Allan Gibofsky, MD: What are the physical differences between a biosimilar and a generic?
Gary R. Lichtenstein, MD: To start, there are different ways that they’re made. Biosimilars are made in host cell lines, whereas the generics are small molecules.
Peter L. Salgo, MD: OK. So one is alive, one isn’t?
Gary R. Lichtenstein, MD: Correct.
Peter L. Salgo, MD: That’s a huge difference, right?
Gary R. Lichtenstein, MD: Exactly.
Peter L. Salgo, MD: It’s not “I know where this carbon goes and where this oxygen should be,” it’s “I’m going to grow this, and it should work the same.” Right?
Allan Gibofsky, MD: Well, yes and no. I’m sure what will develop in a few minutes is that the primary structure, the sequencing of the amino acids, has to be the same for a biosimilar and for a bio-originator.
Peter L. Salgo, MD: That’s important.
Allan Gibofsky, MD: Yes.
Peter L. Salgo, MD: That’s good.
Gary R. Lichtenstein, MD: It’s the tertiary structure, the afucosylation, and all different variations which may occur. It’s a different chemical overall tertiary structure that makes a difference.
Peter L. Salgo, MD: And I think you said that they were grown, not manufactured?
Vibeke Strand, MD: That’s where a lot of the variability can occur. So, during the manufacturing process (when the cells are making the product), we get changes to the secondary, tertiary, and even the quaternary structure. Now, those changes have to be very, very small, so that, in fact, the biosimilar will behave exactly like or highly similar to the reference product. We’ve learned a lot about this because we’ve learned so much about manufacturing biologics over the last 30 years. And thus, we can control for these things. But, more importantly, we can actually test for the variability to assess that any of the variability that occurs doesn’t change how the product actually behaves.
Peter L. Salgo, MD: I have this image based on what you said: that when the cells don’t listen to what you tell them, they’re going to do what they want to do.
Vibeke Strand, MD: That’s true.
Peter L. Salgo, MD: And the trick is to make the cells do enough to make this behave well. Is that fair?
Vibeke Strand, MD: That’s fair. And the other process is that manufacturing these products has improved so much in the last 20 to 30 years with much better scale at much more efficiency of production. All that technology has now allowed us to reverse engineer these products.
Peter L. Salgo, MD: We’ve also got the issue of stability.
Vibeke Strand, MD: Right.
Peter L. Salgo, MD: These are biologicals. These are not pills that you put, I hesitate to say, in the medicine cabinet in your bathroom (because you shouldn’t put pills there). They’re different. They’re not as stable, are they?
Allan Gibofsky, MD: No, they’re not. They can be or they might not be, depending upon the molecule.
Peter L. Salgo, MD: Well, there’s a definitive statement there.
Allan Gibofsky, MD: Well, yes. It depends on the molecule that we’re talking about. But the working definition is that there can be differences in the molecule between a biosimilar and a bio-originator (the reference molecule), but they can’t be clinically meaningful. They can’t affect the safety. They can’t affect the efficacy. They can’t affect the purity or the potency of the molecule that we’re dealing with.
Peter L. Salgo, MD: So, we’re focusing on end effect, as opposed to absolute mirrored structure.
Vibeke Strand, MD: Right.
Allan Gibofsky, MD: Right.
Vibeke Strand, MD: Exactly.
Peter L. Salgo, MD: What are we dealing with in terms of immunogenicity potential?
Vibeke Strand, MD: Essentially, chemical products really have very little, if any, immunogenicity, but all biologics are immunogenic, and they’re different in different people. What’s been interesting about the biosimilar process is that we’ve actually learned a lot more about immunogenicity of both the biosimilar and the reference product because the assays that we’re using now to detect immunogenicity are much more sensitive. They’re much more modern.
Peter L. Salgo, MD: So, the bar is actually higher?
Vibeke Strand, MD: Yes, it is.
Peter L. Salgo, MD: We can examine things in more detail.
IQVIA Highlights Opportunity to Cash In on Biosimilars for Biologics Losing Market Exclusivity
November 29th 2023A report from IQVIA noted that Europe could miss out on €15 billion in cost savings by not having biosimilars for medications about to lose market exclusivity, shedding light on the implications for overall health care savings and ultimately, patient access.
Biosimilar Business Roundup for October 2023—Podcast Edition
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CVS Caremark Switches Up Biosimilar Coverage in 2024
November 27th 2023As new biosimilars are added to CVS Caremark’s standard formulary, others are removed. One notable change is with the Humira biosimilars: the pharmacy benefit manager has removed Amjevita in favor of Hyrimoz and an unbranded biosimilar.
Dr Fran Gregory Sizes Up the US Adalimumab Market: Will Biosimilars See Success?
September 17th 2023On this episode of Not So Different, Fran Gregory, PharmD, MBA, vice president of emerging therapies at Cardinal Health, analyzes the adalimumab market so far in the United States and provides insight into how the market needs to adapt to accept these products and ensure lower drug costs for patients.
Eye on Pharma: Adalimumab Updates; New Eylea Biosimilar Lawsuit; Canada Gains Stelara Biosimilar
November 22nd 2023Several companies make moves to further their adalimumab biosimilars, Regeneron sues Celltrion over biosimilar for Eylea (aflibercept), and Health Canada grants marketing authorization for biosimilar referencing Stelara (ustekinumab).