OBJECTIVES: Gene therapy involves replacement, addition, or other modifications of genes, offering the prospect of long-term or permanent cure for inherited genetic disorders. We aim to identify and review HTAs for gene therapies for heritable diseases in the US and key European markets.

METHODS: Searches for HTA evaluations of gene therapies for inherited disorders were conducted across ICER (USA; n=1), NICE (England; n=1), HAS (France; n=1), and G-BA (Germany; n=1).

RESULTS: ICER assessed voretigene neparvovec (VN; Spark Therapeutics) for RPE65-mediated retinal disease. It concluded that VN provided a small to substantial improvement over standard care, but was uncertain about long-term benefit, and noted that high drug costs of $850,000/patient made demonstrating cost-effectiveness difficult.

NICE recommended Strimvelis (GlaxoSmithKline) for treatment of adenosine deaminase severe combined immunodeficiency. The seriousness of the condition, improved outcomes and quality of life, and expected 5-year budget impact (BI) of £2.35 million were considered to outweigh risks associated with high drug costs (€594,000/patient) and uncertainties in clinical data.

Alipogene tiparvovec (AT; uniQure) was evaluated by HAS and G-BA for familial lipoprotein lipase deficiency. HAS did not recommend reimbursement, owing to concerns about safety and long-term efficacy. G-BA found the extent of benefit of AT was not quantifiable. Despite costing €1.32 million/patient, the expected BI was below the €50 million/year threshold for orphan technologies owing to the small patient population, and G-BA accepted AT. However, AT has since been withdrawn from European markets by the manufacturer due to limited use.

CONCLUSIONS: Uncertainty around clinical data from small populations and extremely high drug costs are key HTA challenges facing gene therapies, especially when cost-effectiveness must be demonstrated. However, their one-time use combined with potential long-term/lifetime benefits provides the opportunity to demonstrate value for money. As further high-cost gene therapies are commercialized, management of combined BI may become increasingly important.