Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Clinical trial evidence from the SIMPLIFY-1 and SIMPLIFY-2 studies indicates that momelotinib is likely to work as well as ruxolitinib for JAK inhibitor-naive patients and as well as best available therapy for JAK inhibitor-experienced patients. However, the non-inferiority margin in SIMPLIFY-1 was wider than typically accepted, and TSS results were not statistically significant, leading to a moderate benefit classification.
Cost effectiveness
The cost-effectiveness estimates for momelotinib are within the range that NICE considers acceptable for Healthcare resources, particularly for both JAK inhibitor-naive and experienced populations. The committee concluded that the costs of treatment with momelotinib are similar to those of ruxolitinib, supporting its cost-effectiveness.
Quality of life
The evidence suggests that momelotinib improves symptoms associated with myelofibrosis, particularly in terms of blood transfusion independence and total symptom score. While the exact HRQoL data is not detailed, the improvements in symptom management indicate a moderate positive impact on quality of life.
Supporting Domains
Safety and Adverse Effects
Momelotinib has an acceptable safety profile, with adverse events being manageable. The committee noted concerns regarding treatment discontinuation due to adverse events, but these were attributed to the study design rather than inherent safety issues.
Comparator Selection
The comparators used in the clinical trials were appropriate, with momelotinib being compared to ruxolitinib for JAK inhibitor-naive patients and best available therapy for JAK inhibitor-experienced patients. This selection aligns well with current treatment practices.
Patient Population and Subgroups
The trials included a representative population of patients with intermediate-2 or high-risk myelofibrosis and moderate to severe anaemia. However, there were some limitations in subgroup analyses, particularly regarding the definition of moderate to severe anaemia.
Care Pathway Integration
Momelotinib can be integrated into existing treatment pathways with minor adjustments. The committee noted that it would be a valuable addition to the treatment options available for myelofibrosis, particularly for patients who have not responded to ruxolitinib.
Resource Use and Cost Implications
The budget impact of momelotinib is manageable, with the committee concluding that its costs are similar to those of ruxolitinib. This suggests that the resource implications are justifiable given the expected benefits.
Evidence Quality and Robustness
The evidence base is supported by phase 3 trials (SIMPLIFY-1 and SIMPLIFY-2), although there are some concerns regarding the non-inferiority margins and the generalizability of results due to the exclusion of ESAs in the trials.
Uncertainty, Sensitivity, and Broader Impacts
While there are some uncertainties regarding the long-term outcomes and the impact of treatment discontinuation, the overall context is favorable, with a significant unmet need for effective treatments in myelofibrosis.
