Aaron T. Gerds, MD, MS, discusses the clinical trial development of momelotinib, a JAK1/JAK2 inhibitor that is being investigated for the treatment of patients with myelofibrosis.
Aaron T. Gerds, MD, MS, assistant professor in Medicine (Hematology and Medical Oncology) at the Cleveland Clinic, discusses the clinical trial development of momelotinib, a JAK1/JAK2 inhibitor that is being investigated for the treatment of patients with myelofibrosis.
Early in it course of development, momelotinib showed promising efficacy in the SIMPLIFY-1 (NCT01969838) and SIMPLIFY-2 (NCT02101268) studies. Momelotinib was initially intended to address enlarged spleens and symptom burden in patients with myelofibrosis. Across the studies of momelotinib, investigators also found that improve cases of anemia.
In the phase 3 MOMENTUM study (NCT04173494), momelotinib was compared with danazol in patients with myelofibrosis previously treated with a JAK inhibitor and who are symptomatic and anemic. Results for from MOMENTUM were recently presented during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.
0:08 | So, the MOMENTUM study is an important study in the development of momelotinib for the treatment of myelofibrosis. There have been other randomized phase 3 trials, the SIMPLIFY-1 and 2 trials, as well as a phase 2 scientific study that have been all completed. And again, MOMENTUM really represents the last stage in this drug development with an eye towards regulatory approval.
0:34 | So early on, momelotinib was being developed as another JAK 1/2 inhibitor, with the goal of treating enlarged spleens and symptom burden in patients with myelofibrosis. Over the early phases of development, though, it was also noticed that patients treated with momelotinib have often had improvements in their anemia. And of course, anemia is a big problem in myelofibrosis. It's one of the diagnostic criteria for diagnosing myelofibrosis as well as it's very common and leads to significant reductions in quality of life and requires some time transfusions, which are course are intensive. And lastly, anemia is associated with a worse survival in patients with myelofibrosis. It represents a massive unmet need.
1:23 | Current JAK inhibitors that are approved for the treatment of myelofibrosis do not necessarily improve anemia and often make anemia worse as a side effect. So again, all the more reason to explore this agent that could potentially improve anemia. And really, that was like the main focus of the MOMENTUM study. So, it included patients with myelofibrosis who are symptomatic and had splenomegaly but were also anemic. Many of which were transfusion dependent coming in on study. And the key endpoints included freedom from transfusions as well as transfusion independence rate. The comparator arm was danazol and danazol was selected because it is often used to treat anemia and patients with myelofibrosis as recommended by both the NCCN and ESMO guidelines.