In April, the Center for Biosimilars reported on a study of infliximab switching in patients with psoriasis. The researchers found no differences in safety or effectiveness in 24 patients taking infliximab biosimilars. I had to read the copy twice; it took me a couple of moments to understand the significance of this small study.
Beyond the disease state, the interesting part of this investigation is that the switch was not made between the reference product (Remicade®) and a biosimilar, but between two biosimilars (Inflectra® and Renflexis®). With today’s focus on the interchangeability guidelines and the well-publicized NOR-SWITCH studies, the potential questions around biosimilar to biosimilar switching is often overlooked.
As more biosimilars are approved and launched for several disease categories, this concept will prove to be as important as the reference biologic to biosimilar switch (or vice versa). The reason is simple: Coverages among plans will vary, and as patients change plans, they may need to change from one biologic version of the reference product to another. It is easy to visualize the scenario where Big Health Plan covers biosimilar A and City Health Plan covers biosimilar B, and patients changing plans every year or so might need to switch therapies. Then biosimilar to biosimilar switching becomes a common occurrence.
In 2019, this is not yet the new normal. Infliximab coverage is commonly limited to Remicade, and if a plan or insurer decides to cover another version of infliximab, payers usually choose one biosimilar to improve the deal they receive. Therefore, a patient changing insurers at the end of the year will most likely not have switch from one biosimilar to another (e.g., from Inflectra to Renflexis). They might, however, have to change from the innovator product to a preferred biosimilar.
For the other competitive, marketed biosimilar drug categories (filgrastim and pegfilgrastim), therapies are given less on a chronic basis, so the need for mid-regimen switching among biosimilars is pretty small.
When the FDA evaluates a biosimilar, it requires comparative physiochemical and pharmacokinetic analyses between that biologic and its reference agent. The FDA cannot find that two infliximab biosimilars are biosimilar to each other. That only stands to reason and the laws of transitivity. Yet, possible differences in immunogenicity, for instance, may cause some concern for physicians and patient groups. This has not been found to be a concern in Europe, where multiple biosimilars (including infliximab) have gained years of experience. Experience is also accumulating with another immunologic biosimilar, adalimumab, as multiple versions are widely in use since October 2018.
Payers may be less concerned, and for basic reasons: (1) they anticipate that FDA approval is sufficient proof of safety and efficacy, (2) they seek to cover the most cost-effective products, and (3) the scenario has not yet arisen to any degree. In the US, switching between biosimilars is still mainly a hypothetical problem.
The benefits of interchangeability in this case are hypothetical as well. One might expect that two adalimumab agents that are designated interchangeable to an innovator product would likely be associated with fewer fears of safety problems when switched with each other. To use a well worn cliche, we’ll cross that bridge when we come to it.