Bruce Feinberg, DO: Hello, and welcome to this Center for Biosimilars® Peer Exchange® titled “Understanding and Improving Access of Biosimilars in Oncology.”
I am Dr Bruce Feinberg, vice president of clinical affairs and chief medical officer at Cardinal Health Specialty Solutions. Joining me today in this virtual discussion are my colleagues Dr Karina Abdallah, Blue Cross Blue Shield of Michigan; Dr Michael Diaz, Florida Cancer Specialists & Research Institute; Kathy Oubre, Pontchartrain Cancer Center in Covington, Louisiana; and Bhavesh Shah, Boston Medical Center health system.
Today we are going to discuss a number of topics pertaining to the use of biosimilars in oncology, including improving market access and the economic impact. Let’s get started on the first topic.
We’re going to give an overview of biosimilars. I know this can be problematic for many of you. I first started speaking about biosimilars on the circuit 6 years ago. For many, this is old hat, but it raises a question to level set on this subject. Despite the awareness that many seem to have, why has the market uptake been so limited? For that reason, it’s worth going back a bit and understanding the basic pharmacology of biosimilars and what differentiates them from generics. We’re not going to belabor this, but we are going to get into some of these basic questions so that it is clear to everyone on this call and also clear why some of these issues may still be confusing to practitioners, particularly in oncology, where availability has been very limited. What are the similarities and differences of biosimilars from biologic reference brands— again, this difference in regard to generics. The naming has gone through changes and iterations for biosimilars. To get us started with that, I’m going to ask Bhavesh to provide a bit of background and give us some of those basic definitions and understandings. Bhavesh?
Bhavesh Shah, RPh, BCOP: Thank you, Bruce. Obviously, there is a very basic definition that we, as health care providers, understand. Biosimilars are biologics that are similar to the reference product with no clinically meaningful differences in regard to potency, purity, and safety. I think the biggest aspect is trying to explain to a patient what a biosimilar is using that definition, so I see that as a gap in patient education. Another gap in regard to biosimilars is interchangeability. We know that it is 1 of those standards that is a regular trade term. A lot of the time, providers and patients think there is a higher designation given to a biosimilar and that if a product doesn’t have that, it doesn’t actually function the same as a biologic.
There’s definitely a lot of provider and patient education that is needed to help close the gap. One of the other aspects that I still see people struggle with is that providers come to me and say, “How is it that the FDA did a phase 3 randomized control trial in 1 indication and then extrapolated it to 7 different indications?” There’s definitely an education gap in terms of the whole process, besides the definition, from my perspective.
Bruce Feinberg, DO: Bhavesh, you bring up some great points. The first point has to do with the clinical trial design by which biosimilars gain their approval. Their comparison to the reference brand was often in a noninferiority trial. We have a trial design in and of itself that is held as more suspect in the world of oncology. Then we have the issue of extrapolation across indications, which is also something that is anathema in oncology, whereas it may be accepted in inflammatory diseases to a greater degree. Then we’ve got this issue of interchangeability, which is problematic. To some degree, interchangeability is difficult even for the reference brand because of the manufacturing process, in which that product continues to evolve. The Rituxan [rituximab] that was manufactured 20 years ago may be very different from the Rituxan that is being manufactured today. Could you touch on that for a moment too?
Bhavesh Shah, RPh, BCOP: Sure. I think the manufacturing is a different aspect, as well. Another myth that I have always heard is that each lot of rituximab is a biosimilar of itself, and that’s not true because the manufacturing process is completely different—it is called product drift—versus a biosimilarity process that is established for a biologic to go through to be approved as a biosimilar. There are actually critical quality attributes that the manufacturing process has established from the reference product and basically, the manufacturer has to meet those critical quality attributes for it to go into production. Outside that reference range, there are implications on the mechanism of action and the potency of the drug. Those reference ranges are established more for manufacturing and not for a biosimilarity product process.
Bruce Feinberg, DO: That’s great. That is the kind of answer that really gets people to open their eyes and say, “Wow, this is more complicated.” This is an aspirin where 21 atoms are going to now be made by someone else who is going to string together 21 atoms, and it’s going to be exactly the same. These are the exact same chemical. There are no differences among them. You can call them something different, but it is what it is. When you get into 20,000 atoms that are not identically strung together, then you have to look not at their chemical signature and identity but more in some kind of a surrogate by which you say they’re equivalent. It almost becomes more about the process of manufacturing than it does the end product.
Michael Diaz, MD: Whenever I’m trying to explain things to patients, as you alluded to, generic medications are a simple molecule that is made in a chemical process in a chemical plant. It has 1 unique structure. These are chains of hundreds, if not thousands, of those molecules that are assembled by a living organism, and by nature, it’s much more complex. There are all sorts of subtle differences that can exist and develop even in the same process over time. Not only that, but whenever you’re looking at it for an indication—and I’ll use filgrastim as an example—there are many different indications for the use of this medication to stimulate the growth of white blood cells. But in each of these indications, they might be stimulated for different reasons. You’re looking at not only different drugs or different biosimilars but also different, unique applications.