Momelotinib Shows Strong Efficacy in JAK-Exposed Myelofibrosis Patients

Real-world outcomes of momelotinib (Ojjaara; GSK) in patients with myelofibrosis (MF) support the agent’s efficacy and capabilities in improving symptoms, reducing spleen size, increasing hemoglobin (Hb) levels, and reducing transfusion dependency in both Janus kinase (JAK) inhibitor-naïve and JAK inhibitor-exposed patients, which has been demonstrated in several clinical trials.

Red blood cells | Image Credit: © digitalpochi - stock.adobe.com

MF is a myeloproliferative neoplasm characterized by significant bone marrow scarring, extramedullary hematopoiesis, recurrent splenomegaly, and anemia due to its progressively decreased generation of red blood cells (RBCs). JAK inhibitors, such as ruxolitinib, are the first-line treatment for MF; however, resistance remains a key barrier for many patients. Additionally, ruxolitinib is highly associated with anemia or worsening of existing anemia, leading to the development of other novel JAK inhibitors, including momelotinib.¹

Momelotinib is an adenosine triphosphate-competitive small molecule JAK inhibitor that targets JAK1, JAK2, JAK3, and TYK2. On September 15, 2023, it received FDA approval for the treatment of patients with anemia and high/intermediate-risk MF, which includes the primary and secondary variants polycythemia vera or essential thrombocythemia. In multiple clinical trials, momelotinib has demonstrated superior benefits to other agents for MF, namely ruxolitinib (Jakafi; Incyte Corp). This was observed in the phase 3 SIMPLIFY trial (NCT01969838), where treatment with momelotinib yielded an increased therapeutic index of 50% to 83.3% from baseline to week 24, whereas ruxolitinib saw a decrease from 88.9% to 44.4%.^1,2

In the real-world, multi-center, retrospective MOMGEMFIN study, investigators assessed the safety and efficacy of momelotinib in adult patients with primary or secondary MF with anemia who were treated between March 2023 to July 2024. Anemia was defined as Hb values below 11g per dL for men and 10g per dL for women. Transfusion dependence was defined as needing 3 or more RBC units over a 12-week period or at least one unit per month. The evaluation of the spleen adhered to the 2013 ELN (IWG-MRT) standards.³

The patient cohort was primarily divided into 2 groups: JAK inhibitor-exposed patients (76.6%) and JAK inhibitor-naïve patients (23.4%). Among those previously treated with JAK inhibitors, ruxolitinib was the most commonly used (99%), with a median treatment duration of 16.8 months. Notably, 58.8% of these patients transitioned to momelotinib immediately or within a week after discontinuation of their previous therapy.³

In the JAK inhibitor-exposed group, the overall response rate (ORR) was 70.6% at 3 months and 85.7% at 6 months. In contrast, JAK inhibitor-naïve patients experienced a significantly lower ORR, at 16.6% at 3 months and 25% at 6 months. Additionally, the study considered patients based on their anemia status, particularly those who were transfusion-dependent. Among transfusion-dependent patients, the findings suggested that momelotinib not only improved Hb levels but also increased rates of transfusion independence.³

The study also highlighted treatment safety, with adverse events (AEs) such as thrombocytopenia reported in 10.3% of the patients, and most were grade 1 or 2.³

The findings from the MOMGEMFIN study support the potential of momelotinib as an effective treatment option for patients with MF with anemia, especially those with prior JAK inhibitor exposure. These critical real-world data deepen clinical understanding of momelotinib's role in managing MF in a diverse patient population with varying treatment histories.

REFERENCES

1. Momelotinib demonstrates efficacy, safety vs ruxolitinib for myelofibrosis in Japanese subpopulation analysis. Pharmacy Times. October 21, 2024. Accessed April 18, 2025. https://www.pharmacytimes.com/view/momelotinib-demonstrates-efficacy-safety-compared-with-ruxolitinib-for-treatment-of-myelofibrosis

2. Tefferi A, Pardanani A. Momelotinib for myelofibrosis: our 14 years of experience with 100 clinical trial patients and recent FDA approval. Blood Cancer J. March 18, 2024. doi:10.1038/s41408-024-01029-3

3. Perez-Lamas L, Diaz Adrian, Delgado R, et al. Real world outcomes of momelotinib in myelofibrosis patients with anemia: results from the MOMGEMFIN study. Blood Cancer Journal. April 17, 2025. doi:10.1038/s41408-025-01275-z