Sierra Oncology has initiated a Phase III clinical trial to assess its investigational JAK1, JAK2 and ACVR1 inhibitor, momelotinib, for the treatment of myelofibrosis.
Inhibition of JAK1, JAK2 and ACVR1 decreases hepcidin and inflammation, restores iron homeostasis and red blood cells production. The mechanism is said to mitigate anaemia and transfusion dependency, both of which are characteristics of myelofibrosis.
The randomised, double-blind Phase III MOMENTUM trial will investigate the drug in 180 patients who are symptomatic, anaemic and received prior treatment with a JAK inhibitor.
Momelotinib will be compared to danazol, which is used to ameliorate anaemia in patients with myelofibrosis.
The study aims to validate the efficacy of Sierra Oncology’s drug on myelofibrosis symptoms, transfusion independence and splenomegaly.
The primary endpoint is the total symptom score (TSS) response rate at week 24.
Additional outcome measures include Transfusion Independence (TI) rate and splenic response rate (SRR) at week 24, TSS response duration to week 48 and patient-reported fatigue and physical function, among others.
Sierra Oncology chief development officer Dr Barbara Klencke said: “MOMENTUM is designed to confirm the array of benefits observed in prior Phase III studies, where momelotinib demonstrated a unique ability to improve anaemia and reduce transfusion dependency in patients with myelofibrosis, while also providing clinically comparable benefits on constitutional symptoms and enlarged spleens to other JAK inhibitors.”
The company intends to activate global trial sites in the near future. Top-line results from the trial are expected to be reported in the fourth quarter of 2021.
Sierra added that the company received the capital required to bring momelotinib towards potential commercialisation.
The company also revised its asset purchase agreement for the drug with Gilead Sciences . The new terms will see Gilead become a stockholder in Sierra.
In return, there will be a decrease in annual royalties to be paid by Sierra to Gilead upon commercialisation of the drug.