In November 2011, the U.S. FDA approved ruxolitinib phosphate for the treatment of patients with intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF. Patients with intermediate and high-risk MF represent 80-90% of MF patients. Myelofibrosis is a potentially life-threatening blood cancer that belongs to a group of diseases referred to as myeloproliferative neoplasms. MF has a poor prognosis and limited treatment options. While the exact prevalence of MF is uncertain, Incyte believes MF affects about 16,000 to 18,500 people in the U.S. Ruxolitinib is the first and only product to be approved by the FDA for MF, and a first-in-class Janus-associated kinase (JAK1/JAK2) inhibitor. The FDA approval was based on results from two randomized phase III trials (COMFORT-I and COMFORT-II), which demonstrated that patients treated with ruxolitinib experienced significant reductions in splenomegaly.

The COMFORT-I trial compared ruxolitinib to placebo in 309 patients with primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF. The trial met the primary endpoint, showing that 41.9% of patients treated with the agent experienced a 35% or greater reduction in spleen volume at 24 weeks, compared with 0.7% of patients taking placebo. A 35% reduction in spleen volume correlates to approximately a 50% reduction in spleen size on palpation. COMFORT-I also demonstrated improvements in symptoms as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) v.2.0 electronic diary and the MFSAF Total Symptom Score (TSS) comprised of six specific symptoms (abdominal discomfort, pain under the left ribs, an early feeling of fullness, night sweats, bone and muscle pain and itching), all of which contributed to the overall benefit. At week 24, the percentage of patients with a 50% or greater improvement in the TSS was 45.9% and 5.3% in patients treated with ruxolitinib and placebo, respectively, with a median time to response of less than four weeks. In the COMFORT-I study, the efficacy of ruxolitinib was observed regardless of JAK mutational status (Verstovsek, S. et al., 47th Annu Meet Am Soc Clin Oncol (ASCO) (June 3-7, Chicago) 2011, Abst 6500).

The COMFORT-II trial compared ruxolitinib to best available therapy in 219 patients with primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF. This trial also met the primary endpoint, showing that 28.5% of patients treated with the study drug experienced a 35% or greater reduction in spleen volume at 48 weeks, compared with 0% of patients in the best available therapy arm (Harrison, C.N., 47th Annu Meet Am Soc Clin Oncol (ASCO) (June 3-7, Chicago) 2011, Abst LBA6501).

Incyte launched ruxolitinib phosphate (Jakafi™) in the U.S. shortly after approval. The product has orphan drug status in the U.S., Japan and the E.U. for the treatment of myelofibrosis.