Pompe disease (or glycogenosis type II) is a rare inheritable progressive muscle disease caused by a deficiency of the enzyme acid α-glucosidase and belongs to the glycogen and lysosomal storage disorders.

The disease is characterized by a continuous clinical spectrum of phenotypes. The progressive, classic-infantile form is at the severe end of the spectrum. Without disease specific treatment these patients die within the first year of life.

Pompe disease became the first treatable heritable muscle disorder when enzyme replacement therapy (ERT) with alglucosidase alfa was developed.

The late-onset form is at the least severe end of the spectrum, where the disease particularly affects skeletal muscle and respiratory function. However, even these patients eventually require a wheelchair and become ventilator dependent. Furthermore patients’ life expectancy and quality of life are reduced.

Pompe disease became the first treatable heritable muscle disorder when enzyme replacement therapy (ERT) with alglucosidase alfa was developed. Survival for classic-infantile patients improved hugely with ERT, with a survival rate of 72% at age 36 months. A model-based study estimated that ERT increases survival by more than 13 years.

In adult patients with Pompe disease, ERT has been shown to improve muscle strength, respiratory function and quality of life. Survival also improved significantly (hazard ratio of 0.41, after correction for age, gender, country of residence and disease severity). In our study, we estimate that ERT leads to survival gains of between 1.9 and 5.4 years in adult patients.

Treatment at a cost

Like other treatments for rare diseases, ERT for Pompe disease is very expensive, costing €450,000 annually per adult patient (average weight). Although price setting of drugs is not transparent, high prices of orphan drugs could be explained by various factors, including the need to recoup high R&D costs on a small number of patients; high manufacturing costs; lack of competition; and perceived high value of the product.

Our study examined the ratio of incremental costs and effects of ERT versus supportive treatment in adult patients with Pompe disease. It showed that despite substantial survival gains and improvements in quality of life, costs of generating one additional quality adjusted life year with ERT are between €1.8 million and €3.2 million, depending on the way survival was estimated.

This example outlines the difficult position policymakers are in when making reimbursement decisions on orphan drugs. On the one hand, the therapy of interest is very effective and no alternative treatments exist. Furthermore, from an ethical point of view it is difficult to deny patients an effective treatment which happens to be expensive because the targeted disease is rare.

The key questions are whether a societal preference for rarity exists and how much society wants to avoid denying access to treatment for patients with these diseases.

On the other hand, policymakers face a constrained budget. To raise the money for one drug either requires other treatments to be displaced or the taxes or health insurance premiums to be increased. But there is a limit to the latter as well. From an efficiency argument, money spent on orphan drugs could have led to more health gains in more cost-effective treatments (often for non-rare diseases).

The use of cost-effectiveness as a criterion in reimbursement decisions on orphan drugs has been a topic of much debate. However, even if cost-effectiveness is used other criteria also seem to play an important role in reimbursement decisions, including prevalence of the disease; disease severity; unmet medical need; and budget impact.

The key questions are whether a societal preference for rarity exists and how much society wants to avoid denying access to treatment for patients with these diseases. Various positive reimbursement decisions for orphan drugs and the existence of several government programmes, such as the Life Savings Drug Program in Australia and the Scottish Rare Conditions Medicines Fund, which are specifically designed to provide patients with rare diseases access to treatment, imply that policymakers believe a preference for rarity exists.

Empirical evidence on societal preferences for rarity is scarce and mixed. More research is needed on these societal preferences, and how policymakers incorporate these views in decision making. Meanwhile, policymakers can use cost-effectiveness studies as an instrument to engage in negotiations with drug manufacturers on prices of orphan drugs.