GSK's Ojjaara (Momelotinib) Receives FDA Approval as First and Only Therapy for Myelofibrosis Patients with Anemia

On September 15, GSK announced that the FDA had approved Ojjaara (momelotinib) for marketing to treat intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis (polycythemia vera and essential thrombocythemia) in adult patients with anemia. Ojjaara is the first and only treatment option applicable to myelofibrosis patients with anemia.

Momelotinib is a novel drug with a differentiated mechanism of action that targets JAK1, JAK2, and ALK2. By inhibiting JAK1 and JAK2, it can improve systemic symptoms and splenomegaly. Unlike other JAK inhibitors, momelotinib can also inhibit ALK2. Excessive expression of hepcidin in myelofibrosis leads to anemia, and momelotinib can improve inflammatory anemia because it inhibits ALK2-mediated hepcidin expression in the liver, mobilizes intracellular iron into the bloodstream, thereby stimulating red blood cell production and subsequently improving myelofibrosis-related anemia.

Momelotinib was initially developed by Sierra Oncology and acquired by GSK for approximately $1.9 billion in July 2022, through the acquisition of the company.

This approval for marketing is based on the positive results of the pivotal Phase III MOMENTUM study and the subgroup of adult anemia patients from the Phase III SIMPLIFY-1 trial.

MOMENTUM Study is a randomized, double-blind global Phase III clinical trial designed to evaluate the safety and efficacy of momelotinib in treating and reducing key disease characteristics, including symptoms, transfusions (due to anemia), and splenomegaly. The trial enrolled 195 patients with symptoms, anemia, and prior treatment with a JAK inhibitor, who were randomly assigned in a 2:1 ratio to receive either momelotinib (n=130) or danazol (n=65).

The primary endpoint of the study was a ≥50% reduction in TSS from baseline during the 28 days prior to the end of Week 24, as assessed by the Myelofibrosis Symptom Assessment Form. Key secondary endpoints included the TI rate for ≥12 weeks prior to the end of Week 24, hemoglobin levels ≥8 g/dL, and the SRR for a ≥35% reduction in spleen volume from baseline at Week 24.

The results showed that the trial had met the primary endpoint and key secondary endpoints, including Total Symptom Score (TSS), Transfusion Independence (TI) rate, and Spleen Response Rate (SRR). Specifically, Momelotinib vs. control group: proportion of patients achieving TSS ≥50% was 25% vs. 9% (p=0.0095), transfusion independence: 31% vs. 20% (p=0.0064, non-inferiority), SRR ≥35%: 23% vs. 3% (p=0.0006).

Myelofibrosis is a rare blood cancer caused by dysregulated JAK signaling pathway and transcriptional activator signal transduction, with symptoms including systemic manifestations, significant splenomegaly, and progressive anemia. In the United States, myelofibrosis affects approximately 20,000 patients, of which about 40% are already anemic at diagnosis, and nearly all patients eventually develop anemia. Currently approved JAK inhibitors only address systemic symptoms and splenomegaly but have bone marrow suppressive effects, which can exacerbate anemia. Reducing the dose to mitigate this side effect significantly compromises treatment efficacy.

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