Ruxolitinib is the first Janus kinase (JAK) inhibitor that was approved last year for the treatment of myelofibrosis. Data presented at ASH 2011 from the randomized pivotal COMFORT I trial of 309 patients with myelofibrosis showed a significant survival advantage with ruxolitinib compared with placebo: 24 patients in the placebo arm died during the study or during the extended follow-up compared with 13 ruxolitinib-treated patients, representing a 50% risk reduction with ruxolitinib.
In a post-hoc analysis of COMFORT II, which compared ruxolitinib with best available therapy in 219 patients, improvements in health-related quality of life were significantly greater in those receiving ruxolitinib. The greatest differences were reported in improvements in appetite loss, dyspnea, fatigue, insomnia, and pain.
“Myelofibrosis is a life-shortening disease, with symptoms that significantly compromise patients’ everyday lives,” said investigator Claire Harrison, MD, of Guy’s Hospital, London. “As a result, therapies that address the severe burden of myelofibrosis are urgently needed.”
CYT387 Promising in Anemia
Responding to this urgent need, the new JAK inhibitor, CYT387, is currently furthest along in development for myelofibrosis, demonstrating promising results.
The critical issue of this disease is anemia, according to Mark Kowalski, MD, PhD, Chief Medical Officer of YM BioSciences, the drug’s manufacturer. “Progressive anemia is a hallmark of this disease, with the consequence that many patients require frequent blood transfusions,” said Dr Kowalski. In addition, anemia is an indicator of poor life expectancy in this patient population.
In ongoing analyses of the phase 1/2 CYT387 dose-ranging trial in 166 patients with myelofibrosis, 54% of the 68 patients who were transfusion-dependent at baseline became transfusion-independent by 12 weeks. In addition, 65% of patients receiving 300 mg daily became transfusion-free. The mean duration of response exceeded 6 months. Phase 3 trials for CYT387 are slated to begin soon.—NC