Fixed-dose combination drug approvals, patents and market exclusivities compared to single active ingredient pharmaceuticals

Abstract

Introduction: Fixed-dose combinations (FDC) contain two or more active ingredients. The effective patentand exclusivity life of FDC compared to single active ingredient has not been assessed. Objectives: Trends in FDA approved FDC in the period 1980-2012 and time lag between approval of FDC and single active ingredients in the combination were assessed, and the effective patentand exclusivity life of FDC was compared with their single active ingredients. Materials and Methods: New molecular entities (NMEs), new therapeutic biologics license applications (BLAs) and FDC data were collected from the FDA Orange Book and Drugs@FDA. Analysis includedFDC containing one or more NMEs or BLAs at first FDA approval (NMEs-FDC) and only already marketed drugs (Non-NMEs-FDC). Descriptive, Kruskal-Wallis and Wilcoxon RankSum analyses were performed. Results: During the study period, the FDA approved 28 NMEs-FDC (3.5%of NMEs) and 117 non-NMEs-FDC. FDC approvals increased from 12 in the 1980s to 59 in the 2000s. Non-NMEs-FDC entered the market at a median of 5.43 years (interquartile range 1.74, 10.31) after first FDA approval of single active ingredients in the combination. The Non-NMEs-FDC entered the market at a median of 2.33 years (-7.55, 2.39) before approval of generic single active ingredient. Non-NME-FDC added a median of 9.70 (2.75, 16.24) years to thepatent and exclusivity life of the single active ingredients in the combination. Conclusion: FDC approvals significantly increased over the last twenty years. Pharmaceutical companiesmarket FDC drugs shortly before the generic versions of the single ingredients enter the market extending the patent and exclusivity life of drugs included in the combination.