FDA Approves First Drug to Treat Myelofibrosis

Get Permission

FDAlogoThe FDA has approved ruxolitinib (Jakafi), the first drug approved to specifically treat patients with the bone marrow disease myelofibrosis.

Myelofibrosis is a disease in which the bone marrow is replaced by scar tissue resulting in blood cells being made in organs such as the liver and the spleen. This disease is marked by an enlarged spleen, anemia, decreased white blood cells and platelets, and myelofibrosis-related symptoms. Symptoms include fatigue, abdominal discomfort, pain under the ribs, satiety, muscle and bone pain, itching, and night sweats.

Mechanism of Action

Ruxolitinib, taken orally twice daily, inhibits the enzymes JAK 1 and JAK 2, which are involved in regulating blood and immunologic functioning. Myelofibrosis is associated with the deregulation of JAK 1 and JAK 2.

“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.”

Two Clinical Trials

The safety and effectiveness of ruxolitinib was evaluated in two clinical trials with 528 patients. Patients in both trials were resistant or refractory to available myelofibrosis therapy or ineligible for allogeneic bone marrow transplantation. All patients had splenomegaly and were in need of treatment as a result of disease-related symptoms.

Patients in the studies were selected to receive treatment with ruxolitinib, placebo, or best available therapy (hydroxyurea, a chemotherapy agent, or glucocorticoids). A greater percentage of patients receiving ruxolitinib experienced more than a 35% reduction in spleen size compared to patients receiving placebo or best available therapy. Similarly, a greater proportion of patients receiving ruxolitinib saw more than a 50% reduction in myelofibrosis-related symptoms, including abdominal discomfort, night sweats, itching and bone or muscle pain, than was the case in patients receiving placebo.

The most serious side effects seen in patients treated with ruxolitinib include thrombocytopenia, anemia, fatigue, diarrhea, dyspnea, headache, dizziness, and nausea.

Ruxolitinib was reviewed under the 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 was approved ahead of the drug’s December 3 review goal date under the Prescription Drug User Fee Act and has been designated as an orphan drug, which identifies the disease as affecting fewer than 200,000 people in the United States.

The agent is manufactured by Incyte Corp of Wilmington, Delaware. ■