FDA Approves GSK’s First-in-Class JAK Inhibitor Ojjaara (momelotinib) for Myelofibrosis Patients with Anemia

▎Edited by the WuXi AppTec content team

Just now, GSK announced that the US FDA has approved its JAK inhibitor Ojjaara (momelotinib) for the treatment of adult anemia patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis (post-polycythemia vera and post-essential thrombocythemia).According to the press release, Ojjaara is the first approved drug for newly diagnosed and previously treated patients with myelofibrosis suffering from anemia, alleviating key symptoms of the disease such as anemia and splenomegaly.

Myelofibrosis isA rare blood cancer caused by dysregulation of JAK-STAT signalingCharacterized by systemic symptoms, splenomegaly, and progressive anemia. Previous studies have shown that about half of patients with myelofibrosis have moderate to severe anemia when they meet the criteria for JAK inhibitor treatment. However, currently approved JAK inhibitors can only improve symptoms and splenomegaly but may cause myelosuppression, potentially worsening anemia, leading to dose reduction and thus decreasing treatment efficacy.

Ojjaara has a unique mechanism of action, inhibiting three key signaling pathways: Activin A Receptor Type I (ACVR1), JAK1, and JAK2.Sierra Oncology submitted a New Drug Application (NDA) to the U.S. FDA for the drug's treatment of myelofibrosis in June of last year. In July of last year, GSK announced the completion of its acquisition of Sierra Oncology, obtaining the development rights to this investigational therapy.

This FDA approval in the U.S. was primarily based on data from the pivotal Phase 3 clinical trial MOMENTUM and data from a subgroup of adult anemia patients in the SIMPLIFY-1 Phase 3 clinical trial. The MOMENTUM trial aimed to evaluate the efficacy and safety of Ojjaara compared to danazol in myelofibrosis patients who were previously treated with JAK inhibitors, had anemia, and exhibited clinical symptoms. Analysis showed,Ojjaara Achieves All Primary and Key Secondary Endpoints. At 24 weeks of treatment, the proportion of patients in the Ojjaara group who achieved more than a 50% improvement in Total Symptom Score (TSS) from baseline was 25%, compared to 9% in the control group.Proportion of patients not dependent on transfusions at 24 weeks: 31% in the Ojjaara group vs. 20% in the control group; Proportion of patients with spleen volume reduction over 35%: 23% in the Ojjaara group vs. 3% in the control group. This indicates that Ojjaara shows statistically significant improvements over the control group in alleviating symptoms, spleen response, and controlling anemia, and these improvements are clinically valuable.

In these clinical trials, the most common adverse reactions were thrombocytopenia, bleeding, bacterial infection, fatigue, dizziness, diarrhea, and nausea.