Incyte has announced results from two ongoing clinical trials of Jakafi ( Ruxolitinib ), an oral JAK1 and JAK2 inhibitor that is FDA-approved for the treatment of patients with intermediate or high-risk myelofibrosis, that were presented at the 18th Congress of the European Hematology Association ( EHA ) in Stockholm, Sweden.

In a three-year follow-up analysis of the Phase III COMFORT-II study, treatment with Jakafi was associated with improved overall survival and sustained reductions in spleen size compared to best available therapy.
In a separate exploratory analysis of bone marrow fibrosis data from an ongoing Phase I/II single-arm, open-label clinical trial, by 48 months of treatment, Jakafi stabilized or reversed fibrosis of the bone marrow in 56% and 22%, respectively, of patients with myelofibrosis, a magnitude of an effect not seen historically with best available therapy.

Long-term outcomes from a Phase III study comparing Ruxolitinib with best available therapy for the treatment of myelofibrosis: a 3-year update of COMFORT-II

In a three-year follow-up analysis of the COMFORT-II study, an overall survival advantage was observed in patients treated with Jakafi compared to patients receiving best available therapy. A 52% reduction in risk of death was observed in the Jakafi arm compared with best available therapy ( hazard ratio, HR=0.48; 95% CI, 0.28-0.85; p=0.009 ), and the estimated probability of overall survival was significantly greater with Jakafi compared to best available therapy ( 81% compared to 61%, respectively ) at 144 weeks. Additionally, 51.4% of patients treated with Jakafi achieved a greater than or equal to 35% reduction from baseline in spleen size over the course of the study. Spleen response was maintained, with the median duration of this response not yet reached in the study.

Anemia and thrombocytopenia were the most common adverse events over the three-year follow-up; however, the rates of these events decreased over time. Among patients randomized to Jakafi and included in the extension phase, the general frequency of the most common non-hematologic adverse events ( peripheral edema, diarrhea and asthenia ) did not change over time.

The results are consistent with previous COMFORT-II and COMFORT-I study analyses, which demonstrated that Jakafi provides significant clinical benefits over best available therapy and placebo for patients suffering from intermediate or high-risk myelofibrosis.

Long-term intervention effects on bone marrow morphology in myelofibrosis: patients treated with Ruxolitinib and best available therapy

Data were presented from an exploratory analysis that evaluated long-term data of patients with myelofibrosis who were treated with Jakafi ( n=68 ) in a Phase I/II trial.
Biopsies were obtained at baseline and at 24 ( n=68 ) and 48 ( n=18 ) months, and bone marrow fibrosis grade was determined by three expert hematopathologists using the World Health Organization ( WHO ) scoring system and blinded to patient data and outcome.
Stabilization or improvement of bone marrow fibrosis was observed at both time points, and by month 48, bone marrow fibrosis was stabilized in 56% of Ruxolitinib-treated patients and improved in 22%.
The percentage of Ruxolitinib-treated patients with bone marrow fibrosis grade worsening at 24 and 48 months was 37% and 25%, respectively.
Separate samples were also collected from a multicenter observational database from three European Union countries ( 160 biopsies in a cohort of 139 patients ) in patients treated with best available therapy at 24 months ( n=97 ) and 48 months ( n=63 ).
Myelofibrosis is a life-threatening blood cancer that belongs to a group of diseases referred to as myeloproliferative neoplasms ( or MPNs ).
Myelofibrosis has a poor prognosis and limited treatment options. While the exact prevalence of myelofibrosis is uncertain, and estimates vary widely, based on extensive market research. Incyte estimates myelofibrosis affects about 16,000 to 18,500 people in the U.S.
The enlarged spleen and debilitating symptoms of myelofibrosis are linked to dysregulated signaling in the Janus kinase ( JAK ) pathway. This dysregulation may be caused by various mechanisms and mutations, such as the JAK2 V617F mutation.
Although allogeneic stem cell transplantation may cure myelofibrosis, the procedure is associated with significant morbidity and transplant-related mortality and is available to less the 5% of patients who are young and fit enough to undergo the procedure. ( Xagena )

Source: Incyte, 2013

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