Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Fremanezumab demonstrated a clear clinical advantage over best supportive care in both episodic and chronic migraine, with significant reductions in monthly migraine days. The evidence from the FOCUS trial indicates that more patients experienced a clinically meaningful reduction in migraine days compared to placebo. However, the uncertainty regarding its comparative effectiveness against botulinum toxin type A limits the rating to A+.
Cost effectiveness
The cost-effectiveness estimates for fremanezumab were below the acceptable threshold of £20,000 per QALY gained for both episodic and chronic migraine after three preventive treatments have failed. The committee concluded that fremanezumab is a cost-effective use of Healthcare resources, particularly for episodic migraine, which supports a rating of A+.
Quality of life
The use of the Migraine-Specific Quality of Life Questionnaire (MSQ) indicated moderate improvements in quality of life for patients treated with fremanezumab compared to placebo. While the committee acknowledged that the EQ-5D-5L was less sensitive to changes in quality of life due to migraine, the MSQ results support a positive impact on HRQoL, justifying a rating of A.
Supporting Domains
Safety and Adverse Effects
Fremanezumab has an acceptable safety profile, with adverse events primarily being mild to moderate. The committee noted that while there were some concerns regarding discontinuation rates, the overall safety data were manageable and comparable to existing therapies, justifying a rating of A.
Comparator Selection
The clinical trials compared fremanezumab against appropriate comparators, including placebo and botulinum toxin type A. The committee recognized that best supportive care was a relevant comparator for episodic migraine, which supports a strong rating of A+.
Patient Population and Subgroups
The FOCUS trial population was generally representative of the intended patient population, although some exclusions may limit generalizability. The committee concluded that the population studied was relevant, supporting a rating of A.
Care Pathway Integration
Fremanezumab can be integrated into existing care pathways with minor adjustments, as it is administered via subcutaneous injection. The committee noted that while some patients may require assistance with administration, the overall integration into clinical practice is manageable, justifying a rating of A+.
Resource Use and Cost Implications
The economic model indicated that fremanezumab has a manageable budget impact, with costs aligned with the expected benefits. The committee concluded that the resource implications were justifiable, supporting a rating of A.
Evidence Quality and Robustness
The evidence base for fremanezumab includes multiple randomized controlled trials, although some limitations in the generalizability of the FOCUS trial were noted. The overall quality of evidence supports a rating of A.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding the long-term effectiveness of fremanezumab and its comparative effectiveness against botulinum toxin type A. The committee acknowledged these uncertainties, which justifies a rating of B++.
