Restating the Record on Biosimilar Safety and Efficacy

At this point in time, it may be a bit more difficult to find professionals who are convinced that approved biosimilars are not as safe and effective as the originator agents. The call of those manufacturers defending their long-time marketshare is being drowned out by (1) informational sites published by major pharmaceutical manufacturers and marketers, and (2) the facts presented by the governmental agency with the most experience approving and regulating biosimilars—the European Medicines Agency (EMA).

Several manufacturers have excellent resource sites on how biosimilars are manufactured and how they differ from the originator products. These include “minor” players such as Amgen, Merck, Pfizer, among others. Their sites are pretty informative, and do not seem to be developed strictly as a marketing platform for their biosimilar products. As a group of resources, they are contributing to a public educational effort to ease potential concerns with biosimilars.

The immunogenicity and extrapolation issues are historically the greatest points of sensitivity to patients and providers. The EMA issued a report in May 2017 that summarized its findings over 10 years of biosimilar surveillance—there is no evidence of safety problems or efficacy problems with approved biosimilar products since the first licensed product. “Extrapolation is not a new concept but a well-established scientific principle used routinely when biological medicines with several approved indications undergo major changes to their manufacturing process (e.g. to introduce a new formulation). In most of these cases, clinical trials are not repeated for all indications and changes are approved based on quality and in vitro comparability studies,” states the report. Moreover, “Over the last 10 years, the EU monitoring system for safety concerns has not identified any relevant difference in the nature, severity or frequency of adverse effects between biosimilars and their reference medicines.”

Although this is absolutely true for the first-generation of biosimilars, the monoclonal antibody biosimilars have been licensed by the EMA more recently, with the first being infliximab in 2013 and the last being rituximab and etanercept in June 2017. Over time, utilization and evidence will accumulate to support their safety and effectiveness in real-world practice and across multiple indications. Yet, the potential for immunogenicity, which several switching studies have shown is low, will eventually fade as a concern.

The “Eprex Incident” of 1998 remains the sole alarm bell for a true product safety problem related to the manufacture of a biosimilar-type of product (predating by several years the introduction of biosimilars and biosimilar approval regulations, even in Europe).

Obviously, the past does not predict the future. That is one reason why organized surveillance efforts are needed both in the EU and in the US to capture any safety signals. However, it does seem that products making it through the regulatory approval systems are delivering the promised results.


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