Population Pharmacokinetics and Exposure‑Response Analyses of Momelotinib, Its Active Metabolite (M21), and Total Active Moiety in Myelofibrosis

Rákkutatás · Myelofibrosis

Exposure to the total active moiety at 200mg once daily is associated with greater spleen volume reduction and higher odds of transfusion independence.

Momelotinib is a JAK1/2/activin A receptor type 1 inhibitor approved for the treatment of myelofibrosis with anemia. Population pharmacokinetic and exposure‑response analyses based on phase II/III trials showed that exposure to the total active moiety (TAM) at 200 mg once daily is associated with greater spleen volume reduction and higher odds of transfusion independence, but no significant relationship with symptom improvement. Higher TAM exposure was also associated with lower odds of grade 3/4 anemia and higher odds of peripheral neuropathy, while thrombocytopenia and diarrhea were not related to exposure.

Understanding the exposure–response profile of momelotinib informs dose selection and predicts tolerability for patients with myelofibrosis.

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