Momelotinib, a new oral medication, received approval from the U.S. Food and Drug Administration (FDA) on September 15, 2023. This development marks a significant advancement in treating a specific blood cancer. The approval provides a new option for patients who previously had limited choices. This medication addresses multiple aspects of the condition, offering a comprehensive approach to patient care.
Addressing Myelofibrosis
Myelofibrosis is a rare type of bone marrow cancer that affects approximately 25,000 adults in the United States. This condition causes the bone marrow, which normally produces blood cells, to become scarred and fibrous. The scarring disrupts normal blood cell production, leading to various challenging symptoms.
Patients often experience an enlarged spleen, a condition known as splenomegaly, due to the body attempting to produce blood cells in other organs. Other common symptoms include fatigue, night sweats, bone pain, and unintended weight loss. A particularly debilitating symptom is anemia, a decrease in red blood cells, which affects about 40% of patients at diagnosis and almost all patients over time. Anemia significantly impacts a patient’s quality of life and can shorten survival, often requiring frequent blood transfusions. Existing treatments for myelofibrosis, while addressing some symptoms, frequently worsen anemia, leaving a notable gap in patient care.
Momelotinib’s Unique Approach
Momelotinib is classified as a Janus kinase (JAK) inhibitor, specifically targeting JAK1 and JAK2 pathways. These pathways are involved in the signaling of various cytokines and growth factors important for blood cell formation and immune function. By inhibiting these kinases, momelotinib helps to reduce spleen size and alleviate systemic symptoms.
Momelotinib also inhibits activin A receptor type 1 (ACVR1), also known as activin receptor-like kinase 2 (ALK2). This dual mechanism of action is particularly beneficial for addressing anemia in myelofibrosis patients. ACVR1 plays a role in regulating hepcidin, a hormone that controls iron levels in the body. By inhibiting ACVR1, momelotinib can lower hepcidin levels, which in turn increases iron availability for red blood cell production, thereby improving anemia. This distinct dual action differentiates it from other JAK inhibitors, which may not improve anemia and can even worsen it.
The Path to FDA Approval
The FDA approval of momelotinib on September 15, 2023, was supported by data from several clinical trials. The MOMENTUM study evaluated momelotinib against danazol, an androgen used to manage myelofibrosis-associated anemia. This international, double-blind, randomized phase 3 trial enrolled 195 patients with myelofibrosis who had previously received a JAK inhibitor and were experiencing anemia and symptoms. The MOMENTUM trial met its primary and secondary endpoints, demonstrating significant improvements in total symptom score, spleen volume reduction, and anemia, including increased transfusion independence.
Specifically, 25% of patients on momelotinib achieved a 50% or greater reduction in total symptom score at week 24, compared to 9% on danazol. Furthermore, 31% of patients treated with momelotinib achieved transfusion independence at week 24, versus 20% with danazol.
Supporting data also came from a subgroup of adults with anemia from the SIMPLIFY-1 and SIMPLIFY-2 phase 3 trials. The SIMPLIFY-1 trial compared momelotinib to ruxolitinib in JAK inhibitor-naive patients, showing comparable spleen response and a benefit in terms of anemia, including higher rates of transfusion independence. The SIMPLIFY-2 trial evaluated momelotinib against best available therapy (primarily continued ruxolitinib) in patients who had suboptimal responses or toxicities to prior ruxolitinib treatment. In this trial, momelotinib demonstrated improved spleen volume reduction, symptom response, and transfusion independence rates compared to the control arm.
The approval of momelotinib for adults with intermediate- or high-risk myelofibrosis, including those with anemia, provides a treatment option. It addresses both the underlying disease manifestations and anemia, benefiting patients and the medical community.