Sierra Oncology, Inc., a clinical stage drug development company focused on advancing targeted therapeutics for the treatment of patients with significant unmet needs in hematology and oncology, acquires the drug candidate momelotinib from Gilead Sciences. Momelotinib has been investigated in two completed Phase 3 trials for the treatment of myelofibrosis and has demonstrated a potentially differentiated therapeutic profile encompassing anemia-related benefits, as well as achieving substantive spleen and constitutional symptom control.
“The majority of myelofibrosis patients have anemia at diagnosis or develop it during treatment with other therapies, including ruxolitinib. Anemia is the most significant negative prognostic indicator in myelofibrosis patients and, as a result, one of the most important disease consequences to address,” says Dr. Srdan Verstovsek, medical oncologist and professor in the Department of Leukemia at The University of TexasMD Anderson Cancer Center, Houston, Texas. “The therapeutic focus in myelofibrosis has traditionally been on treating the enlarged spleen and constitutional symptoms common to the disease. However, optimal drug therapy would also address disease-related cytopenias, including anemia and transfusion dependency, while also improving splenomegaly and symptoms. The Phase 3 clinical data for momelotinib demonstrate clinical benefits in all of these categories and I believe the drug candidate warrants further development. Given its anemia benefit, momelotinib could potentially become an important option for the treatment of myelofibrosis.”
Sierra will pay Gilead a $3 million upfront fee for momelotinib and potential aggregate milestone payments of up to $195 million, which are largely associated with commercial sales of the drug. Sierra will also pay Gilead royalties on any sales of momelotinib, which will be tiered based on commercial success and range from mid-teens to high-twenties and will assume all currently ongoing clinical studies with momelotinib following a transition period.
“Unlike other JAK inhibitors, momelotinib addresses myelofibrosis-related anemia. The Phase 2 and Phase 3 data to date demonstrate that momelotinib consistently improves the anemia that frequently occurs in advanced myelofibrosis, postulated via ACVR1 inhibition. ACVR1 is a member of the TGF superfamily of receptors that regulate the iron metabolism pathway. ACVR1 activates the transcription of hepcidin, which leads to decreased erythropoiesis. Demonstrable splenic responses and constitutional symptom control have also been achieved with momelotinib, suggesting that the compound is able to address a spectrum of unmet medical needs in myelofibrosis,” notes Dr. Barbara Klencke, chief development officer for Sierra Oncology. “Momelotinib also has a well-defined, predictable safety profile, with more than 180 patients still remaining on active long-term therapy, some benefitting from treatment for more than seven years, reinforcing its potential durable efficacy and favorable long-term tolerability.”