OBJECTIVES: Drugs for rare diseases may receive additional support or incentives during pricing and reimbursement. Some countries adapt their health technology assessment (HTA) processes for orphan and ultra-orphan drugs. We analysed HTA outcomes to understand the impact of these adaptions on decision-making.

METHODS: HTAs published in 2023 in 13 countries across Europe, North America, and the Asia-Pacific were reviewed, with data extracted regarding appraisal type and decision. Based on disease prevalence, appraisals were categorised as non-orphan, orphan, or ultra-orphan. Decisions were analysed to evaluate the likelihood of HTA success according to the presence of adapted or separate processes for orphan or ultra-orphan drugs.

RESULTS: 896 submissions were included in the analysis: non-orphan (n=722), orphan (n=134), and ultra-orphan drugs (n=40). Across all markets, HTA success was slightly lower for orphan and ultra-orphan drugs (both 75%) compared to non-orphan drugs (82%). Markets that had separate ultra-orphan pathways or considered orphan status had higher positive recommendation rates than those that did not consider orphan status (88%, 82%, and 64%, respectively).

Orphan drugs were more likely to be recommended in markets with considerations (83%) than in those without (60%). The likelihood of recommendation of ultra-orphan drugs was higher in markets with a separate appraisal process for highly specialised drugs (90%) compared to markets that considered rarity as part of their normal appraisal process (77%) or did not consider rarity at all (65%). This trend also applied to non-orphan drugs: 89% were recommended in markets with considerations and 82% in markets with separate processes versus 65% in those without either.

CONCLUSIONS: Drugs treating lower-prevalence diseases had a reduced rate of HTA success. However, recommendations were more likely in markets with modified or separate HTA processes based (in part) on rarity. Interestingly, markets with modified or separate HTA processes saw higher HTA success across all drugs, including non-orphan.