The Use of Biosimilars in Oncology

Host Dr. John Sweetenham, associate director of Clinical Affairs at the UT Southwestern Harold C. Simmons Comprehensive Cancer Center, and Dr. Zeina Nahleh, breast cancer medical oncologist and regional chair of the Cleveland Clinic Florida Cancer Institute, discuss the new ASCO Expert Panel report on the use of biosimilars in oncology, and their potential as an affordable, effective alternative for cancer care.   Transcript Dr. John Sweetenham: Hello, I'm John Sweetenham the associate director for clinical affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and host of the ASCO Daily News podcast. Today, we'll be discussing the use of biosimilars in oncology. These are licensed biological products that are largely analogous to the U.S. Food and Drug Administration (FDA)-approved originator or reference products, and a recent report from an ASCO Expert Panel found that biosimilars may be an affordable and effective alternative to their reference of biological product for cancer care.   Dr. Zeina Nahleh, was the co-chair of the Expert Panel that clarified the potential value and utility of biosimilars in oncology. I'm delighted to welcome her to the podcast today. Dr. Nahleh is a breast cancer medical oncologist who serves as the regional chair of the Cleveland Clinic Florida Cancer Institute.   My guest and I have no conflicts relating to our topic today. Our full disclosures are available in the show notes and disclosures of all guests on the podcast can be found in our transcripts at asco.org/podcasts. Dr. Nahleh, many thanks for being on the podcast today.   Dr. Zeina Nahleh: It's a great pleasure to be here.   Dr. John Sweetenham: Dr. Nahleh, oncology-related biosimilars were first approved by the FDA back in 2015. Could you open up by maybe giving us an explanation of exactly what biosimilars are and how these agents are currently being used specifically in oncology?   Dr. Zeina Nahleh: Biosimilars for oncology were developed for 2 purposes, basically: to hopefully decrease the overall costs of care, [and] to improve access to cancer therapies. The FDA has a clear definition of a biosimilar. It is a similar, but not identical to an already licensed biologic product. That's really the definition – it's similar in terms of quality, safety, and efficacy.   Now, biosimilars are produced in living cells. They are purified. They go through multi-step processes, so they're not really identical to the original product, but they're very similar. The use of biosimilars, as you mentioned, it started in 2015 as an unauthorized oncology product, and the FDA has since approved several biosimilar products. And the process to authorize this product goes through a lot of rigorous processes really of checks and balances, but they are really supposed to be equivalent in terms of safety and efficacy and not meaningfully different from the original reference product.   Dr. John Sweetenham: Thank you. One thing I should have mentioned right up front and apologize for not doing so is that I would certainly recommend that all our listeners take a look at the report that you co-authored with the other members of the panel because I think number 1, it's extremely informative in many domains, but I think it really gives an excellent description of the development process [of] biosimilars and [the] approval process, which is currently I think, relatively poorly understood.   On that theme, I think as a member of the panel, your panel report noted that there was a lack of clinician understanding about biosimilars and their utility. I think that's been reflected in the fact that the uptake of biosimilars in the oncology committee has been relatively slow. I think you probably agree with that. What do you think are the major barriers to biosimilar use that you found as you reviewed the literature? When do you think they are an acceptable alternative to the available reference biologics?   Dr. Zeina Nahleh: There are some barriers for clinicians to utilize biosimilars. For example, it could be a lack of fully understanding the way biosimilars are produced, whether they're safe because their development is not exactly the same. Sometimes they're confused with generic drugs, and they are not generic at all, they are completely different. Some other barriers would be mostly the efficacy because they haven't been, or the thought is that they are not compared head-to-head to a reference product, which is a normal way of identifying new cancer or oncology medications—to go through the phase 3 clinical trials and the usual process for research.   That's a little bit different from the way they approve biosimilars. It could be perceived that there is some inadequate evidence supporting these biosimilars. There are a lot of misbeliefs that I believe underscore the need for more education. It's great, John, that you're doing this podcast to clarify some of these questions.   Dr. John Sweetenham: Yes. In fact, although I don't think it's been absolutely definitely determined for most of the biosimilars, but I do think it's right to say that there are some signals that 1 or 2 of the biosimilars may even be superior in efficacy, at least in terms of response rates and so on to their originator products. There's been this term around of biobetters. I don't know what the panel's feeling was about that, and whether there is enough of a signal there for us to be thinking very seriously about them being possibly a better alternative to the originator product.   