Overview of Biosimilars and the Approval Process in Ophthalmology


Rishi P. Singh, MD, and Michael A. Klufas, MD, provide an overview of the significance of and need for biosimilars in the ophthalmology space, and review the approval pathway for biosimilars.

Rishi P. Singh, MD: Hello, and thank you for joining this Peers & Perspectives titled, “Exploring Biosimilars For The Treatment Of Retinal Vascular Diseases.” I’m Dr Rishi Singh, staff physician and president of the Cleveland Clinic Martin Hospital in Cleveland, Florida. And joining me today is Dr Michael Klufas, a retina specialist in Mid Atlantic Retina, Wills Eye Hospital, and assistant professor of ophthalmology at [Sidney Kimmel Medical College of] Thomas Jefferson University in Philadelphia, Pennsylvania. Thank you, Michael, for joining.

Michael A. Klufas, MD: Thanks for having me, Rishi, and [it’s] a really timely topic here to discuss in 2023 and 2024 with biosimilars.

Rishi P. Singh, MD: Great, and in this program, we’re going to discuss the biosimilar approval process, review some of the currently available anti-VEGF biosimilars, and share some practical considerations in adopting biosimilars for the treatment of retinal diseases. Thank you so much for joining, Michael, and let’s begin. So, Michael, what are biosimilars? Why are they significant? And why do we need to know about them as both patients and as retina specialists?

Michael A. Klufas, MD: Great question. And obviously, in the US market, biosimilars are a new type of biologic, at least in ophthalmology, although they have been around for a couple of years in the rheumatology and oncology space. But to just get back to the basics, a biosimilar is a biologic product that’s highly similar to an FDA-approved reference biologic product. They have no clinically meaningful differences from existing reference products, and they do not increase risk in terms of safety or a reduction in efficacy when substituted for the reference product. I always tell my patients, “This is not a generic medication. It’s actually the exact same chemical compound.” …Sometimes patients equate this with a generic drug, and it’s actually not that per the FDA and the science behind them.

Rishi P. Singh, MD: Yes, and…that’s such an important point because it’s not a generic, No. 1. No. 2, this has to go through some different studies and designs of those studies in order for it to get approved. And we already know how much biosimilars have come into the market, really improved access to care. Just looking at some of the other spaces in medicine like rheumatology and cancer, biosimilars have really improved the ability for access to care in those areas. You mentioned the approval process, Michael, and I’d like you to talk a little bit about the differences in the approval processes between the reference product and the biosimilar approval process.

Michael A. Klufas, MD: Yes, of course. We are really familiar with some new compounds or the reference products that we are familiar with. They go through major phase 1,

phase 2, and eventually phase 3 studies. And basically, the goal of those studies is to establish de novo safety and efficacy of a new product. Biosimilars go through a similar process,

but it’s a little bit of a different pathway. It’s known as an abbreviated 351(k) BLA [biologics license application]. And the goal of these studies is to demonstrate biosimilarity and sometimes interchangeability to our reference product based on comparative assessments. And what are these comparative assessments? We look at [data from] comparative clinical studies, comparative clinical pharmacologic studies, nonclinical studies, and also analytic studies of these biosimilar products to create a totality of evidence that this product is no different than the reference product in terms of safety and efficacy clinically.

Rishi P. Singh, MD: Yes, and I think it’s so important to tell people that this is not a product that comes to market without a lot of demonstrations. The first demonstration is around, as you said, the analytical trials, or the pharmacokinetics are done in the lab. Obviously, [this includes] the animal toxicology studies which are done with all products and then the clinical studies which are hastened as a result and then make it significantly less expensive to conduct those clinical trials because it can be much smaller in nature. And I agree with you that…a lot of these are obviously much slimmer pathways to approval rather than [the] reference product in general. When you look at this reference product, you look at a biosimilar, how do we explore the efficacy and the safety and how [is] that done in a clinical study for these product trainings.

Michael A. Klufas, MD: Yes, great question. You know, we can talk about 1 of the major studies for a ranibizumab biosimilar that was known as the COLUMBUS-AMD study. There were several hundred patients in this study; after all the preclinical and toxicity and in lab studies are done, they move on to a clinical study. So, for instance, in the COLUMBUS-AMD trial, it was a head-to-head study that established the clinical equivalence of a ranibizumab biosimilar to reference ranibizumab, and patients were [randomly assigned] 1 to 1. There [was] a total of 477 patients in the study: 238 in the biosimilar arm and about 239 in the reference product arm. And they look at the best corrected visual acuity at week 8, as well as numerous other secondary outcomes we may be familiar with from a reference product trial, such as the change in best corrected visual acuity from baseline, as well as anatomic OCT [optical coherence tomography] data. They also look at safety, similar safety standpoint, such as endophthalmitis and immunogenicity, whether that’s neutralizing antibodies or antidrug antibodies. So it’s a pretty robust clinical trial, but it does go straight toward a…phase 3–type equivalence trial for a ranibizumab biosimilar at this time.

Rishi P. Singh, MD: Yes, that’s great. Now that encapsulates what kind of study is done.

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

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