Dramatic change has marked the United States health care system for several years. One particular factor that will affect the future of health care is biosimilars. The European Medicines Agency approved its first biosimilar product in 2006; the United States biosimilar market remains in its infancy. The United States must look to the European Union as biosimilar adoption continues to grow.
Dramatic change has marked the United States health care system for several years. One particular factor that will affect the future of health care is the development of biosimilars. Although biosimilars are still in their infancy in the United States, the European Union (EU) has more than a decade of experience with these products. The US market continues to develop by utilizing learning, adapting processes, and assessing impact from the EU market.
The Biologics Price Competition and Innovation Act (BPCIA), passed in March 2010, provides manufacturers with an abbreviated approval process for biologics that were shown to be highly similar to, or interchangeable with, the innovator drug. The BPCIA provided biosimilar manufacturers with a pathway that allowed them to use existing safety and efficacy data from the innovator product as part of the approval package, thereby reducing the cost of development to the biosimilar manufacturer.1
The regulatory approval framework for biosimilars in the United States mirrors that of the EU in many ways. Both agencies share specific definitions of the features of a biosimilar medicine: that these agents have physical, chemical, and biological properties highly similar to the reference agent; that no differences are expected in clinical performance; and that minor variability is allowed only in such a way as it does not impact the safety and efficacy of the biosimilar.2
The first biosimilar, Omnitrope, was approved by the European Medicines Agency (EMA) in 2006. Since then, the EMA has approved more than 20 biosimilars.3 Contrast that with Zarxio, the first biosimilar approved in the United States, which was not approved until March 2015.4 To date, seven biosimilars have been approved in the United States, including Zarxio, but only three are commercially available (Zarxio, Inflectra, and Reflexis).5 With so few biosimilar agents currently available here, a lack of familiarity among providers, payers, and patients is understandable. Additional competitive dynamics in the United States market, such as licensing and patent issues, impact the availability of biosimilars.
Simple vs Complex
The so-called “simple molecule” biosimilars (growth hormone, erythropoietin, and granulocyte colony–stimulating factor [G-CSF]) have been available in Europe for more than a decade, and are widely accepted as interchangeable with the originator products. The more recent introduction of the biosimilar infliximab—the first “complex molecule” biosimilar—divided clinical opinion. Across Europe, physicians generally agreed that initiating naive patients on a biosimilar product is appropriate, but because of concerns about immunogenicity and long-term safety, many of them resisted switching stable patients. This led to considerable heterogeneity in the levels of uptake across and even within European markets.
These concerns have largely dissipated with clinical experience and favorable outcomes from switching studies, such as the NOR-SWITCH trial.6 Several national regulatory authorities, including the Dutch Medicines Evaluation Board, Finnish Medicines Agency Fimea, Healthcare Improvement Scotland, Irish Health Products Regulatory Authority, and Paul Ehrlich Institute in Germany, have taken national positions to endorse the interchangeability of biosimilars under the supervision of the prescriber. That said, large pockets of resistance remain, especially in countries that are culturally reticent about the use of generics, such as France and Italy.
Following the introduction of the antitumor necrosis factor (TNF) biosimilars for infliximab and etanercept, attention is turning to the next wave—the oncology biosimilars—due to launch in Europe. The first biosimilar versions of rituximab and trastuzumab—Celltrion’s Truxima and Samsung Bioepis’ Ontruzant, respectively—gained positive opinion from the Committee for Medicinal Products for Human Use after their approvals earlier this year.7,8
Because of marked differences in the disease dynamics of cancer vs the chronic inflammatory diseases targeted by the anti-TNFs, uptake patterns are likely to differ. Given that cancer is a life-threatening illness, oncologists may well be wary of switching patients for fear of jeopardizing their prognosis, especially those nearing the end of their treatment courses. Also, because cancer therapies are associated with much shorter durations of treatment, patient turnover is higher, meaning switching is not going to be a focus for payers in the same way it has been with the anti-TNFs.