FDA approves drug for myelofibrosis

March 15, 2012

FDA approved ruxolitinib (Jakafi), a twice-daily tablet, indicated for the treatment of myelofibrosis, a rare bone marrow disease that affects less than 200,000 people in the United States.

Ruxolitinib(Jakafi, Incyte)

Efficacy

The primary efficacy end points were the proportion of patients who achieved a 35% or greater reduction in spleen volume from baseline, at 24 and 48 weeks for study 1 and study 2, respectively. In both studies, ruxolitinib was found to be more efficacious than placebo in study 1 (41.9% vs. 0.7%) and best available therapy in study 2 (28.5% vs. 0.0%).

Safety

The safety of ruxolitinib was evaluated in 6 clinical studies (n=617) over a median duaration of 10.9 months, involving (n=301) patients with myelofibrosis in 2 phase 3 studies. In clinical trials, the most common adverse events (occurring in >5%) included bruising, dizziness, headache, urinary tract infections, weight gain, and flatulence. Ruxolitinib may cause hematologic adverse reactions consisting of thrombocytopenia, anemia, and neutropenia.

A complete blood count (CBC) should be performed prior to initiation of therapy and every 2 to 4 weeks until doses are stabilized. Patients with a platelet count less than 200 X 109 /L will be more susceptible to developing thrombocytopenia. If thrombocytopenia does present while taking ruxolitinib, dosage reduction or discontinuation of treatment must be advised. Patients developing anemia may require blood transfusions and dosage modifications of ruxolitinib. Patients developing neutropenia (ANC less than 0.5 X 109 /L) should withhold ruxolitinib until symptoms resolve.

Risk of infection via bacteria, myobacteria, fungal, or viral should be assessed prior to initiation of ruxolitinib. If signs or symptoms of an infection are present, appropriate treatment should be initiated before starting ruxolitinib therapy. Clinicians should inform patients of early signs and symptoms of herpes zoster and advise patients to seek treatment.

Dosage

Prior to initiation of ruxolitinib, a CBC should be performed. The recommended initiation dose of ruxolitinib is 20 mg twice daily for patients with a platelet count greater than 200 X 109 /L or 15 mg twice daily in patients with a platelet count between 100 X 109 /L and 200 X 109 /L. A CBC should be performed every 2 to 4 weeks until doses are stabilized, and then administered as clinically indicated. If thrombocytopenia presents, the dose must be modified.

A maximum dose of 25 mg twice daily should be administered based on clinical response. Ruxolitinib should be discontinued if there is no spleen reduction or symptom improvement within 6 months of treatment.

Craig I. Coleman is associate professor of Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, Conn., and director of the Pharmcoeconomics and Outcomes Studies Group, Hartford Hospital.