Introduction <p>Orphan drugs have a special status within early benefit assessment (BA) in Germany, as they are only subject to limited assessment. A regular BA is performed if the annual sales threshold of €30 million is exceeded. We examined the development of prices and costs of orphan drugs that had undergone both assessment procedures. We also described factors that may influence prices and costs.</p> Methods <p>We extracted prices and annual treatment costs per patient at two points for each assessment procedure: at the time of the decision on added benefit and after a price change following the assessment. We calculated the percentage changes in prices and described the potential impact of the extent of added benefit and the target population size on the negotiated prices and costs.</p> Results <p>We identified 23 orphan drugs that had undergone both assessment procedures. We found 27 price reductions, 1 constant price and no price increases after limited assessments, and 18 price reductions, 2 constant prices and 3 price increases after regular BAs. On average, prices decreased in both procedures: -14.7% after limited assessments and a further -12.6% after regular BAs. Average annual treatment costs also decreased after both procedures. The extent of added benefit and the target population size had an inconsistent impact on prices and costs.</p> Conclusion <p>Limited assessments and regular BAs of orphan drugs both lead to price reductions in most cases. The extent of added benefit and the target population size can only partially explain the large heterogeneity of results.</p>