Dr. Zeina Nahleh: Like you mentioned, the manuscript really goes into some details and illustrates how the process has evolved to approve these biosimilars, so it may not be well known, but really the FDA approval process is very rigorous. It requires a lot of clinical and safety data. And many times actually, a request for a biosimilar drug is returned or rejected pending more investigation and more details.   Yes, there are some differences compared to the traditional clinical trial design, but really a lot of information and details go into these approvals, and whether it’s clinical data or safety data or pharmacokinetic, it's really based on robust data. Many times, several clinical trials are required. You're absolutely correct, and we believe strongly as a panel that the biosimilars available in the U.S. are quite safe and effective and therefore ASCO has endorsed the biosimilar use in many of the clinical guidelines.   Dr. John Sweetenham: Right. One of the things I think perhaps we haven't touched on so far is, of course, that for the most part, the biosimilars represent a significant cost saving both for health systems and also hopefully to patients compared with the reference product. That in itself brings me on to what I've perceived as 1 of the issues that perhaps makes clinicians a little bit nervous about the day-to-day use of biosimilars, and that's this concept of interchangeability. Your report certainly advocated for interchangeability. Could you just describe for our listeners what this actually means, this concept of interchangeability and why in the report you certainly address this in a pretty favorable way?   Dr. Zeina Nahleh: Interchangeability has different meanings, but just to make it simple, unless the biosimilar product is designated to be interchangeable, we still recommend that people do not just substitute a biosimilar for a reference product without notifying the prescriber. That's different than the generic. Generic is different where the pharmacist can easily switch between the 2. So far, we are still recommending that the prescribing provider is notified when a pharmacist is recommending changing the prescription to a biosimilar product. Just to clarify also, what's the difference between biosimilar and generic? Because I think sometimes there's some uncertainty here.   Dr. John Sweetenham: Yeah.   Dr. Zeina Nahleh: The generic version of the drug is expected to be identical to the brand name product. They have to be the same. Now, they are manufactured the same way, they're marketed the same way, so they are really the same version of the brand drug. This is different than the biosimilar. The biosimilar is a biologic agent produced by a living system. It's not manufactured the same way. It's actually not likely to be identical to the brand-name product.   This is 1 of the main principal differences between generic drugs and biosimilars is that the manufacturing process uses different production and purification processes. There are some inherent differences between biosimilars and generic drugs. There are some unresolved challenges, and in the U.S. actually, there is no biosimilar that is approved as an interchangeable product. There are some specific guidelines by the FDA for potentially granting the designation of being an interchangeable product.   Several states have put in place some guidelines on this, so it is recommended to review each state-by-state recommendation. But as a whole, we believe that biosimilars can be a safe and effective product, but still, the recommendation of the panel is to communicate with the providing physician if and when a biosimilar is to be replacing the main product, and that's really the recommendation.   So far, we don't recommend using interchangeability without including the prescribing team. Okay, so there are some safety concerns raised, but that's not the issue. The issue is that we believe it is not the same as a generic replacing a brand name—Pharmacy and Therapeutic Committees have to include the prescribing physician into this conversation.   Dr. John Sweetenham: Thanks that does help clarify that. It takes me onto my next question because I think we are getting to this issue of point of care decisions about whether to use a biosimilar and if so, which 1 to use. Of course, there are a couple of drivers of that. One of them is the health system itself and its “P and T” (Pharmacy and Therapeutics) Committee and so on and whether they will approve specific biosimilars.   Then the other issue that comes into play, and we certainly experienced this in our own institution is the 1 of insurance coverage. As I'm sure you know well, different insurance companies have variable policies and preferences about which biosimilars, if any, can be used in their covered patient. And if you are a physician at the point of care, trying to make a biosimilar decision, this makes it complicated because it can frequently lead to denials that can result in delays in treatment while this is figured out.   Could you comment at all on what decision support tools are already out there, or in development for physicians at the point of care to make this an easier process for them and for the patients and to avoid delays in treatment?   