Markov model

Inotersen

• It is uncertain whether vutrisiran provides a clinical benefit relative to patisiran or inotersen for hATTR-PN owing to uncertainty in the clinical evidence submitted by the sponsor. The CADTH clinical review concluded that the efficacy of vutrisiran is likely similar to patisiran (overall moderate certainty of evidence), while limitations in the sponsor-submitted NMA preclude meaningful conclusions from being drawn for the efficacy of vutrisiran vs. inotersen.
• The impact of AEs on the cost-effectiveness of vutrisiran was not adequately explored in the sponsor’s base case owing to the use of naive comparisons and the inclusion of only “treatment-related” AEs.
• The sponsor included in their model a benefit associated with SC administration vs. IV administration based on the assumption that less frequent and less invasive treatment will have a reduced negative impact on patients’ HRQoL. Approximately 98% of the incremental QALYs gained with vutrisiran relative to patisiran were owing to differences in administration route and frequency. The magnitude of any HRQoL benefit that patients may experience because of receiving treatment less frequently and by less invasive means is highly uncertain.
• The long-term efficacy of vutrisiran is uncertain owing to a lack of clinical data beyond 18 months. Potential waning of effectiveness was not explored.
• The survival benefit predicted for vutrisiran (incremental 0.07 and 3.26 LYs relative to patisiran and inotersen, respectively) is highly uncertain.
• The model structure, based on PND score, does not adequately reflect hATTR-PN, in that it does not capture autonomic symptoms associated with hATTR amyloidosis (e.g., pain, gastrointestinal symptoms). The validity, reliability, and responsiveness of PND scores to change have not been investigated in patients with hATTR-PN.

• Given the limitations identified within the sponsor’s economic analysis, CADTH was unable to provide a more reliable estimate of the cost-effectiveness of vutrisiran. Based on the sponsor’s analysis, vutrisiran is not a cost-effective treatment option for hATTR-PN at a willingness-to-pay threshold of $50,000 per QALY gained. The probability of vutrisiran being the optimal treatment was 0% in the sponsor’s analysis.
• There is insufficient clinical evidence to justify a price premium for vutrisiran over the currently available treatments for hATTR-PN. To ensure cost-effectiveness, vutrisiran should be no more costly than the lowest-cost funded treatment used for hATTR-PN.