FDA Approves Ruxolitinib for Chronic GVHD

Chronic graft-vs-host disease (GVHD) is a condition that can occur after an allogeneic stem cell transplant in which the donated cells initiate an immune response and attack the transplant recipient’s organs.

The FDA approved ruxolitinib to treat chronic graft-vs-host disease (GVHD) after failure of 1 or 2 lines of systemic therapy in adult and pediatric patients 12 years and older.

The Janus kinase (JAK) inhibitor, sold under the name Jakafi, is already approved for steroid-refractory acute GVHD in adults and adolescents.

GVHD is a condition that can occur after an allogeneic stem cell transplant (ASCT) in which the donated cells initiate an immune response and attack the transplant recipient’s organs. There are 2 major forms of GVHD: acute, which generally occurs within 100 days of transplant, and chronic, which generally occurs more than 100 days after transplant.

Both forms are associated with significant morbidity and mortality and can affect multiple organ systems.

The approval was based on the REACH3 study, a phase 3, randomized, open-label, multicenter study of ruxolitinib in comparison to best available therapy (BAT) for treatment of steroid-refractory chronic GVHD after ASCT. The primary end point of overall response rate (ORR) at week 24 (cycle 7 day 1) was 49.7% for the study drug compared with 25.6% for BAT (P <.0001).

The ORR through cycle 7 day 1 was 70% for Jakafi compared with 57% for BAT.

“GVHD is the leading cause of morbidity and mortality in patients following an allogeneic stem cell transplant, yet there historically have been limited treatment options available beyond first-line systemic therapies,” Steven Stein, MD, chief medical officer of Incyte, said in a statement.

The current standard of care are steroids, but nearly half of patients with chronic GVHD do not respond adequately, added Robert Zeiser, MD, University Medical Center Freiburg, Department of Hematology, Oncology and Stem Cell Transplantation, Freiburg, Germany, and the principal investigator of the REACH3 trial. The trial showed ruxolitinib “demonstrated significantly improved outcomes across a range of efficacy measures compared to best available therapy. This approval represents a significant advancement in the treatment of appropriate patients with chronic GVHD—for both the patients who face a poor prognosis and the healthcare providers who struggle to effectively treat them.”

“In the US, there are over 14,000 people living with chronic GVHD, many of whom face significant complications that may impair daily activities and linger for years,” said Susan Stewart, executive director, BMT InfoNet. “The approval of Jakafi is an exciting development for the GVHD community and an important step forward in the treatment of a disease with few options.”

The most common hematologic adverse reactions (incidence > 35%) were anemia and thrombocytopenia. The most common nonhematologic adverse reactions (incidence ≥ 20%) were infections (pathogen not specified) and viral infection.

Ruxolitinib's supplemental New Drug Application (sNDA) in chronic GHVD was reviewed under the FDA’s Priority Review program as well as the Project Orbis program, an initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology drugs among its international partners.

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