Michael A. Klufas, MD

discuss how to gain both physician and patient trust when it comes to using biosimilars to treat ophthalmologic conditions.

Building Confidence in Biosimilars in Ophthalmology

Talk to me a little bit about physician/patient communication. How do you best talk to your patient? I don’t want to say sell, but I want to say in a nice way, how do you convince your patient that this is the right move for them, and they should make consider this among the therapies they’re getting right now?

 I think every case is a physician-patient relationship. In my experience, typically with intravitreal products, there is some more direct consumer, patient advertising out there, but most of the time, patients are putting their confidence in the physician to choose a product that’s going to improve their vision, hopefully, be clinically efficacious and be safe and cost-conscious as well. So my preference is to have a unlabeled biosimilar rather than an off-label compound like bevacizumab. I just feel there is a little bit more safety there from the studies and from real-world evidence. So I definitely use it in treatment-naive patients, and I tell them, “It’s not a generic, it’s from a different manufacturer, similar, same compound from a preclinical assessment” and all these factors. And usually, patients don’t have much of an issue with a biosimilar. I haven’t encountered a lot of resistance, especially because they may be familiar with generic drugs and I emphasize to them, “This is not a generic, it’s quite a different production process” and go from there, and then we make the decision together.

 I think to your point, having that conversation that this is not off-label, that this is produced in the same production facilities that major branded drugs are approved for and the same quality levels are established there, so there’s no concern. It has been used in thousands of patients prior to use, so it has been very safe and effective, and it would save [money], obviously, if you’re on a primary and secondary insurance plan, sometimes the secondaries don’t always cover everything. This is a way of saving that delta for that as well. So that’s another option too. Lastly, before we close, what advice do you have for physicians, maybe [they haven’t been using biosimilars] in some ways? Obviously, there’s a patient part, [which we] just talked about, but what about for the physician side of it? What’s the confidence they need to incorporate [it] in their practices?

Good question. I think many of these companies do have medical science liaisons. They’re happy to provide you with the major trials. I have looked at all these with SB11, the COLUMBUS-AMD [age-related macular degeneration] [trial], and I think there’s a misperception sometimes that, “Oh, there was a 50-patient study that led to approval.” It’s hundreds of patients. So, I think that’s one thing, looking that the data is good or even monographs provided by the company to show the nearly identical gains in vision and also corresponding OCT [optical coherence tomography] [and] CST [central subfield thickness] outcomes. I think one thing we didn’t talk about is extrapolation. This is one thing that’s a little different with biosimilars. Usually there’s a study done in 1 condition and then by the process of extrapolation, they get approval for all the indications of the reference product. Typically, the studies I’ve seen have been done in neovascular age-related macular degeneration and then by extrapolation, they receive approval for macular edema following RVO [retinal vein occlusion], myopic CNV [choroidal neovascularization], and sometimes a DR [diabetic retinopathy] or a diabetic macular edema. And then I think peer-to-peer exchanges like this are highly helpful. If you have a peer you trust who’s using this product, as with many other things, when we have [adverse] effects and ophthalmology, we’re talking to peers, “How do you manage this, how do you do that?” [If you have a peer] or peer group that’s using biosimilars, I would reach out to them and see what their experience has been from a clinical standpoint and also a reimbursement standpoint and the patient satisfaction standpoint.

That’s great. Good to hear that. I think, again, I would say the same thing with cases. Cases can be very helpful to get the point home. I think obviously aggregate data, big data in this area could be very helpful in explaining the case for biosimilars. It’s very valuable, certainly, to see those that research being performed in these areas. Really great to see that hopefully come into practice soon that we can share those with our providers as well. So great. Well, I want to thank you, Michael, for your excellent conversation [about] biosimilars. I want to thank you all for watching this 

 titled, “Inspiring Biosimilars With Treatment of Retina Vascular Disease.” I hope you found this helpful, where we really explored all aspects of biosimilars, including the approval process, how they get into our hands, how there are benefits to both patient and providers, and how we adopt these into clinical practice to help our patients see better each and every day. Thank you very much for your attention.

Transcript is AI-generated and edited for clarity and readability.

Videos

Rishi P. Singh, MD; and Michael A. Klufas, MD, discuss how to gain both physician and patient trust when it comes to using biosimilars to treat ophthalmologic conditions.

Retina specialists review the current challenges with biosimilars in ophthalmology, commenting on insurance coverage and patient assistance programs

Biosimilars in Ophthalmology: Challenges, Access, and Patient Assistance Programs

 What are the challenges you think are facing ophthalmologists and retina specialist in regard to adopting biosimilars as it stands right now?

