Controlled access to lumasiran in primary hyperoxaluria type 1: evaluation of a new access route for orphan drugs in the Netherlands

BACKGROUND AND HYPOTHESIS: In search for controlled access to expensive innovative orphan drugs, a national access route called 'Orphan Drug Access Protocol' (ODAP) was developed and piloted with lumasiran, a new drug for patients with primary hyperoxaluria type 1 (PH1). Here, we present a 2-year evaluation of this pilot study. METHODS: Specialists from the Dutch PH1 Expert Centre and the national ODAP steering group developed a protocol for controlled and conditional treatment of children and adults with PH1 with lumasiran. Indication for treatment is based on specific clinical characteristics. Cessation or continuation of therapy is evaluated every 6 months for 5 years by a national indication committee consisting of PH1 specialists, based on biochemical and clinical response. Drug wastage is minimized by centralizing and pooling patients for administration. RESULTS: Between September 2022 and September 2024, 21 PH1 patients were reviewed and 76% were deemed eligible for lumasiran treatment. Ten patients were already receiving lumasiran through clinical trials or early access programs at time of assessment. The follow-up time with lumasiran was 0.1-6.6 years, including trial years. All patients with >1 year lumasiran treatment responded significantly biochemically and clinically. Details on outcomes are presented. Denials for lumasiran therapy were nearly all based on full pyridoxine responsiveness. All denied patients, except one, had good clinical outcomes. This patient received lumasiran after initial denial based on clinical and biochemical course. Patient selection and minimizing wastage saved approximately €3 227 065 per year based on the official list price. CONCLUSIONS: This national ODAP protocol enabled access to lumasiran therapy for severely ill patients, prevented unnecessary treatment in others, and provided new insights into the real-world effectiveness of lumasiran in PH1 patients through systematic monitoring. It may serve as a template for future access routes to new expensive therapeutics in orphan diseases.