Pompe disease (PD) is a rare, progressive neuromuscular disease that severely affects motor and respiratory functions. Late onset PD (LOPD) is the most common phenotype. Current treatment involves enzyme replacement therapy (ERT) with alglucosidase alfa, which was first approved in 2006. In Europe, the treatment landscape is changing as two new ERTs have been filed for regulatory approval: avalglucosidase alfa and cipaglucosidase alfa plus miglustat. We analyzed how health technology assessment (HTA) and reimbursement criteria may be applied to ERTs in key countries for patients with PD.

Eighteen different factors were identified from the pivotal trials (LOTS, COMET, and PROPEL) for the three recombinant enzymes. These covered the categories of trial design, endpoints, quality of life, and other product characteristics. Twenty-six HTA experts and health economists from Denmark, England, France, Germany, Italy, the Netherlands, Spain, and Sweden with rare disease experience were interviewed during the period from July to September 2021. In structured discussions, each participant was asked to rate (from one to seven) the factors in terms of their importance and impact on the HTA evaluation and reimbursement of treatments for adults with PD.

The following factors were highly rated: a well-defined PD trial population; use of an active trial comparator; efficacy in both treatment naïve and experienced subpopulations; a superiority study design; and payer-relevant endpoints and quality of life improvements. The five lowest rated factors were open-label data, biomarkers, innovation, ease of administration, and mode of action. While the results were mostly consistent across countries, the HTA expert viewpoints varied depending on the country. For example, HTA experts in Italy, the Netherlands, and Sweden rated innovation and biomarkers more highly than German experts.

As new ERTs become licensed, achieving reimbursement and successful HTA of them will require a clear exposition of payer-relevant evidence for the LOPD population in the target country, including comparative randomized controlled trial data, benefits for experienced and treatment naïve subgroups, and payer-relevant endpoints and quality of life gains.