Lifecycle management of orphan drugs approved in Japan

Abstract Background: The development of orphan drugs (ODs) is challenging from both development and business perspectives because of their small patient populations. To overcome such business challenges, lifecycle management (LCM), which maximizes profits by increasing sales and extending product lifetimes, is important to overcome the business challenges arising from their small patient populations. To clarify the activities of the LCM of ODs, we investigated additional indications that contribute to market expansion and marketing exclusivity using the patent extension and re-examination system of ODs approved in Japan between 2004 and 2019.Results: The 203 ODs consisting of 173 active ingredients were approved in Japan between 2004 and 2019. Sixty-eight (39%) of the 173 active ingredients have additional indications, of which 57 have at least one non-OD indication. Three-fourths of the 203 ODs had patent rights, and most of them included substance or use claims. Although the re-examination period for most ODs was 10 years after the approval, most patents had a longer duration than the re-examination period. Conclusions: Pharmaceutical companies were actively adding non-OD indications and were emphasizing the use of patent rights by registering extensions of substance or use patents for exclusive marketing periods. These results indicate that LCM through the addition of indications and registration of patent extensions is carried out as a strategy for many ODs in Japan, similar to the LCM of general non-ODs.