Julie R. Gralow, MD, discusses the emergence of biosimilars in the United States and globally.
Julie R. Gralow, MD
With several biosimilars approved by the FDA, these agents are now beginning to be used in clinical practice in place of the reference products, explained Julie R. Gralow, MD.
The FDA has approved 5 trastuzumab biosimilars: MYL-1401O (Ogivri; trastuzumab-dkst), CT-P6 (Herzuma; trastuzumab-pkrb), SB3 (Ontruzant; trastuzumab-dttb), PF-05280014 (Trazimera; trastuzumab-qyyp), and ABP 980 (Kanjinti; trastuzumab-anns).
Though the first trastuzumab biosimilar MYL-1401O was approved in December 2017, it did not launch in the United States until December 2019, marking the first trastuzumab biosimilar permitted to be used in place of the reference product for patients with HER2-overexpressing breast cancer and metastatic gastric or gastroesophageal junction adenocarcinoma.
“Biosimilars are a relatively new class of agents, especially in the United States. We've had some growth factor biosimilars for a while in other parts of the world, especially Europe,” said Gralow. “With biosimilars specific to breast cancer, we just had our first one that actually hit the clinics earlier this month in December 2019. We have had 5 trastuzumab biosimilars that have been FDA approved over the past few years, but none of them have hit the clinic until [December 2019].”
Additionally, she added, biosimilars have the potential to alleviate some of the financial toxicity associated with oncology treatments.
In an interview with OncLive® during the 2019 San Antonio Breast Cancer Symposium, Gralow, clinical director of Breast Medical Oncology at Seattle Cancer Care Alliance and professor of Medical Oncology at University of Washington School of Medicine, discussed the impact of biosimilars in oncology, both in the United States and globally.
OncLive: Could you explain the mechanics of biosimilars?
Gralow: Biosimilars are not generics. They're like generics, but because they're a biologic, they aren't exactly 100% identical. Biologics, the big antibodies, are grown up in vats and they're made in cells. There are things about that process that mean you can't control for every single thing about every batch and about every molecule. Therefore, they're kind of like generics, but they're biologics. They're not 100% identical, but for the ones that are and go through the process of FDA approval, there is a whole structure for how these agents get approved. They have to be compared with the original biologic, and they have to have no obvious differences in purity, safety, or efficacy. If they are FDA approved, you can be assured that they've gone through all of these processes which have assured that they are as similar as you can get to the originator.
What impact are biosimilars expected to have in oncology?
Biosimilars have the potential to drive down prices because now you have competition. From a global health perspective, I'm very excited that it will allow these drugs into low- and middle-resource countries that couldn't otherwise afford them. The World Health Organization (WHO) has an essential medication list and it publishes every 2 years. They update the drugs—most of them generic—but drugs that they feel have strong efficacy, cost, and feasibility. If a country can afford it, they should get these drugs on their registry.
Trastuzumab was added several years ago to the WHO’s essential medication list. Now, low- and middle-resource countries are struggling with, first of all, doing good HER2 testing, but also how to incorporate these drugs, pay for them, and get them into our patients where they can offer benefit. There are “copycat” drugs that have been out there that have not gone through this whole biosimilar approval process that are being made and, especially in the low- and middle-resource countries, are being sold and used. They have none of the assurances where they've gone through the testing, have data presented, and are approved by the FDA. Physicians and patients need to better understand what biosimilars are because they have an important role to play in getting access to important drugs and also containing costs.
Why is there still resistance to biosimilars in the United States?
Resistance to biosimilars comes from a lack of education about the process for getting them approved and the steps that are involved. ASCO has done a very nice job of issuing a statement on biosimilars that goes through a lot of these points.
Also, there is confusion around the ability to write for a brand name biologic [in a medical document] and swap it out for a biosimilar. We had that trouble with the growth of the white blood cell growth factors. We would write for a regimen that included [a biosimilar], and then either the insurance company or our pharmacy would say, "No, you have to use [a different biosimilar]."
Then, because these are not generic drugs, in the United States, we have interpreted that as you have to rewrite it again. You can't just swap. Whereas for a generic, with identical chemical structures, you are allowed to swap it out unless the physician assigned [to the case] and said, "No, you can't substitute." However, for biologics, the current pathway is that you have to write for it all over again. That makes it hard.
We haven't even had experience yet with the trastuzumab biosimilars because they're just hitting the clinic, but I think there's going to be frustration around, "My pharmacy makes a deal with 1 [biosimilar]. Yet, this insurance wants me to use another [biosimilar] and this insurance wants me to use another [biosimilar].”
How do we do that? We would go crazy because we can't keep track of all of that. We have to make it easy with a better understanding of what these drugs are and how they got approved. We need to work on a better method for writing for one [biosimilar] and [making it] okay to swap out for another [biosimilar] without having to go through a whole new order all over again. We should also avoid having 5 different [biosimilars] that, depending on what insurance company or what pharmacy [the patient] goes to, are available. That will really help with some of the resistance [against biosimilars], as well.
What should physicians consider when recommending a patient for biosimilar versus the original drug?
From my perspective, since there are no differences in purity, safety, and efficacy, I don't have a preference. I am not saying, "This one's better for you. I'm strongly wedded to this one." As a physician, I don't see a distinction and that's the whole point. They've gone through this process where I can't tell you there's a distinction. In the big scheme of things, what's going to drive it is going to be cost. It's not going to be the physician who's making that decision. It's going to be the payers and the pharmacies.
The trastuzumab biosimilars are the first to hit in breast cancer, but we've got a whole bunch of other biologics. Think of all the antibodies and the antibody-drug conjugates that we're using right now. As they get poised to go off patent, you are going to have a biosimilar for all of those. Bevacizumab (Avastin) biosimilars are available in Europe. Rituximab (Rituxan) is another one that's come off patent [and there are biosimilars for it].
Think of all those other antibodies we're using now. All of those checkpoint inhibitors, other HER2-targeted antibodies, and antibody-drug conjugates. We need to be comfortable with biosimilars because we're just starting [with them], and we've got a lot of other agents that are going to meet this biosimilar category in the near future.