Phase III trial of Jakafi (ruxolitinib) shows treatment advantages in myelofibrosis- Novartis

Novartis has announced that five-year treatment with Jakafi (ruxolitinib) suggested an overall survival advantage for patients with myelofibrosis (MF), despite crossover to Jakafi from the best available therapy arm after the primary analysis at 48 weeks (intent-to-treat analysis: 33% reduction in risk of death). In the COMFORT-II Phase III study, more than half of the patients with MF (53.4%) also experienced significant reductions (at least 35%) in spleen size with Jakafi therapy, and sustained this benefit over prolonged periods of time (median duration of 3.2 years).

COMFORT-II is a randomized, open-label, Phase III study of 219 patients with primary MF, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis in 56 study locations in Europe. Findings from this study were presented at the 57th American Society of Hematology Meeting.

Comment: Jakafi is approved to treat myelofibrosis but only provides symptomatic relief, mainly by reducing the size of a patient's enlarged spleen, a hallmark of the disease. JAK inhibitors, including ruxolitinib, are to date incapable of inducing complete or partial remissions, reversal of bone marrow fibrosis or molecular responses in myelofibrosis. This is consistent with the fact that JAK2 mutations are neither specific nor pathogenetically essential for the disease. Other currently available drugs in myelofibrosis are equally ineffective in terms of disease-modifying activity.