Systematic Review Finds "Low Risk" of Safety Concerns or Loss of Efficacy Following Switch to a Biosimilar

Being able to switch from a reference product to a biosimilar is important for 3 reasons, explained Hillel Cohen, PhD, executive director of scientific affairs at Sandoz, during his presentation at SMi Biosimilars USA Conference in Iselin, New Jersey, held November 14-15, 2018.

Allowing “biosimilars to [be marketed to] established patients is critical for commercial success and sustainability of the biosimilar industry, it maximizes cost-savings to the healthcare industry, [and] determines the initial market for a biosimilar,” he explained.

Without the ability to switch patients to a biosimilar, the therapies would only be available for biologic naïve patients, and therefore would limit patient access. Of note, the FDA has yet to release a final guidance document around switching (referred to as interchangeability), although it is expected to be released by May 2019.

Cohen said that there are a few different kinds of switching scenarios available: a switch from the reference product to a biosimilar as a "one-time single switch;" multiple switches where a patient is switched from a reference product to a biosimilar, then back to a reference product; or a single switch where a patient is switched from one biosimilar to another.

Since the introduction of biosimilars, switching has been a commonly discussed, if not sometimes controversial, topic throughout the industry. Many questions surround the practice of switching, such as “Is it safe, will it lead to increased immunogenicity?” and “Will patients get the same benefit if switched?” However, Cohen himself sought to decipher if there were data to help assess these hypothetical concerns.

In a systematic review published in March 2018, Cohen and his colleagues analyzed data comparing reference products with biosimilar switching conducted in 14,225 patients from 90 separate studies. The review covered 14 different disease states, 7 approved reference products and their respective biosimilars in both the United States and the European Union from 1993 to June 30, 2017. Specifically, the review compared safety, efficacy, immunogenicity, and adverse event data from both the reference product and the biosimilar.

In total, there were no reported differences in immunogenicity, safety, or efficacy in a majority of the studies (88/90). In addition, the safety profiles of each product were similar to those already known from continued use of the reference medicine.

It is important to note, however, is that there is currently no published data about switching from one biosimilar to another. Instead, explained Cohen, there is only anecdotal evidence, such as Kaiser Permanente switching patients to growth hormones from different manufacturers in the United States. In Poland, national tenders led to switching of different growth hormones year over year, and similarly, in Hungary, national tenders switched patients to different versions of filgrastim biosimilars year over year.

Cohen stated that there is an upcoming opportunity to see the effects of switching from one biosimilar to another in 2019, as both the US Veterans Administration and Norway will switch from one biosimilar infliximab (Inflectra) to another (Renflexis).

“The great majority of studies did not report differences in safety, efficacy, or immunogenicity after a single switch event compared to patients that were not switched…Overall, the results suggest a low risk of either a safety concern or a loss of efficacy after switching to a biosimilar,” he said.