In part 1 of this conversation, Dr. Oskouei and I take a deep dive into biosimilar-to-biosimilar switching, a potentially confusing topic that will grow in importance within the next couple of years. (Note: See also the BR&R post on a new study released this week on the safety of biosimilar-to-biosimilar switching—S.M.)
Stanton Mehr, Content Director, BR&R: Welcome, Sonia! This topic is certainly a favorite of mine, because very few people take the time to consider it fully. You brought it up at a biosimilars meeting in Boston in late June, and I thought this would be a good time to give it some visibility. So, let’s do our best to clearly differentiate, first of all, what we mean by “biosimilar-to-biosimilar switching.” How’s this different from automatic substitution, where we are switching to a biosimilar from a reference product?
Sonia Oskouei, PharmD: When we refer to biosimiliar-to-biosimilar switching, we’re talking about a scenario where multiple biosimilars are available for the same reference product. This is a very real scenario today in several drug categories. The patient may be initially prescribed a reference biologic and is then moved to Biosimilar A, and then the biosimilar-to-biosimilar switch would be to Biosimilar B for that same reference product. On the other hand, a new patient may first be prescribed a biosimilar and then they switch to another biosimilar for the same reference product.
BR&R: Let’s bring this scenario to ground level and consider the case of Mr. Jones. He’s been using the infliximab reference product Remicade® for many years to treat an autoimmune condition. Last year, his health plan decided to cover the biosimilar Inflectra® (and excluded Remicade); his provider did not object to the switch. This year, Mr. Jones changed health plans, but the new plan only covers the newest biosimilar, Avsola®. He will have to switch from one biosimilar to another. This is not an uncommon occurrence.
However, in its technical definition of biosimilarity, the Food and Drug Administration (FDA) does not address the comparability of one biosimilar to another—only to the reference product. Therefore, from a regulatory standpoint, Biosimilar A and Biosimilar B are not biosimilar to each other. What are the implications of this?
Oskouei: You’re spot on from a regulatory standpoint. This gets to the question I asked at the conference. As it stands today, the FDA is not responsible for considering whether one biosimilar is biosimilar to another.
I would say that there is greater demand for data on this topic, particularly in the immunology space—your infliximab example, and next year with adalimumab, and soon after with ustekinumab, tocilizumab, etc.
Oncologists’ Comfort With Biosimilar-to-Biosimilar Switching
Oskouei: We’ve seen this scenario play out from payer-driven initiatives to prefer one drug over another, like you mentioned. This has already occurred in the oncology space, too. Oncologists have a high level of comfort; our latest market research show that the majority feel comfortable even switching between biosimilars.
BR&R: Are oncologists switching patients to a different biosimilar between treatment cycles?
Oskouei: Even within the same treatment cycle. That speaks to the clinical confidence that oncologists have with these agents.
Some practices are even monitoring quarter-to-quarter trends in average sales price in an effort to decide which drug (biosimilar or biologic) makes the most sense to use. That may result in some switching among biosimilars.
If a practice switches between biosimilars for the same reference product, the conversation with patients may be very simple. If the patient asks, “Hey, this name looks different.” The response is, “Oh, it’s the same treatment, just a different manufacturer.”
BR&R: The evidence from Europe in terms of biosimilar switching, even with the adalimumab biosimilars (which were launched in October 2018), has been reassuring. The studies on biosimilar-to-biosimilar switching have not reported significant negative outcomes.
Injector Device Differentiation
BR&R: There is no reason why these data cannot be extrapolated to the U.S. population. What about any differences in injector devices? Are there significant differences among them that can raise issues for biosimilar-to-biosimilar switching?
Oskouei: The human factors associated with a specific device and the resulting ease of administration—or risk or potential failure to administer—could be worth considering when a patient is self-administering. It will be interesting to see how these perceptions play out in the adalimumab category.
BR&R: Historically, payers have not heavily weighed the device types or patient preference for device types when making coverage decisions, particularly when many choices are available. Sonia, many of your organization’s clients are health systems and providers. Do you see health systems and physician practices putting a lot more weight on the type of administration device?
Oskouei: Yes, I do believe that they will put greater weight on the device. From current engagements with our health system network, along with my own previous experience practicing within a health system, we know that product characteristics such as device can absolutely influence formulary decisions. We might receive samples of a novel device for insulin, for instance. As part of our assessment, we would check to see how the device and package would fit into the automated dispensing machines to ensure optimal inventory management and pharmacy-nursing operations so that the treatments can be easily accessed for patients located in different hospital units. Ease of use for patient administration is naturally another important factor. These health care stakeholders understand how to evaluate products beyond clinical and financial characteristics. That’s why I believe the device will play a role in formulary decision making, particularly with providers.
BR&R: You mentioned insulin. It’s has been the poster child for device innovation over the years. I participated in some payer market research, more than 15 years ago, on a new insulin autoinjector. This one device was created for use by elderly people with poor vision and who have difficulty handling the small dials on injector pens. The manufacturer made it much easier to see the large numbers on the dosing dial and perform the administration. In that case, the payers were very impressed by the device. Many decided to cover this device for specific populations. However, I’ve never seen another case where payers thought the device made a big difference.
In part 2 of our conversation, which will be posted next week, Dr. Oskouei and I will discuss several other interesting aspects of switching among products within a drug category, including biosimilars and follow-on agents, the potential barriers to switching in the ophthalmology category, and how to collect data on biosimilar switching.