Ruxolitinib Gains FDA Approval for Bone Marrow Disease

On November 16, 2011, the FDA approved ruxolitinib (Jakafi) as the first drug to specifically treat patients with myelofibrosis, a bone marrow disease.

Ruxolitinib is an oral JAK1 and JAK2 inhibitor typically prescribed in 15 mg to 20 mg doses twice daily. Deregulation of these pathways is responsible for myelofibrosis, a condition in which scar tissue replaces healthy bone marrow. Because of the bone marrow’s inability to generate new blood cells, the liver and spleen become responsible for producing new blood cells. The spleen often becomes enlarged in these patients. Other health issues associated with myelofibrosis include anemia, night sweats, and muscle and bone pain.

The FDA approved the drug based on the results of 2 clinical trials that evaluated 528 patients. In both trials, the patients were resistant or refractory to existing myelofibrosis therapy or ineligible for bone marrow transplantation. All patients had enlarged spleens.

In the first study, the phase III Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment (COMFORT-I), patients were divided into a ruxolitinib arm and a placebo arm. The first study showed that 41.9% of patients receiving ruxolitinib had at least a 35% reduction in spleen size, compared to only 0.7% of patients receiving the placebo by week 24 of the study (P <.0001). In this study, 45.9% of patients receiving ruxolitinib reported a reduction in symptoms compared to 5.3% of patients in the placebo arm.

In the COMFORT-II study, 28.5% of patients in the ruxolitinib arm experienced a 35% or greater reduction in spleen size. No patients receiving best available therapy (ie, hydroxyurea, a chemotherapy agent, or glucocorticoids) experienced the same kind of reduction (P <.0001). The median response time was 12 weeks.

“Jakafi represents another example of an increasing trend in oncology where a detailed scientific understanding of the mechanisms of a disease allows a drug to be directed toward specific molecular pathways,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “The clinical trials leading to this approval focused on problems that patients with myelofibrosis commonly encounter, including enlarged spleens and pain.”

Side effects associated with ruxolitinib included low blood platelet levels, anemia, fatigue, diarrhea, shortness of breath, headache, dizziness, and nausea. Recent studies have also suggested that serious adverse events may occur in patients who stop taking the drug. A long-term follow-up with patients was published in the New England Journal of Medicine in October. The study showed that 11% of patients who were taking ruxolitinib who stopped taking the drug required hospitalization related to drug cessation.

Jakafi will be marketed by Incyte Corporation of Wilmington, Delaware.