Incyte Corporation (Nasdaq: INCY) announced results of an interim analysis from a 12-week open-label, dose-escalation Phase II clinical trial involving more than 85 patients with intermediate or high-risk myelofibrosis (MF) for its proprietary oral JAK1 inhibitor, INCB39110. These results were presented today at the 2013 American Society of Hematology (ASH) Annual Meeting in New Orleans.
In this preliminary analysis of an ongoing Phase II trial that involved three doses (100 mg twice daily, 200 mg twice daily and 600 mg once daily), treatment with INCB39110 at doses of 200 mg twice daily and 600 mg once daily provided meaningful improvements in MF-related symptoms, including symptoms associated with splenomegaly. At week 12, 22.2 percent, 34.9 percent, and 50.0 percent of patients in the 100 mg twice daily, 200 mg twice daily, and 600 mg once daily dose groups, respectively, achieved at least a 50 percent improvement from baseline in their total symptom score (the primary endpoint); median percentage improvements from baseline at this time point were 28.5 percent, 45.8 percent, and 76.8 percent, respectively, across dose groups. Reductions in spleen volume were modest, with median percentage changes from baseline to week 12 of 5.0 percent, -14.1 percent, and -9.9 percent, respectively, across dose groups. The most common hematologic adverse events, regardless of causality, were anemia and thrombocytopenia, and the most common non-hematologic adverse events were fatigue, constipation and nausea. In comparison to JAK1/JAK2 inhibitors and JAK2 inhibitors, the findings from this analysis suggest that JAK1 inhibition may result in less myelosuppression. In patients not receiving post-baseline transfusions, mean hemoglobin levels in each dose group increased by week 2 and remained approximately 0.5 to 1.0 g/dL above baseline through week 12.
To access the presentation: ASH 2013 - Mascarenhas
“With the interim analysis of this trial combined with data from two other proof-of-concept trials in rheumatoid arthritis and psoriasis, we have a better understanding of JAK1 as a disease target, and we’re using this knowledge to focus the development of our broad portfolio of JAK1 inhibitors,” stated Richard S. Levy, M.D., Incyte’s Executive Vice President and Chief Drug Development and Medical Officer. “We are taking INCB39110, our most advanced JAK1 inhibitor, forward initially in solid tumors, starting with combinations that may not be as well-tolerated with a JAK1/JAK2 inhibitor as a result of the potential myelosuppressive effect of JAK2 inhibition.”