Ruxolitinib Approved to Treat the Bone Marrow Disease MyelofibrosisOn November 16, the Food and Drug Administration (FDA) approved ruxolitinib (Jakafi) for patients with intermediate- or high-risk myelofibrosis. Ruxolitinib is the first drug approved specifically to treat patients with this bone marrow disease.
In patients with myelofibrosis, fibrous tissue replaces the bone marrow, causing blood cells to be made in organs such as the liver and the spleen. This disease is marked by an enlarged spleen, anemia, and decreased numbers of white blood cells and platelets. Symptoms include fatigue, abdominal discomfort, pain under the ribs, feelings of fullness, muscle and bone pain, itching, and night sweats.
Myelofibrosis and other myeloproliferative disorders are associated with the increased activity of tyrosine kinase enzymes called JAK 1 and 2, which play key roles in a signaling pathway that is involved in cell proliferation and growth, hematopoiesis, and the immune response. Ruxolitinib, a pill taken twice daily, binds to and inhibits JAK 1 and 2, which may lead to reduced inflammation and cell proliferation.
The safety and effectiveness of ruxolitinib were evaluated in two clinical trials with a total of 528 patients. Patients in both trials had myelofibrosis that was resistant or refractory to available myelofibrosis therapy or ineligible for allogeneic bone marrow transplantation. All patients had enlarged spleens and needed treatment for disease-related symptoms. Patients in one study received ruxolitinib or the best available therapy; in the other study patients received ruxolitinib or a placebo. The primary endpoint in both trials was the proportion of patients whose spleen size was reduced by at least 35 percent.
In both studies, a significantly higher proportion of patients taking ruxolitinib saw their spleen shrink by 35 percent or more—29 percent of patients receiving ruxolitinib compared with zero percent of those receiving the best available therapy, and 42 percent of patients taking the drug compared with 1 percent of those taking the placebo. In the placebo-controlled study, a greater proportion of patients receiving ruxolitinib than receiving the placebo had their myelofibrosis-related symptoms reduced by 50 percent.
The most serious side effects seen in patients treated with ruxolitinib include low blood platelet levels, anemia, fatigue, diarrhea, shortness of breath, headache, dizziness, and nausea.
Ruxolitinib was reviewed under FDA’s priority review program, an expedited 6-month review of drugs that may offer significant advances in treatment over available therapy or that provide a treatment when no adequate therapy exists.
The treatment has been designated an orphan drug, a designation given to drugs for the treatment of diseases affecting fewer than 200,000 people in the United States.
NCI Cancer Bulletin for November 29, 2011 - National Cancer Institute