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Robert M. Rifkin, MD, FACP, discusses details of bringing biosimilars to market, ongoing challenges, and the need for education of these products.
Robert M. Rifkin, MD, FACP
The mission of utilizing biosimilars in oncology is to increase access to therapeutic agents while decreasing costs, but education on this class of drugs will be imperative in seeing this through, explained Robert M. Rifkin, MD, FACP.
“We really have to see these succeed by making them hassle-free for patients and providers,” said Rifkin. “We have to educate the patients on what a biosimilar is and why they are getting it, and hopefully they’ll have a reduction in their out-of-pocket cost.”
While biosimilars are poised to play an integral role in the oncology market, Rifkin added that there still needs to be a deeper understanding of these agents and how the data showcasing their similarity to reference products is different, but it is still high-quality data.
In an interview with OncLive, Rifkin, of medical oncology/hematology at Rocky Mountain Cancer Centers of The US Oncology Network, discussed details of bringing biosimilars to market, ongoing challenges, and the need for education of these products.
OncLive: How would you describe the evolution of biosimilars in oncology thus far?
Rifkin: To understand the impact of the biosimilars in oncology, you need to go back to the first one that was approved, which was a Sandoz product; it was the biosimilar filgrastim (Neupogen), which was Zarzio. [That] was the first biosimilar to enter the oncology market. It was a supportive care drug and, initially the price break wasn’t really enough to see uptake, because as all of us know in biosimilars, the idea is to increase access and decrease costs. However, as the market adjusted, appropriate price reductions took place, and there was a very rapid uptake—certainly in our network and various other market sectors as well.
Then the next thing that came was, once again, a supportive care drug—if we exclude the inflammatory space, just limiting it to oncology. That is really when the first biosimilar pegfilgrastim (Neulasta) came out. That one has had a slower uptake, and there are several competitors for that in the market as well; therefore, these were kind of a “ho-hum” but at least access was going up and price was going down.
But really, what is happening now is we are about to see a big change as the therapeutic monoclonal antibodies are entering the market. These would be biosimilars to complex molecules, certainly in the bevacizumab (Avastin) and trastuzumab (Herceptin) areas. As your readers know, Amgen launched a couple of those and there will be several other launches before the end of 2019. This is a bit different than the supportive care area in that now people may be on these a lot longer and in the maintenance settings in some case—now with therapeutic intent. Despite lots of efforts in education, the uptake of the new therapeutic biosimilars in oncology will be slow, and we have mostly seen that in Europe.
Finally, after many years, we are starting to see the biosimilars in oncology. Uptake is slow, but the pace of the uptake will increase once education is complete and physicians and providers have a comfort level of [using these new drugs]. They are finally starting to take a solid place in oncology.
What are the benefits of using biosimilars compared with the reference products, besides cost?
This is a bit of a difficult question because cost is the primary driver; all of these molecules have satisfied the biosimilarity exercise and gained approval in the 351(k) pathway. The benefits are really going to roll up to the patients in terms of increased access and decreased costs. In order to really succeed, it’s a little bit more than just writing a different drug on a piece of paper and an electronic prescription.
Remember, all of these drugs are essentially the same and satisfy the biosimilarity exercise. In this day and age, cost will be the primary control driver and people need to realize that some of the uptake will be driven by payers, and not physicians or manufacturers. That will be different [with biosimilars]. Recently, UnitedHealthcare is in the process of making a decision where biosimilars will be preferred over the originator in several broad classes and therapeutic areas. The idea is to make it hassle-free for all of the stakeholders and pass on a cost benefit to the patients.
Are there certain criteria that payers may use to decide whether or not to use biosimilars?
It is all about cost, and then you will hear a lot about rebates and discounts that are presently being discussed in the Trump administration for price control. Payers are going to have the spotlight for determining who gets what, and realistically—in the case of breast cancer where you have a lot of biosimilars for trastuzumab to launch—I can’t envision carrying all of the potentially 5 FDA-approved drugs that are going to launch [at once].
