- Clinical Trials
- Research News
- Industry Trends
- Agency Actions
- Drug Safety Issues
- Approvals, Launches, & New Indications
- Health Care Reform
Phase III Studies: Ruxolitinib (Jakavi) Reduces Disease Burden in Patients With Myelofibrosis
Results sustained over 2 years (Dec. 11)
Long-term follow-up data have been announced from the COMFORT-I and COMFORT-II phase III trials in myelofibrosis. In these studies, treatment with ruxolitinib (Jakavi, Novartis) resulted in sustained reductions in spleen size, a hallmark of myelofibrosis, while also improving quality of life and extending overall survival compared with placebo or the best available therapy (BAT).
The study results were presented at the 54th American Society of Hematology (ASH) Annual Meeting and Exposition in Atlanta, Georgia.
A 2-year follow-up analysis of the COMFORT-II (COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Therapy II) trial showed that ruxolitinib was associated with sustained reductions in splenomegaly. Overall, 48% of patients treated with ruxolitinib achieved a reduction in spleen volume of 35% or greater, and the majority of reductions were sustained with continued treatment over 2 years. Ruxolitinib-treated patients also showed an overall survival advantage compared with patients receiving BAT (hazard ratio [HR]: 0.51; P = 0.041).
In the COMFORT-I trial, which compared ruxolitinib and placebo, researchers presented long-term follow-up data on the efficacy and safety of ruxolitinib. Similar to the results in COMFORT-II, ruxolitinib was associated with sustained reductions in spleen volume. The mean reduction in the ruxolitinib arm was 32% at week 24, and this effect was maintained through week 96 (35%). The study demonstrated a continued overall survival benefit in favor of ruxolitinib, with survival rates of 83% and 73%, respectively, for ruxolitinib and placebo (HR: 0.58; P = 0.028) at week 102.
Myelofibrosis develops when uncontrolled signaling in the JAK pathway — which regulates the production of blood cells — causes bone marrow scarring and faulty blood cell production, resulting in severe complications.
Ruxolitinib is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases. The drug’s recommended starting dosages are 15 mg twice daily for patients with a platelet count between 100,000 cubic millimeters (mm3) and 200,000 mm3, and 20 mg twice daily for patients with a platelet count of greater than 200,000 mm3. The maximum recommended starting dosage in patients with platelet counts between 50,000/mm3 and 100,000/mm3 is 5 mg twice daily, and patients should be titrated cautiously.
Source: Novartis; December 11, 2012.