OBJECTIVES: Health Technology assessment (HTA) in ultra-orphan indications can be very challenging. The Scottish Medicines Consortium (SMC) has a new (April 2019) pathway for ultra-orphan medicines allowing them to be made available for three years while additional evidence is collected/generated prior to a final SMC assessment and reimbursement recommendation. This research systematically evaluates all therapies included under this new pathway and compares outcomes to other European HTA agencies.

METHODS: Medicines included under the new ultra-orphan pathway were identified from https://www.scottishmedicines.org.uk/ (to 24-Dec-2020). HTA reports by NICE, GBA, HAS, and NCPE for the same therapies were also identified and key information extracted.

RESULTS: Four therapies have been made available within the new ultra-orphan SMC pathway: Waylivra (Nov-2020), Brineura (Oct-2020), Luxturna (Feb 2020). Crysvita (Feb-2020) an average of 24.3 months post-European Commission approval (range:18.3-40.5 months). NICE recommended all four under the Highly Specialized Technologies pathway, all at earlier timepoints (mean 7.8 months). By contrast, the NCPE did not recommend any of the four. The G-BA deemed all four offered additional benefit although for three, a non-quantifiable benefit was proved because of orphan drug designation. HAS granted two an ASMR IV with the others ASMR II and III.

CONCLUSIONS: Four drugs have been made available under the new SMC ultra-orphan pathway to date. These have all been approved more rapidly by a cost-effectiveness-driven HTA with a specialized very rare disease pathway (NICE) but all been rejected by another cost-effectiveness-driven HTA without such a specialized pathway (NCPE). Clinical-benefit driven HTA bodies (HAS and GBA) also issued generally favorable outcomes. While the focus of most HTA bodies currently remains on evidence at submission, post-launch data collection is becoming an increasingly important access requirement in some markets, and this need for real-world evidence will likely further increase in the future.