In the second part and conclusion of our conversation, Dr. Oskouei and I 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.
Stanton Mehr, Content Director, BR&R: We can learn several lessons about biosimilar switching from the insulin category, related to the topic at hand. For several years, we’ve had follow-on products like Basaglar® and Toujeo® for glargine, and Admelog® for lispro. That’s not even counting Semglee®, which was a follow-on glargine before being designated a biosimilar (and interchangeable at that). With the exception of Semglee, these are not biosimilars, but for all practical purposes, they are really treated like biosimilars. We talk about switching data among biosimilars. How about among the follow-on products? We could also point to the two primary branded rapid-acting insulins (Humalog® [aspart] and Novolog® [lispro]). Switching between these two is also a possibility. Do we have any relevant real-world data?
Sonia Oskouei, PharmD: I believe the need for switching data and the discussion about switching will vary based on therapeutic area and product type. To your point, the insulin category is incredible! We now have six insulin glargines approved—with each one coming with a certain regulatory “labels”—including originator biologic (Lantus®), follow-on biologic (Basaglar®), biosimilar (Rezvoglar®, which is approved but not commercially available yet), and interchangeable biosimilar (Semglee). This dynamic is essentially the result of approval timing and the transition of insulins to be regulated as biologics (in March 2020).
Compared with insulin molecules, monoclonal antibodies are so much larger and represent a whole different level of complexity. There’s a reason why Semglee was the first interchangeable biosimilar approved in the U.S. The FDA’s updated guidance specifically for insulins states that switching studies may not be necessary to gain interchangeable designation, which is appropriate given the relatively simple nature of insulins as biologic molecules and the vast number of years of experience with these products.
BR&R: OK, do we have the need to monitor biosimilar-to-biosimilar switching data and outcomes? If so, who should be doing it?
Oskouei: I am a big advocate for any organization that can act proactively and collect this data. This discussion will happen more and more, and it is where we are heading in immunology. We want to make sure the infrastructure is in place for these data to be captured.
To your point, though, we still struggle a bit in this country with giving the appropriate credibility and weight to the accumulated international data. We really need to leverage as much as we can.
BR&R: Once the adalimumab biosimilars are added to formularies, we will begin to gain a lot of data. Whether we are in a position to capture may be a question for the BBCIC. [Note: In a separate conversation, Dr. Cate Lockhart, Executive Director of the Biologic and Biosimilar Collective Intelligence Consortium, told us that the organization has begun investigating the descriptive factors necessary to collect biosimilar-to-biosimilar switching information from the Consortium members’ claims databases. She noted that there may be a data lag of perhaps 18 months between the time the first adalimumab biosimilar is launched and enough data are collected and analyzed.] This might then, using U.S.-derived data, completely put the issues of safety and efficacy to rest.
In any case, I do believe that some segments of the health care system—payers at least—already accept it as this is a fait accompli. And payers will be the major force behind the demand for switching.
Oskouei: To your point, it’s already happening. The payer landscape is a strong driver of switching. We saw that happen even earlier this year when one key regional payer went from preferring one particular infliximab biosimilar, to then preferring both a different infliximab biosimilar and the originator product. Of note, the new infliximab biosimilar that was being preferred (at parity with the originator) had the lowest market share at the time, too. So in this scenario, patients could be in the position to switch to another biosimilar or even back to the originator product. This is just an example of how the managed care landscape can, and does, influence adoption patterns.
Biosimilar-to-Biosimilar Switching and One Touchy Subject
BR&R: Among these individual drug categories, do you think one stands out that might be more risky than others in terms of biosimilar-to-biosimilar switching?
Oskouei: The ophthalmologic agents injected intravitreally stand out. There may be less clinical confidence there than in some other drug categories and perhaps some overall hesitation with biosimilar switching.
BR&R: I guess it’s a visceral reaction really, when talking about agents that act on the retina.
Oskouei: Following ranibizumab, we have aflibercept, which now is up to about eight candidates in the pipeline. That number isn’t too different than the number of adalimumab biosimilars, which isn’t just a coincidence. In fact, if you look at the top 10 selling pharmaceuticals in 2021, aflibercept is number 9. This is just a fascinating space, because beyond the biosimilars, there continues to be significant advancements in the treatment options for these retinal conditions, competing with both the existing originators and biosimilars. I really do enjoy focusing on it.
Subcutaneous Infliximab: What Does That Mean for Biosimilar Switching?
BR&R: I’d like to get your take on another aspect of the biosimilar-to-biosimilar switching scenario. On the horizon, we have the potential approval of Celltrion’s subcutaneous (SC) injectable form of infliximab. Obviously, this agent is derived from Celltrion’s Inflectra/Remsima infusible biosimilar. However, it requires approval not as a supplemental biosimilar application but as a new brand. It would offer the advantage of a quick self-injection at home versus an hours-long infusion at a provider office or infusion center, should it be approved in the U.S. Do you think there would be significant pushback if payers wanted to move patients to the SC formulation? What will happen in this situation?
Oskouei: That’s a very good crystal-ball question. I’ve tried to understand it by reviewing the performance of the SC version in Europe, where it is already available. There’s not a lot of adoption so far.
BR&R: According to Celltrion’s recent earnings report, the market uptake has been relatively low—in the single digits in certain regions. Now, U.S. payers might be more aggressive, given the right price, and on the pharmacy benefit. That may result in a different cost-sharing scenario for patients (possibly higher out-of-pocket costs).
Oskouei: I’m thinking about a couple of things here. You’re right, the SC form will be considered an originator biologic by the FDA. I also think certain physicians will view patients’ infusion office visits as opportunities for pharmacovigilance or monitoring. It is another opportunity to maintain engagement with the patient. It may not be a fit for all.
The SC formulation will have its place though. This type of product or dosage form expansion will continue to occur, and I view it as another positive that results from a healthy, and successful biosimilars market in the U.S. Innovation is further ignited through enhanced competition, which ultimately brings new innovative treatment options to patients that further improve outcomes. Those innovations may be through novel mechanisms of action, dosage forms, dual-product combinations, or other types of treatment advancements.