Evidence of Pharmaceutical Innovation and Therapeutic Enthusiasm:  Strategies for Patent Extension

In this issue of the Archives, Downing et al¹ present a case report about how a pharmaceutical manufacturer successfully avoided generic competition for one of its blockbuster drugs for more than a decade. The use of patent infringement lawsuits to delay generic competition, a practice called “evergreening,” is common and perhaps well known.

However, for fenofibrate, Abbott Laboratories devised a novel and especially clever approach: the manufacturer reformulated the drug at a slightly different dose, gained approval on the basis of claims of bioequivalence, and then avoided competition because the minor differences in dose prohibited generic substitution. In 2000, for instance, Abbott used efficacy and safety data from previously submitted clinical trials in its “new” drug application and, on the basis of the results of 4 small pharmacokinetic studies, claimed bioequivalence between the approved formulation (Tricor-1 capsules with 67-, 134-, and 200-mg doses) and the new formulation (Tricor-2 tablets with 54-mg and 160-mg doses). No new clinical trials of triglyceride lowering were conducted. In 2001, the manufacturer switched exclusively to sales of Tricor-2 tablets, so that patients taking fenofibrate had to be switched over to Tricor-2 doses during the 6 months before the generic versions of Tricor-1 doses were approved by the Food and Drug Administration. As a result of the minor change in dose, pharmacists filling Tricor-2 prescriptions could not substitute generic versions of Tricor-1 when they finally became available in early 2002, despite the fact that the manufacturer had won approval on the basis of pharmacokinetic evidence for bioequivalence. The manufacturer used these methods repeatedly to avoid generic competition through December 2011.