Biosimilar Series: Part 3

In this episode, the third of our biosimilar education series, Neil Udovich spoke with Kathy Oubre, CEO of Pontchartrain Cancer Center, about the FDA approval process for biosimilars, the Biologics Price Competition and Innovation Act and safety issues or adverse effects related to biosimilar use.

If you have any questions for today’s guests, or have a topic you would like to hear more about, email OnCall@cencora.com.

Transcript

[00:00:35] Neil: Kathy, last time we talked about biosimilars and what they are and what they aren't biologics generics versus the actual biosimilar. But talk to me about how the FDA approval process works with biosimilars and how that might differ from differ from some of the other, uh, types of therapeutics.

[00:00:56] Kathy: Sure. So, you know, the goal of a biosimilar development program is not to independently establish the safety and efficacy of the biosimilar, but to demonstrate that the proposed biologic product is biosimilar to the reference product.

So consequently, you know, the FDA biosimilar development approach is to identify any differences between the reference product and the biosimilar. And, you know, with the goal there to determine what residual uncertainty about biosimilarity remains, you know, based on potential impact of, you know, observed differences.

So, you know, the design is to really just look at whether there's any differences between the product, but the safety and efficacy has already been established in that reference product. So, you know, to go back for a minute on just biologics as a, you know, as a whole, you know, the FDA holds all biologics reference and biosimilars.

To the same good manufacturing practice standards. And so biosim manufacturers must have the same long term commitment to quality for those biosimilars to proceed. And then we can get a little bit into the science behind it. You know, understanding of biologics immunogenicity profile is very important.

It's key to establishing a biologics safety profile. So in the world of biologics, you know, you'll see head to head assessments, comparing immunogenicity of the biosimilar and the reference product. Um, and it's considered a key component of a biosimilars clinical development program.

So, you know, you know, in addition, you know, there's no single study, that's considered pivotal to a biosimilar application, rather it's the totality of data and information submitted to the FDA to support biosimilarity. While reference products with multiple indications require clinical studies to establish safety and efficacy for each indication.

Biosimilars are not required to be evaluated clinically in every indication held by that reference product for which approval is sought. Instead, a biosimilar manufacturer can extrapolate data and information supporting biosimilarity in one condition to others, for which the reference product is licensed.

And in general, it is likely for a biosimilar to be approved for all of the reference products indications, but not always, you know, but the FDA was also very clear in noting that biosimilarity is not sufficient for interchange. So there's a whole different pathway. If a biosim manufacturer wants to have, you know, interchangeability designation.

So to support interchangeability, the FDA guidance indicates that the manufacturer is expected to conduct one or more switching studies that assess safety and efficacy of alternating between the reference product and the biosim. And currently all 50 states have passed legislation to allow a pharmacist, to substitute a biosimilar for the reference product with prescriber approval and that was as of July, 2021.

[00:04:41]Neil: And I'm assuming, is that assuming that those biosimilars have done the interchangeability studies before that? Okay.

[00:04:51]Kathy: Mm-hmm  and again, you know, you have to remember you. For that particular thing, you know, in regards to the legislation, we're typically talking about part D products D as in dog, um, you know, obviously not part B.

[00:05:07] Neil: Got it. That was great. That second bit, I, I actually learned something I didn't realize. How do you know if a drug has that interchangeability study and the ability to be interchangeable cause it'll be in their indication that I manage that.

[00:05:22] Kathy: Well, you know, Semglee is currently, you know, one of the only, you know, I, they did this, but there's really not a lot of biosimilars that can be interchanged right now on you at your CVS or Walgreens by a pharmacist? I think they were looking at the road ahead.

[00:05:47] Neil: Well, but like would, would the peg did the, Pegfilgrastim go through that interchangeability studies?

[00:05:54] Kathy: They didn't have to. No. Well, I mean, but that's a part B drug.

[00:05:59] Neil: Okay.  Got it. Thank you. Well, so when I read or I hear about FDA approvals, I read about something called BPCIA. What is that?

[00:06:12] Kathy: Yeah. So, you know, we'll talk about, let's talk about BPCIA, it doesn't roll off the tongue for me either and its impact on FDA approval. So the biologics price competition and innovation act was established in 2010 to, create an abbreviated pathway approval pathway for biosimilars in the US. And because biologics and biosimilars are made from living cells, the development process is much more complex than it is for generics, which are chemically synthesized, small molecules.

And interestingly, you know, a biosimilar requires the creation of a new manufacturing process and custom cell line. Since the reference products, manufacturing process is proprietary and not publicly available. Neil. That's really all it is.

[00:07:10] Neil: That's all it is. What are some of the safety issues or adverse effects related to biosimilar use? If any?

[00:07:15] Kathy: Well, so, you know, because biosimilars are highly similar to the reference product, there should be no specific safety issues or adverse events. Seen in a biosimilar versus the existing profile of the reference product.

You know, again, there shouldn't be, there may be, you know, as of February 22nd, 2022, you know, the FDA though had not had any reported, you know, safety issues are adverse events, but you know, communicated to them by physicians, you know, community practice seen in their patients as a result of biosimilar usage.

You know, but again, you know, all biologics, including biosimilars have the potential to induce an unwanted immune response. And, you know, the impact of that immune response, which is called immunogenicity can range from no apparent effect to changes in pharmacokinetics, which would be loss of effect or a serious adverse effect.

[00:08:23] Neil: Just speaking from your experience in the practice and the physicians in your practice and those others in the community, then, you know, we talked about 80% biosimilar market share,  uptake within community practices. I would imagine that that speaks very highly to how physicians view the safety and efficacy of these products.

[00:08:42] Kathy: I think so. I mean, you know, in the very beginning, Community oncology, you know, because that's the lens that, you know, I work in, you know, we were a little concerned, you know, but we had the luxury of being able to see these drugs function in the EU for almost a decade. So even though we were, you know, a little concerned and you might start it with new patients, we certainly had a higher comfort level when you know, biosimilars Pegfilgrastim and then the therapeutic agents were available.

[00:09:20] Neil: Well, thank you again for your thoughts and insights on the topic.

[00:09:23] Kathy: Yep. You're welcome