Active and passive surveillance of enoxaparin generics: a case study relevant to biosimilars

Abstract

Objective: This retrospective analysis assessed the capability of active and passive safety surveillance systems to track product-specific safety events in the USA for branded and generic enoxaparin, a complex injectable subject to immune-related and other adverse events (AEs).

Methods: Analysis of heparin-induced thrombocytopenia (HIT) incidence was performed on benefit claims for commercial and Medicare supplemental-insured individuals newly treated with enoxaparin under pharmacy benefit (1 January 2009 – 30 June 2012). Additionally, spontaneous reports from the FDA AE Reporting System were reviewed to identify incidence and attribution of enoxaparin-related reports to specific manufacturers.

Results: Specific, dispensed products were identifiable from National Drug Codes only in pharmacy-benefit databases, permitting sensitive comparison of HIT incidence in nearly a third of patients treated with brand or generic enoxaparin. After originator medicine’s loss of exclusivity, only 5% of spontaneous reports were processed by generic manufacturers; reports attributable to specific generics were approximately ninefold lower than expected based on market share.

Conclusions: Claims data were useful for active surveillance of enoxaparin generics dispensed under pharmacy benefits but not for products administered under medical benefits. These findings suggest that the current spontaneous reporting system will not distinguish product-specific safety signals for products distributed by multiple manufacturers, including biosimilars.

Keywords:

• biosimilar
• enoxaparin
• pharmacovigilance
• safety surveillance

Acknowledgments

The authors acknowledge Patrick Little, PhD, and James Balwit, MS, whose work was funded by Amgen, Inc., for assistance in writing this manuscript. The authors acknowledge Griselda Saldana, an employee of Amgen, Inc., for her assistance with AERS data collection. Research support: Funded by Amgen, Inc. Previous presentation: these data were presented in part at the Midyear Clinical Meeting of the American Society of Health-System Pharmacists, Anaheim, CA, USA, December 7−11, 2014

Declaration of interest

This work was sponsored by Amgen, Inc. G Grampp, T Felix, M Malecki, and JM Sprafka are employees of and own stock and/or hold stock options in Amgen, Inc. G Grampp and T Felix have provided expert testimony on behalf of Amgen, Inc., in support of legislation in US states that allow for automatic substitution of FDA-approved interchangeable biologic products with provisions to communicate and record biologic product dispensed. M Bonafede is an employee of Truven Health Analytics, which was awarded a research contract to conduct a portion of this analysis. E Li has received honoraria for serving on advisory committees for Amgen, Inc., and Hospira, and for service on the speakers’ bureau for Pfizer.

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