Mandatory switching of biologic drugs—beware of potential side-effects

Over the last few decades, a growing number of new innovative biologic drugs on the market has completely transformed the management of several diseases. In the past five years alone, more than 60 of these new drugs have been marketed in Canada to treat a variety of serious and disabling illnesses including diabetes, immune system disorders and cancer. Their arrival on the market is very good news for patients, as these medicines, often prescribed as a last line of treatment when other therapies have failed, keep them active and help to significantly improve their health conditions and quality of life.

However, because these drugs are produced from living cells rather than by chemical synthesis, the development and manufacturing processes involved are considerably more complex and therefore more expensive than for traditional drugs. For instance, the manufacturing process for a chemical drug typically requires 40 to 50 critical tests, while the same process for a biologic might require 250 or more. Quality control is even more critical and complications in production potentially more catastrophic. The most important clinical consequence of this variability in manufacturing is that a seemingly small and innocuous change in any one of the steps may induce unintended immune response.

Unlike traditional medicines, protein-based biologic drugs do not have fully defined and reproducible structures, making it impossible to create identical copies. Health Canada allows drugs called “biosimilars” to enter the market only after the patent on the original version of the drug has expired, and the similarity of the two products in terms of both safety and efficacy has been established.

In an effort to lower pharmaceutical spending, provincial governments recently implemented programs to artificially promote market access for these biosimilars. British Columbia set a precedent in May 2019 by becoming the first province to introduce a mandatory biosimilar switching program for non-medical reasons. Alberta has gone even further. As of January 15, 2021, adult patients who require a biologic medication for the first time must begin their therapy with a biosimilar, as the public drug benefit plan will no longer cover originators.

Is non-medical switching well-advised?

At the beginning of the year, Quebec’s Institut national d’excellence en santé et services sociaux (INESSS) conducted an exhaustive literature review on the impacts of mandatory biosimilar switching policies. This review highlighted that for certain populations or certain therapeutic fields "very little or no data are available regarding the safety of biologics switch.” It urged decisionmakers to be cautious, reminding them that mandatory switching for non-medical reasons is generally not accepted by learned societies and clinicians. It is feared that patients who have few treatment options and whose condition is complex may be destabilized.

In the vast majority of European countries, the decision to change a patient's medication to a biosimilar is made by the treating physician. Changing a patient's medication to a biologic therapy for strictly economic reasons is not authorized, except in a few countries. It’s accepted that the treating physician is better able to assess the needs and health conditions of his or her individual patients, and to prescribe the drugs most likely to adequately address them.

Moreover, mandatory switching for non-medical reasons ignores the fact that not all patients respond the same way to medications and can sometimes lead to additional costs to health-care systems. In a recent literature review, researchers at the University of Missouri-Kansas City identified 17 studies that reported an overall increase in costs associated with the non-medical switching of biosimilar drugs. The researchers cite higher rates of surgery (11 per cent), increased use of other medications (13 per cent) and increasing doses of biosimilars (from 6 per cent to 35.4 per cent) as some of the reasons for the cost increases.

Unsurprisingly, patients generally prefer personalized treatment and oppose mandatory switching. Canadian researchers surveyed patients with gastrointestinal diseases and their caregivers, to find out their views on the use of biologic and biosimilar drugs. Of the patients surveyed, 95 per cent said they thought it was important that the decision on the right choice of medication be determined solely by their treating physician, in collaboration with them.

Ultimately, the advent of biosimilars can be seen as good news for patients and physicians—when it increases the range of treatment options available to them and encourages healthy competition between manufacturers. Where reference biologics and biosimilars are allowed to coexist without favouring one to the detriment of the other, price reductions are observed for all products. However, government policies that force biosimilar switching for non-medical and strictly economic reasons may ultimately undermine competition, increase total health-care costs, and act as a barrier to innovation and future access to new biologic drugs for all Canadians.