Assessing the potential clinical impact of reciprocal drug approval legislation on access to novel therapeutics in the USA: a cohort study

Objective To quantify the potential effect of reciprocal approval legislation on access to clinically impactful therapeutics in the USA. Design A cohort study. Setting New therapeutics approved by the Food and Drug Administration (FDA), European Medicines Agency (EMA) and/or Health Canada between 2000 and 2010. Main outcome measures Characteristics of new therapeutics approved by the EMA and/or Health Canada before the FDA, including mechanistic novelty, likely clinical impact, size of the affected population and FDA review outcome. Results From 2001 to 2010, 282 drugs were approved in the USA, Europe or Canada, including 172 (61%) first approved in the USA, 24 (9%) never approved in the USA, and 86 (30%) approved in the USA after Europe and/or Canada. Of the 110 new drugs approved in Europe and/or Canada before the USA, 37 (34%) had a novel mechanisms of action compared with drugs already approved by the FDA, but only 10 (9%) were for conditions lacking alternate available therapies in the USA at the time of ex-US approval—of which the majority (9/10; 90%) were indicated for rare diseases. 12 of the 37 agents with novel mechanisms of action approved first in Europe and/or Canada (32%) had their initial FDA submissions rejected for safety reasons—including 2 drugs that were ultimately withdrawn from the market in Europe due to safety concerns. Conclusions If enacted, reciprocal approval legislation would most likely benefit only a small number of US patients receiving treatment for rare diseases, and the benefit may be somewhat mitigated by an increased exposure to harms.