 Very good question. I think biosimilars are still pretty new. We’ve heard about them in the meetings maybe for the past 2 to 3 years, but they are here now and out for almost a whole year. I think in retina, especially with vision, we treat a lot of vision-threatening complications, vascular disease; we always have some pause injecting something new into the eye. So I think that first injection is really the biggest barrier for an established retina specialist, especially because we have such products that that are great and work well, and we want to do what’s best for that individual patient in our chair. However, I would say education on biosimilars, as we’re doing here, [and] looking at the data, this is not a study that involved 100 patients, there are 500 patients in the study. They’re looking at drug immunogenicity to show that it actually shows the same response to the reference product. They also look at drug antibodies. All these are very similar and really, at the heart of it, it’s the same amino acid sequence. And ranibizumab is actually like a pretty simple amino acid sequence from the basic scientists I’ve talked to, so it’s probably favorable that we started with something that’s relatively on the easier side to manufacture. But I think once you have that first patient and a good outcome, then you start having confidence in using it more in the future. But that first injection I think is a little bit tough for some established retina specialists.

Yeah, I think you’re right, I think that there’s this wariness. With all the information that’s been out there in the past couple years on various drugs, they’re just a little bit wary about adopting a new drug, and I agree with you. I think these drugs have been shown thus far. There have been some nice studies already done and presented at some of our major meetings, which have shown that thousands of injections of these have been done in practice without any significant intraocular inflammation events or anything else that’s a really major concern. So I’m glad to see that that has come to fruition for those drugs so far. [Let’s talk] a little bit about the insurance coverage. Are you running into any insurance issues? I can tell you a little bit about our practice in Ohio. Our practice in Ohio has recently faced some challenges in regard to using a biosimilar as an option following…ranibizumab and then going through a branded drug. So we had to adopt a biosimilar as a result of that. Are you facing similar challenges in regard to insurance in your area?

 Yes, I think that it’s quite variable with the insurers. Obviously in the neovascular AMD [age-related macular degeneration] population, like a regular Medicare patient, you really have choice to use typically whatever you want, whether that’s off-label bevacizumab, a ranibizumab biosimilar, or another branded medication. For other insurers, yes, one issue we’ve encountered is [that] someone may have been on reference ranibizumab since, say, 2016 for maintenance of age-related macular degeneration…. Now we have a biosimilar, and we’re more than willing to be cost-conscious and switch to that medication. But a lot of insurers have step therapy now, which didn’t exist in 2016, and so they’ll look historically and say, “Well, this patient never received off-label bevacizumab. We’d like you to restart step therapy,” which kind of creates an interesting situation for a patient and physician; should you go back to step therapy and try to get a biosimilar, or should you just continue with the reference product? But I think insurers are not only focused on ophthalmology; they have oncology and rheumatology. So we are a major cost center, but all those details haven’t been figured out. So I see evolving policies over time. And we’ve gone to some insurers and said, “Look, this is an interchangeable product. Can we please use this?” And they said, “Oh, interchangeability, great. Now we understand what the FDA means, and we do approve this.” So some with education [they] will be willing to allow a switch.

I’ll add to that. I think that our biggest challenge in our patient population is retention of them on therapy, right? If we had to look at it, I mean, even if we gave a drug frequently every other month as we were doing kind of in practice right now, the average is around 8 to 9 weeks per retina specialist. As long as it was a low-cost option for our patients, we might actually be able to retain them, albeit that would still give the same durability from the injection profile. And that [would] certainly be a way to improve outcomes overall for our populations. What about patient assistance and reimbursement support programs available for biosimilars? Are you aware of any that are helpful to you or are there things you’re using in your practice right now for others to know about?

 I think the easiest one to tackle is the patient assistance programs. They are essentially equivalent to what you’ve been used to with other manufacturers. Many of these manufacturers contribute to different funds that allow patients who meet financial need to have assistance if needed or if they’re uninsured. These programs are very similar in some cases, [offering] even less of a co-pay for patients. So I’ve seen very strong support there, and it’s great to have those for our patients to have options. With regard to reimbursement, one interesting thing I’ve seen is, even when the biosimilars first come to market with biologics for intravitreal injection, typically they have a J code. Well, biosimilars have a Q code, and from a billing standpoint, I would say we’ve had some of the highest confidence.

And the Q codes I think are helpful to us as practices to improve the billing efficiency which we’re used to in the J code model. And I think that will obviously increase the adoption. As you said, like the hesitancy, the adoption had been around that sometimes for that. And we know that the reimbursement models are out there now so they can help with that as well. And certainly co-pay assistance and patient assistance, hub services programs that you mentioned before, incredibly valuable chronic disease funds that we tap into sometimes free drugs for those who are in the injured in populations of people adding around the poverty rates can be very helpful too. And they have all those available for all the biosimilars which are out there right now.

Retina specialists review the current challenges with biosimilars in ophthalmology, commenting on insurance coverage and patient assistance programs.

Current Anti-VEGF Biosimilars Approved for Ophthalmologic Conditions

 We have 2 biosimilars now—[with] many more in the making—2 FDA-approved biosimilars. There’s ranibizumab-eqrn or ranibizumab-nuna. Michael, can you compare and contrast their indications as it currently stands a little bit?

