OBJECTIVES: Due to high unmet needs and low prevalence, orphan drugs can be approved by regulatory authorities based on evidence demonstrated through single-arm study designs; indeed, randomized studies in rare diseases may not be feasible. As part of a health technology assessment (HTA) evidence package, however, value demonstration through comparison to existing therapies or supportive care is always required. This study aimed to explore the value perceived by reimbursement authorities for an orphan therapy in a single-arm trial evidence package, and to understand any supplementary evidence requirements for value demonstration. METHODS: Fourteen experts in HTA, pricing and reimbursement (P&R) decision-makers, and influencers in China, South Korea, Taiwan, and Thailand were recruited and interviewed, following a comprehensive discussion guide. The responses were further analysed to identify the key challenges in value demonstration and what clinical and economic evidence the respondents found acceptable in evaluating orphan drugs. RESULTS: In all countries, payers valued innovative therapies for rare diseases and were understanding towards limitations in study design and the availability of evidence for value demonstration. Systematic reviews and retrospective database studies investigating the efficacy and safety of existing therapies or supportive care, which allow for qualitative comparisons against the new therapy, were generally expected by most of the respondents. Cost-effectiveness analysis was required in some of the countries, with the rest expecting only a budget-impact analysis based on local epidemiological data. Findings were similar for therapies for diseases with low prevalence but without orphan drug designation. CONCLUSIONS: Unmet needs in rare diseases are high, and effective new therapies are welcomed and valued by payers in these key reimbursed markets in Asia. Decision makers are willing to show a degree of flexibility in their evidence requirements for these kinds of products.