OBJECTIVES: Many pharmaceutical treatments for severe, ultra-rare diseases have weight-based dosing regimens. When the indication covers both pediatric and adult patients, this can result in significant variation in drug utilization and costs per patient. For these high-cost treatments, this introduces additional complexity and uncertainty in price determination by payers. This analysis aims to understand how weight-based dosing impacts pricing and reimbursement outcomes across Germany, France, Italy and Spain.

METHODS: Treatments with marketing authorization from 2014 onwards were extracted from Orpha.net. Criteria for inclusion were: weight-based dosing; prevalence ≤10 per million; pediatric and adult indication; chronic treatment; first approved in indication. Drug prices and reimbursement outcomes were collected from the relevant health technology assessment (HTA) body website.

RESULTS: Overall, 7 drugs were identified. All 7 drugs were reimbursed in all EU4 markets, except for vestronidase alfa in France and elosulfase alfa, asfotase alfa, velmanase alfa and olipudase alfa in Spain where these treatments were not recommended for reimbursement. Annual list prices ranged from €321K per patient for velmanase alfa to €1.1 million for vestronidase alfa and were lowest in Germany (post-AMNOG) for 5 out 7 drugs. In Germany, all drugs had a list price reduction following the end of the pre-AMNOG free-pricing period (mean: 26.7%, min, max: 11.0%, 39.0%).

CONCLUSIONS: Although most treatments were reimbursed in all markets at a relatively high list price, it is likely that significant confidential discounts would have been required, as suggested by price reductions following negotiations in Germany. The high number of treatments not recommended for reimbursement in Spain suggests payer uncertainty due to high costs and weight-based dosing in this budget-focused market. It is important for payers and manufacturers to work together to manage the uncertainty of weight-based dosing to reach an agreement that satisfies all stakeholders and enables access for patients in need.