The evaluation of orphan drugs raises both positive and normative issues. Due to the rarity of the disease, higher drug costs and greater uncertainty on effectiveness often result in incremental cost-effectiveness ratios (ICER) far beyond the usually accepted thresholds for reimbursement. However, decision makers may need to consider other criteria to assess the social value of orphan drugs such as equity, the rule of rescue, and the perceived need in the community. Hereditary Angioedema (HAE) is a rare congenital deficiency resulting in recurrent attacks of angioedema in affected patients. These episodes cause extreme pain and distress, and may even be fatal when air pathways are involved. In Italy, icantibant or C1-Esterase-Inhibitors (C1-INH) are the indicated treatments for acute attacks. Although more expensive, icantibant may reduce time to symptom-relief and the need for further treatments. Nonetheless, evidence on its social value is missing. The present study aims at evaluating the cost-effectiveness of icantibant and providing new insights on other potentially relevant criteria for decision making on HAE treatments.

A cost-effectiveness model of icantibant versus C1-INH (Berinert) was developed. Using a two-part bayesian model, costs were estimated from real-world data of an unpublished national registry. Efficacy data were synthesized from both the registry and an indirect comparison of existing trials, whereas utilities were derived from the literature.

In our Italian registry, respectively 98 percent and 60 percent of patients self-administered icatibant or Berinert at home in absence of medical personnel. On average, per treatment costs were 60 percent higher and attack duration 25 percent shorter with icantibant compared to Berinert. The resulting ICER greatly exceeded the considered threshold of EUR30,000.

On cost-effectiveness grounds icantibant did not demonstrate good value for money compared to Berinert. However, further considerations are needed on whether standard health-related quality of life measures are able to truly reflect societal preferences for HAE treatments.The use of real-world data for the economic evaluation of orphan drugs can support decision making when evidence from clinical studies is too sparse.