia. The most common nonhematologic adverse reactions (incidence > 50%) are infections and edema. The recommended starting dose of ruxolitinib for GVHD is 5 mg given orally twice daily. Corresponding author: Robert Q.

Le, Office of Hematology and Oncology Products, CDER, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA. Tel: 301-402-8320; Email: Robert.Le@fda.hhs.gov Received 2021 Nov 24; Accepted 2022 Jan 11; Collection date 2022 Jun. This work is written by (a) US Government employee(s) and is in the public domain in the US. On September 22, 2021, the Food and Drug Administration approved ruxolitinib for the treatment of chronic graft-versus-host disease (cGVHD) after the failure of one or two lines of systemic therapy in adult and pediatric...

Approval was based on Study INCB 18424-365 (REACH-3; CINC424D2301; NCT03112603), a randomized, open-label, multicenter trial of ruxolitinib in comparison to best available therapy (BAT) for the treatment of corticosteroid-refractory cGVHD occurring after the allogeneic... A total of 329 patients were randomized 1:1 to receive either ruxolitinib 10 mg twice daily (n = 165) or BAT (n = 164). BAT was selected by the investigator prior to randomization. The overall response rate through Cycle 7 Day 1 was 70% (95% CI, 63-77) in the ruxolitinib arm, and 57% (95% CI, 49-65) in the BAT arm. The median duration of response, calculated from first response to progression, death, or initiation of new systemic therapies for cGVHD, was 4.2 months (95% CI, 3.2-6.7) for the ruxolitinib arm and 2.1 months (95%... Common adverse reactions included anemia, thrombocytopenia, and infections.

Given the observed response rate with durability, the clinical benefit of ruxolitinib appears to outweigh the risks of treatment for cGVHD after the failure of one or two lines of systemic therapy. Keywords: ruxolitinib, graft-versus-host disease, hematopoietic stem cell transplantation On September 22, 2021, the Food and Drug Administration approved ruxolitinib (Jakafi, Incyte Corp.) for chronic graft-versus-host disease (cGVHD) after failure of one or two lines of systemic therapy in adult and pediatric patients... Efficacy was evaluated in REACH-3 (NCT03112603), a randomized, open-label, multicenter clinical trial of ruxolitinib compared to best available therapy (BAT) for corticosteroid-refractory cGVHD after allogeneic stem cell transplantation. The trial randomized 329 patients (1:1) to receive either ruxolitinib 10 mg twice daily or BAT. The major efficacy outcome used to support approval was overall response rate (ORR) (2014 NIH Response Criteria) through cycle 7 day 1.

The ORR was 70% (95% CI 63%, 77%) for the ruxolitinib arm and 57% (95% CI 49%, 65%) for the BAT arm with a difference in response rate of 13% (95% CI 3%, 23%). The median durations of response, calculated from first response to progression, death, or new systemic therapies for chronic GVHD, were 4.2 months (95% CI 3.2, 6.7) and 2.1 months (95% CI 1.6, 3.2) for... The median times from first response to death or new systemic therapies for cGVHD were 25 months (95% CI 16.8, NE) and 5.6 months (95% CI 4.1, 7.8) for the ruxolitinib and BAT arms,... In cGVHD, the most common (incidence > 35%) hematologic adverse reactions of ruxolitinib were anemia and thrombocytopenia. The most common (incidence ≥ 20%) nonhematologic adverse reactions were infections and viral infection. The recommended ruxolitinib starting dose for cGVHD is 10 mg given orally twice daily.

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