Dr. Zeina Nahleh: I have to say that it varies, there is really no standard. Speaking to several colleagues and several institutions, you would hear different responses, but in general, we know that insurance can vary substantially in terms of approving or authorizing certain biosimilars versus others. There was really no standard, and it is clearly important for all of us as clinicians to check with the pharmacy and with the insurance to make sure that we are delivering the treatment that is most appropriate for the patients based on their insurance.   In many cases, the insurance company would dictate sometimes what biosimilar and or what agent they would approve versus another. In this case, sometimes we are obligated to follow what the insurance is recommending in terms of reimbursement. It's a complex challenge, I believe, in health care. I believe it is important, though, to recognize that biosimilars are a safe and effective alternative to the original product, so people should feel comfort in using these agents we have outlined in the paper around 17 oncology FDA-approved biosimilars that have been supported by evidence, and these are very safe to use.   They go from supportive drugs like filgrastim to other products. I think it is important to recognize that the biosimilars are . . . well, first are here to stay and they could contribute, they can improve our care delivery if used appropriately. Now, the question of insurance and the payer, we always have to refer to those to make sure the patient receives the— does not incur extra cost.   Dr. John Sweetenham: Thanks for that great response. You mentioned safety and perhaps it will be worth just returning to that for a moment. Do you think that there are residual safety concerns around the use of biosimilars that we should be worried about? Do you think that we need data that we already have to track and monitor the individual biosimilars in a postmarking environment?   Maybe I'll just add onto that a partially related question, and that is, in your own institution, how have you handled the issue of consent to patients, patient consent to biosimilars, and addressing the issues of safety and efficacy with the patients?   Dr. Zeina Nahleh: I'll start with the consent. We have developed a process where we can write the biological name of the drug, say trastuzumab, and that should cover also the biosimilar version or any other commercial version, so that should be an acceptable way, at least in our institution to do this.   Of course, we educate the patients. Many times, patients expect 1 product and they see another name and we try to educate the patients that these are safe and equivalent products, and you should have no problem. It's a lot of education, a lot of communication with the patients, but we are able to provide the consent forms in that manner to minimize frequent consenting and different—doing it many times.   Now, going back to the issue of safety, like I mentioned initially, so biosimilars have been developed as a safe alternative, and they are approved after a very rigorous review by the FDA, and they have to exhibit no clinically meaningful differences. Many times they're compared to the original product. They look at their safety, their purity, potency, they look at a lot of criteria, both clinical data and pharmacokinetics. It goes through a rigorous process and sometimes it takes years to approve these products.   Again, we recommend that the biosimilars used in the U.S., the FDA-approved biosimilars be adopted because these have been looked at and validated, and they look at their competitive studies, analytical data, pharmacokinetic, so they compare to the original product, but they also make sure that there is really no deviation in terms of quality and safety.   [The] FDA also recognizes some of the uncertainties and therefore they have also requested post-approval monitoring, and that's important to mention because post-market surveillance is included in many of these products. They continue to recommend follow-up on these biosimilars after being approved and in the market. I hope that covers the question.   Dr. John Sweetenham: I think it does. Absolutely. Thank you for that. And I really appreciate your insights. Dr. Nahleh, many thanks for joining us on the podcast today. I'd like to congratulate you and the expert panel for the work that you've done on biosimilars, and for what I think is a great report that really clarifies the use of these agents and hopefully is going to help over time with the adoption of these agents into oncology practice.   I think there are clear benefits in terms of the cost-saving from these agents, both to our systems, but more importantly to our patients. Thank you so much for all of the work you've done, and thanks again for sharing your insights on the use of biosimilars in oncology with us today.   Dr. Zeina Nahleh: Thanks so much, John, for having me. It's great pleasure. Thank you for all you're doing and hope we covered some of these questions. We look forward to more updates from ASCO on biosimilars in the next few months and years to come.   Dr. John Sweetenham: Absolutely. And thank you too, to our listeners for your time today. If you enjoyed this episode, please take a moment to rate and review us wherever you get your podcasts.     Disclosures:  Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness Dr. Zeina Nahleh: None disclosed. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.