Long-term durability in cost-effectiveness models of Gene therapies: Review of health technology assessment cases

Several in vivo gene therapies have gained market access in the US and Europe.

These gene therapies are designed to have a long-term effect after a single treatment. Several Health Technology Assessment (HTA) bodies have analyzed the cost-effectiveness of gene therapies over the long-term, despite the limited availability of clinical data. In cost-effectiveness models of in vivo gene therapies reviewed by HTA bodies, one of the key value drivers is the durability of the treatment effect over the long-term. Understanding how HTAs consider the translation of short-term clinical data into long-term treatment effects is critical to designing clinical trials & developing health economic models to meet their needs.
We endeavoured to systematically map how HTA bodies approached the translation of short-term clinical evidence into long-term treatment effects of in vivo gene therapies. We performed a series of HTA case reviews of in vivo gene therapies in North America and Europe.
HTAs of the gene therapies onasemnogene abeparvovec (spinal muscular atrophy) and voretigene neparvovec (inherited retinal disorders) were reviewed across four countries (US, Canada, UK, France). In all assessments, clinical trial data, long-term follow-up data, and pre-clinical data were used to support the long-term treatment durability. Available data for Onasemnogene abeparvovec, included 2-year trial data and up to 5.6 years of follow-up data. 3/4 HTAs accepted a lifetime treatment effect and 1/4 accepted an effect over the model horizon of 10-years (France). The available data on Voretigene neparvovec included a 2-year trial (1-year controlled) and up to 7.5 years of follow-up data. 3/4 HTAs accepted a 10-year treatment effect, which included a waning period of another 10 years by 2/3. One HTA (UK) accepted a 40-year treatment effect.
The acceptance of long-term treatment durability differed materially between HTAs in each case. However, at minimum, a 10-year treatment effect was accepted based on 2-year trial data, 5 years of follow-up data, and pre-clinical rationale. This has relevant implications for health economic modeling and pricing strategy of similar gene therapies.


Connor Buffel (1), Inês Oliveira (1), Geert Vander Stichele (1,2)


Integrated Strategic Market Access Services (ISMS) (1), GenBytes (2)

Presenting author

Inès Oliveira, Market Access and Health Economic Analyst, ISMS
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