CADTH made the following changes to the sponsor’s economic model to account for identified limitations: removed the assumption of Myasthenia Gravis Activities of Daily Living (MG-ADL) score deterioration over time on standard of care (SOC); reduced the mortality rate from myasthenic crisis; reduced the frequency of routine clinician visits; assumed all vaccination and administration costs would be covered by the public payer; and assigned correct probabilistic distributions to the model inputs. CADTH’s reanalyses resulted in the same findings as the sponsor: adding eculizumab to SOC compared to SOC alone is not cost-effective at conventionally accepted incremental cost-effectiveness ratio (ICER) thresholds. Based on CADTH reanalysis, eculizumab plus SOC compared to SOC alone is associated with an ICER of $1,505,712 per quality-adjusted life-year (QALY) gained and has a 0% probability of being cost-effective for patients with refractory AChR-antibody–positive generalized myasthenia gravis (gMG) at a willingness-to-pay (WTP) threshold of $50,000 per QALY. A price reduction of 91% would be required to achieve an ICER below a WTP threshold $50,000 per QALY. The submitted price of eculizumab is the key driver of the cost-effectiveness estimates. Important limitations remain that CADTH was unable to address, including assumptions made about the natural history of gMG and the anticipated use of eculizumab. Together, these introduce structural and parameter uncertainties that affect the overall precision of the cost-effectiveness estimates. The majority of incremental QALYs (> 90%) occurred beyond the observation period of the clinical trial and its extension study; as extrapolations were made based on several assumptions with high levels of uncertainty, the magnitude of this QALY gain is also uncertain. These limitations affected CADTH’s ability to conduct a precise health economic analysis. Despite the limitations noted above, it is very unlikely that eculizumab would be considered cost-effective without considerable price reduction.