New Dosing, Safety Guidance for Myelofibrosis Drug

Nick Mulcahy

June 14, 2013

An update to the prescribing information for ruxolitinib (Jakafi, Incyte) includes new recommended dosing for patients with low platelet counts and a warning about a possible treatment-related risk for progressive multifocal leukoencephalopathy.

Ruxolitinib, which was approved by the US Food and Drug Administration (FDA) in 2011, is the first and only FDA-approved product for the treatment of patients with intermediate- or high-risk myelofibrosis.

"The expanded dosing guidance provides physicians with important new information intended to help patients with low platelet counts experience the clinical benefits of [ruxolitinib], including meaningful spleen reduction and symptom improvement," said Paul Friedman, MD, president and chief executive officer of Incyte Corporation.

For patients with baseline platelet counts from 50 to 100 × 10⁹/L (50,000 to 100,000/µL), the prescribing information now recommends a starting dose of 5 mg twice daily and the flexibility for subsequent dose modifications based on safety and efficacy.

The FDA decision to expand the dosing information comes after a review of the supplemental New Drug Application (sNDA).

The sNDA included data from an ongoing phase 2 trial of patients with baseline platelet counts of 50,000 to 100,000/µL. The starting dose in the trial is 5 mg twice daily, but it can be adjusted up or down, according to protocol-defined hematology criteria. The target dose is 10 mg twice daily to achieve clinical response.

The safety and efficacy findings from an interim analysis of Study 258 are generally consistent with the results observed in the pivotal phase 3 COMFORT-I and COMFORT-II program, according to a press statement from the company.

Results from those 2 trials were published last year in the New England Journal of Medicine (2012;366:787-798 and 799-807). At the time, one of the principal investigators told Medscape Medical News that, in her clinical experience, the "vast majority of patients" on ruxolitinib experience meaningful benefits in quality of life and symptom relief. However, another expert, writing in an accompanying editorial (N Engl J Med. 2012;366:844-846), said that ruxolitinib is suitable for only some patients with myelofibrosis, possibly as few as 25%, and has adverse events, including myelosuppression.

The updated prescribing information also has new information on an adverse event. "Progressive multifocal leukoencephalopathy (PML) has been reported with ruxolitinib treatment for myelofibrosis. If PML is suspected, stop [ruxolitinib] and evaluate," reads the document.

In addition, the Patient Counseling Information section now advises healthcare professionals to educate patients about the early signs and symptoms of PML.

According to the company, the new warning is based on "1 known case of PML with an undetermined relationship to ruxolitinib in the approximately 9800 myelofibrosis patients treated with ruxolitinib worldwide in clinical trials or with commercial product." The press statement also indicates that patients with myeloproliferative neoplasms, including myelofibrosis, might be at higher risk of developing PML.


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