 Great question. Perhaps we’ll start with ranibizumab-nuna. This was actually the first ranibizumab produced biosimilar from a company, Biogen, who had experience with biosimilars in the rheumatology and oncology space. This particular biosimilar is approved for age-related macular degeneration and retinal vein occlusion, macular edema following retinal vein occlusion, and myopic choroidal neovascularization. And it’s available in the 0.5 mg dose. Of note, there is not a 0.3 [mg] dose produced from Biogen, and so there is not approval for diabetic macular edema or diabetic retinopathy. The other currently approved biosimilar [of] ranibizumab, ranibizumab-eqrn, this product is approved for the same indications as the other biosimilar, so age-related macular degeneration, macular edema following retinal vein occlusion, myopic choroidal neovascularization as well as diabetic macular edema and diabetic retinopathy. For the diabetic disease, the dose is 0.3 [mg], as we are used to from the reference product. The other big difference is ranibizumab-eqrn has been granted interchangeability from the FDA. So for the reasons we discussed earlier, it may be substituted for the reference product with no difference in safety and clinical efficacy.

 Absolutely, I think that’s a big difference there between the kind of broad indication with ranibizumab-eqrn vs ranibizumab-nuna. While they’re both available to us, they have very different applications or indications right now. Let’s walk through your thought process, and I’ll give you mine, about where you see biosimilars as being valuable for your patient population. So maybe you can give me kind of the ideal patient, is it a treatment-naive patient, is it a patient with high treatment burden, is it a patient prone to nonadherence due to cost? What would be the ideal patient you think in your practice where you’re applying it today?

 It’s a really interesting question and especially how a physician may want to integrate a biosimilar in their practice. So I think there are a couple approaches. I have used both of these biosimilars, and I think the first time you use a new product, you’re [asking] “Is it going to be the same thing?” We’ve seen clinical trials, we’ve seen the safety [indications], but having done thousands of doses now, in my mind personally and based on the data, it acts the same as the reference ranibizumab. So I think if someone is experienced with using ranibizumab in the past, they could definitely try it on a treatment-naive patient and expect to see the same response as they’ve seen with the reference product. And that would probably be a good foray into introducing a biosimilar into your practice. We’re talking about cost, and if someone’s on a reference ranibizumab, they could be substituted to a biosimilar ranibizumab and you could also observe a similar effect there that could probably give you confidence that you’re going to see the same clinical effect in that patient in terms of treatment interval and anatomic outcomes. In terms of difficult to treat patients, we do have other agents available. Ranibizumab is a great compound. It’s probably the least inflammatory compound we have out in the market along with other drugs as well. [With] a difficult-to-treat patient, it’s totally reasonable to try a biosimilar, although sometimes we’re reaching for some other medications because ranibizumab or others have not worked in the past.

 I would agree with you that I think it’s not the high-frequency treatment patient population I’d be giving this to; it’d be the patient who’s doing well on the reference product, right? Who can potentially get a lower cost overall for what we’re delivering to them through that process. And that would be the way I would apply it. I think…treatment-naive patients are fine as much as treatment experienced patients. And certainly that’s an option to start with that drug potentially and save the patient and your practice some cost with the very similar product into the market and what we can hopefully achieve.

Rishi P. Singh, MD; and Michael A. Klufas, MD, provide an overview of the 2 currently available ophthalmology biosimilars, ranibizumab-eqrn and ranibizumab-nuna, as well as discuss which patient populations will benefit from these treatments.

Rishi P. Singh, MD; and Michael A. Klufas, MD, comment on the reasoning behind a shorter primary end point for biosimilar studies.

Rationale for Shorter End Points in Biosimilar Clinical Trials

 We talked a little bit about the COLUMBUS study, and you mentioned, I think interestingly, that this is 1 of the trials which had a very short primary end point. Eight weeks was the primary end point that some of these trials were both best corrected acuity and central subfield thickness. Can you talk a little bit about why that is such a short primary end point? Because we’ve reached the trials that go on for a year or 2, sometimes 3 years, especially for DME [diabetic macular edema] or DR [diabetic retinopathy]. This is very different. Can you explain some of the differences why?

 It’s a really good question. And I think it seems a little foreign to us at first glance. So, to talk in greater detail about the 8-week data point and why it’s so important. The 8-week best corrected visual acuity data point was determined by the FDA as the primary end point. It’s especially sensitive to detect small changes because the rate of improvement for reference ranibizumab is particularly steep in those first 8 weeks. So by evaluating the data in those first 2 time frames, the FDA believes that the odds of seeing a true difference between the efficacy of a biosimilar ranibizumab and the reference ranibizumab, should 1 exist, will be most captured at that 8-week time point.

 And we all know that these responses to anti-VEGF [vascular endothelial growth factor] can happen very rapidly. Like within 7 days, in fact, and some of the ranibizumab early trials, MARINA, ANCHOR, other ones. So we expect to see the same sort of response. We talk about ranibizumab in these studies, in COLUMBUS, and other studies have been completed now where it can be beneficial to see those really short, early changes which occur within that section.

Michael A. Klufas, MD

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