From the Guidelines
Momelotinib is a JAK1/2 inhibitor used to treat myelofibrosis, a rare bone marrow cancer, with a typical dosage of 200 mg taken orally once daily. According to the most recent study 1, momelotinib may produce significant anemia responses, in addition to spleen and symptom responses, among patients with myelofibrosis. The study suggests that momelotinib inhibits ALK2-mediated expression of hepcidin in the liver, resulting in increased release of iron from sequestrated cellular stores and enhanced erythropoiesis.
Some key points to consider when using momelotinib include:
- It is specifically approved for adult patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis
- The typical dosage is 200 mg taken orally once daily, and it can be taken with or without food
- Treatment is usually continued until disease progression or unacceptable toxicity occurs
- Momelotinib works by inhibiting Janus kinase (JAK) 1, JAK2, and ACVR1 proteins, which are involved in signaling pathways that contribute to myelofibrosis symptoms and progression
- Patients should be aware of potential side effects, including diarrhea, thrombocytopenia, and increased liver enzymes, and regular blood tests are typically required to monitor blood counts and liver function during treatment
It's also important to note that momelotinib may interact with certain drugs, so patients should inform their healthcare provider of all medications they are taking. Additionally, peripheral neuropathy is an important side effect of momelotinib, and patients should be monitored for this condition during treatment 1.
From the FDA Drug Label
Momelotinib is an inhibitor of wild type Janus Kinase 1 and 2 (JAK1/JAK2) and mutant JAK2V617F, which contribute to signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function.
Momelotinib is a JAK inhibitor that targets JAK1, JAK2, and mutant JAK2V617F, playing a role in signaling pathways involved in hematopoiesis and immune function 2.
From the Research
Definition and Mechanism of Action
- Momelotinib is a novel JAK1/JAK2/activin A receptor type 1 (ACVR1) inhibitor 3
- It works by suppressing the hyperactive JAK-STAT pathway, addressing splenomegaly and symptoms associated with myelofibrosis 3
- Additionally, momelotinib improves anemia and reduces transfusion dependency through ACVR1 inhibition, which decreases hepcidin production and leads to improved erythropoiesis 3, 4
Clinical Trials and Efficacy
- Clinical trial data indicate that momelotinib is not inferior to ruxolitinib in spleen response and symptoms response, with improvement in anemia 5
- Momelotinib has been shown to provide additional benefit in alleviating transfusion-dependent anemia in myelofibrosis patients 4
- The recommended dose of momelotinib is 200 mg orally once daily, established after review of safety, efficacy, pharmacokinetic, and pharmacodynamic data 3
Safety Profile
- The most common nonhematologic treatment-emergent adverse event occurring in ≥20% of patients is diarrhea (any grade, 27% and grade ≥3%) 6
- Any-grade thrombocytopenia, anemia, and neutropenia occurred in 25%, 23%, and 7% of patients, respectively 6
- The incidence of adverse events of clinical importance (e.g., infections, malignant transformation, peripheral neuropathy, and hemorrhage) did not increase over time 6