Teprotumumab (Tepezza)

Key Messages

• Canada’s Drug Agency (CDA-AMC) recommends that Tepezza should not be reimbursed by public drug plans for the treatment of moderate to severe active thyroid eye disease (TED) in adult patients.
• Evidence from 3 randomized controlled trials (RCTs) in patients with moderate to severe active TED demonstrated that Tepezza improved proptosis and overall response at 24 weeks compared with placebo; however, vision outcomes, identified by patients and clinicians as a key treatment priority, were not assessed. Furthermore, the evidence regarding diplopia, another outcome of importance to patients and clinicians, had several limitations, including the use of subjective assessment methods, failure to meet multiplicity hierarchy testing, and uncertainty in the effect estimates due to wide confidence intervals (CIs).
• There was no direct comparative evidence evaluating the effectiveness of Tepezza versus any active treatment. The sponsor-submitted indirect evidence was insufficient to support a definitive conclusion about the comparative effects of Tepezza due to substantial limitations, including heterogeneity across included trials, reliance on unanchored matching-adjusted indirect comparisons (MAICs), failure to account for relevant effect modifiers, small effective sample sizes after matching, and considerable uncertainty in the effect estimates due to wide CIs. The indirect treatment comparison (ITC) evaluated Tepezza versus IV methylprednisolone (IVMP) only and did not include other relevant comparators such as rituximab, tocilizumab, and mycophenolate mofetil (MMF).
• The Canadian Drug Expert Committee (CDEC) acknowledged that moderate to severe active TED is a rare and serious condition associated with significant unmet clinical need. However, based on the evidence provided, the committee was unable to conclude that Tepezza addresses these unmet needs as effectively as, or more effectively than, existing off-label treatments. In addition, unlike current off-label drugs for this condition, evidence on the long-term effects of Tepezza remains limited.