There are going to be decisions at the formulary level as well; maybe you carried the originator molecule and then you look among the biosimilars, and you have a preferred one in your group. It is very complicated. What you will see though is physicians and other providers leaning toward the biosimilars [to switch to]. We have published a paper about switching in biosimilars and we reviewed a very large number of studies and patients, and we didn’t see any safety signals for switching or loss of efficacy.
There are 5 FDA-approved trastuzumab biosimilars and 2 rituximab (Rituxan) biosimilars. Will there be a point where there is too much competition among the biosimilars?
That is a very good question. What happens is the later you are entering the market, the more difficult it becomes. If you are spending anywhere between $300 and $500 million to develop this therapeutic biosimilar, and you’re fourth to market, that is going to be a difficult business plan to execute. There may be a lot out there, but a lot of them fail along the way—whether it’s during the biosimilarity exercise or in the business plan of a major manufacturer.
[The manufacturer] may look and say, “Well, there are 6 of these in the US in the market, and I can’t see where the seventh fits within our business plan,” so it might go to a different market overseas. I don’t think there will be many of the same on the shelf. At some point, when you’re late to the market, or if you don’t have something very unique, you won’t be able to recover your costs to the development because competition will be too difficult.
What are the main challenges that remain regarding biosimilars in oncology?
One that is clearly identified is education. Within our organization, we have a whole bunch of educational [resources] available to pretty much anyone who wants to learn about biosimilars. We have to get rid of the myths, and there are a lot of those out there. The challenge is educating all of the stakeholders, then making it hassle-free for providers to order it and patients to get it in a timely fashion. There are just too many layers for getting things approved; if we could make it “leaner and meaner,” that would make it much easier.
We have a number of patient-facing materials, as do others, including the FDA. Everyone is working very hard on education, and in our group we do webinars regularly. For many years, all we were doing were presenting drugs that were out there and nothing got out through the regulatory pathway. Now, we have an abundance of drugs that are satisfying that. Education is one of the biggest things, and you have to convince people—everyone who has a touchpoint—to order the biosimilars.
What are some of these myths that need to be debunked?
The way [oncologists] were trained is, when you develop a drug in conventional oncology, clinical trials carry the day. If you can do a big, randomized trial with a registrational status and show your [drug] is better than the currently available drug, that is a good thing. In biosimilars, there is a heavy reliance on the analytics in clinical trials; there are sometimes not even required pharmacokinetics (PK) and pharmacodynamics (PD) if you satisfy the analytics.
The big difference is convincing providers that with the way the 351(k) pathway was provided and designed, you don’t need large clinical trials. In fact, even the FDA discourages doing animal toxicology studies [for biosimilars], which are the things we grew up with as oncologists. It is turning the pyramid of drug development upside down. Analytics are now the largest component, comprising PK, PD, and immunogenicity. At the end of the day, the only reason you do a trial is if there is any residual uncertainty between the originator and the biosimilar. That is the big difference.
What other research in biosimilars would you like to share?
A lot of what we are working on is to see, when they enter the market, what happens in terms of health economics and outcomes research. We have some projects going on there, where you can see at how it all works; a lot of it is tracking things and seeing what happens, watching the uptake, watching the market, and watching prices. It is our goal to hold down the cost and really make an increased access, and decreased costs.
Are there recent data that have readout with biosimilars that you would like to highlight?
When you do [a trial comparing a biosimilar with its reference product], the result should be highly similar; it can’t be worse or better than the originator. Some of those studies get published and some don’t. Some get a lot of media attention, such as the HERiTAge study in breast cancer, but everyone is waiting for phase III trials, which really don’t exist. Therefore, when people sit down from an outside agency to do an independent review and look at the totality of evidence and start to present that to their peers, they [need to] understand that there is high-quality science behind all of this. One of the myths is that there are not enough data; it can’t be any good compared with the originator. Really, it’s the opposite because you have done a tremendous number of analytics, and you know, from a pure science structure standpoint, way more about the biosimilar than was ever learned from the originator.