Mark D. Pegram, MD, highlights the gradually evolving landscape of biosimilars and provides insight on how they can shape the US market.
Mark Pegram, MD
It is only a matter of time before more oncologic biosimilars become available as patent expirations are upcoming for several reference products in the field, said Mark D. Pegram, MD.
The European Union can be used as a blueprint of how the biosimilar market could quickly rise to prominence in the United States. Europe is a few years ahead of the United States in terms of patent expirations, Pegram said, and biosimilars have since taken off.
Pegram, co-director and professor in the Molecular Therapeutics Program and director of the Breast Oncology Program at Stanford University Comprehensive Cancer Center, said that although it is too early to attach a concrete discount rate with biosimilars, a potential 25% or 30% cost reduction represents billions of dollars in overall savings.
For those who are skeptical regarding the equivalence of biosimilars, Pegram mentioned the complexity of manufacturing biologic agents. Every molecule in a specific batch can be slightly different from another; it is almost guaranteed that these drugs vary significantly from batch to batch, he said. However, the FDA has also set rigid guidelines for biosimilar products.
In an interview with OncLive, Pegram highlighted the gradually evolving landscape of biosimilars and provided insight on how they can shape the US market.Pegram: Biosimilar drug development in oncology is a very fast-paced and exciting field. An opportunity presents itself because of patent expirations that are upcoming in the next couple of years for several biologics currently on the market. As those patents expire, that creates a framework for more biosimilars to be used commercially. Historically, non-oncology biosimilar products tend to be cheaper; consequentially, this opens the doors to new markets on a global scale.
This is particularly the case in some other countries where they literally do not have access to some of the generic drugs because of how costly they are. In each case of non-oncologic and supportive oncology care products, biosimilar products expanded the market significantly when they became available. This is good for patients. Now, we have opportunities for patients that were not there before because of cost.
Moreover, the rise of biosimilars has cost-saving factors, even for insured populations in the United States. The money that used to be spent supporting profit margins for pharmaceutical companies can now be spent on research and other [development efforts].In terms of cost, it is true that manufacturing a biologic drug product is very complex and very expensive. Biosimilars will not be [discounted 50%]; let's just assume that. It will not be that significant of a cost difference. However, it could be a one-third discount for patients—this is more in line with projections we have seen in recently published literature. These won't be “fire sales” by any stretch of the imagination, but because the current products are so expensive, 25% or 30% off that price is still going to equate to billions of dollars in savings.
This has already played itself out in Europe because their patents expired a few years before they will in the United States. Biosimilars have taken off at a brisk place there. Based off of Europe's experiences with these drugs, we have a pretty longstanding track record of what to expect in the United States in the near future. There is just no doubt that biosimilars will gain traction.
In terms of similarity of these large, complex biologic molecules that are manufactured from living cells, it is almost guaranteed that every molecule in a specific batch will be slightly different from each other. Naturally, there are going to be post-translational modifications, some of them even clinically important. However, as we grow into biosimilars, we will be able to measure those attributes so precisely that we can come up with a panel of important attributes and compare it head-to-head with the reference products.
We’ll be able to show that it is highly similar on all fronts, in terms of structure, function, and binding to its target. These are all measurable in the laboratory and they are measured to guarantee similarity. Those data are then handed over to regulators to define biosimilarity. This is obviously a requirement—the FDA has put forth strict guidelines on this. We then have to do clinical trials to further ensure [biosimilarity].In the wake up of the recent midterm elections, my understanding is that both political parties are aligned in that we need to do something here. This is discussed from a very general perspective, but there is no doubt that this will extend to oncology products since they are among the most expensive. We will soon see some important changes at the federal level—new legislation to start the process of cost controls. I'd like to at least see some sort of articulation from government that this is a priority in the short-term.There is always the consideration of dose and scheduling of drugs that clinicians can be mindful of. As we speak, there are many clinical trials that are essentially de-escalation trials for patients with very low-risk disease. If patients will do just as well with less or even no treatment, we have to consider this or at least see if it is feasible. This is potentially a very good thing. It is a “home run” if these ongoing trials turn out to be successful.
This has been brought on by the advent of new diagnostic assays. Multigene testing in breast cancer is a perfect example where we have been able to eliminate the need for chemotherapy in a high fraction of patients who have targetable genes.As soon as biosimilars hit in a big way in the United States, what we are going to wrestle with the most is the concept of extrapolation. Since all the biosimilars will be approved on the basis of 1 or 2 clinical trials, is this enough to instill confidence in physicians and patients? Different people are going to certainly have different levels of comfort in replacing the reference product with a biosimilar.
Can you pull the data from these registration trials and apply it, not only to practice but maybe even other tumors? For example, the trastuzumab (Herceptin) biosimilar is approved in breast cancer and gastric cancer, but the trials testing this product were only in breast cancer. Therefore, this is going to be a real challenge [going forward].
In addition, biosimilars have not yet been tested in combination. Can we use them with impunity in combination with chemotherapy or other antibodies? We are going to need high confidence in the quality attributes we define as important for biosimilarity. We will also need the FDA and other regulators to back our confidence by approving these agents.