OBJECTIVES: Health Technology assessment (HTA) in ultra-orphan indications can be very challenging. Since April 2019, the Scottish Medicines Consortium (SMC) has a new framework for ultra-orphan medicines allowing them to be prescribed and reimbursed for three years while additional evidence is generated pending a final SMC assessment. This research systematically evaluates all therapies included under this new pathway and compares outcomes to other HTA agencies.

METHODS: Medicines included under the new ultra-orphan pathway were identified from https://www.scottishmedicines.org.uk/ (to 16-May-2022) and compared with respective HTA reports by NICE, GBA, HAS, and NCPE.

RESULTS: Eight therapies have been made available under the new ultra-orphan SMC pathway an average of 30.2 months post-European Commission approval (range:18.3-90.7 months). 5/8 represented their first assessment but 3/8 had previously been not recommended/restricted by SMC. NICE recommended 6/8 under the Highly Specialized Technologies pathway, all at earlier timepoints (mean 12.3 months), with one restricted (STA) and another HST ongoing. By contrast, the NCPE did not recommend any of the six it had assessed. The G-BA deemed all eight offered additional benefit although for 4, a non-quantifiable benefit was proven because of orphan drug designation. HAS granted four an ASMR IV, three ASMR III and one ASMR II

CONCLUSIONS: Eight medicines have been made available under this new SMC ultra-orphan pathway. These have almost 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.