How Comfortable Are You With Biosimilars?

Biologic medications have revolutionized the treatment of psoriasis, with all sorts of other effects on dermatology, not the least of which has been a dramatic increase in our expectations of the cost of medications. Adalimumab (Humira, AbbVie Inc.) alone is a $14 billion product. Patent lives of these drugs are coming to an end, but because biologics are such large and complex molecules, no one can create exact duplicates. Thus, creating generic “copies” is impossible; biosimilars — drugs designed to be very similar but not identical to the original drug — are coming, hoping to capture a share of this large market.

Just as the development of the first biologics raised questions on how they should be used, the introduction of biosimilars raises new questions. Will doctors be comfortable prescribing a biosimilar that is not identical to the original drug? Will we accept patients being switched from originator to biosimilar without our knowledge? Will we be satisfied if biosimilars are tested in patients with rheumatoid arthritis and not psoriasis? Will we be comfortable with potential differences in immunogenicity, safety and efficacy? Will we be comfortable with the biosimilar using the same generic name that the originator drug uses?

Many doctors would answer “no” across the board. The National Psoriasis Foundation’s Medical Board, devoted to patients’ well-being, made a strong statement in this regard, even recommending that a different generic name should be used and that doctors and patients should be notified if a switch between originator and a biosimilar is made.1 

I do not share these concerns. Sure, I understand that biologics are so complicated that there is no way to make a biosimilar that is identical to the originator molecule. I understand that even small differences, minute differences, can, in theory, make big differences in immunogenicity, safety and efficacy. But I am totally comfortable with biosimilars because biologics can never be duplicated. Biologics cannot even be duplicated from batch to batch by the companies that make the innovator product.

That’s right, our current biologics, drugs like etanercept (Enbrel, Amgen Inc.) are not the same from batch to batch.2 They are not even a single drug entity, with multiple variants within a batch that vary from batch to batch. While studies have demonstrated variation between batches of innovator products, I have not seen any head-to-head studies showing that there are no clinically meaningful differences in immunogenicity, safety and efficacy between these variants. Yet, none of us seem at all uncomfortable with the variation when prescribing today’s biologics (many of us might not have even known about the variation), even though we have far less information on similarity than we will be getting with biosimilars.

When the biosimilars come, we will be given evidence demonstrating that there is remarkable similarity between the biosimilar and the innovator. We will get extensive pre-clinical information that shows the molecular composition and structure, ligand binding, pharmacokinetics and immunogenicity are remarkably similar. While that might be enough to give us a lot of confidence that the biosimilar would act just like the innovator, we will even get data showing the drug works the same in humans with a disease (albeit perhaps not a dermatologic disease). We get none of that information now for the innovator product. While there will be some small residual uncertainty that the differences between the biosimilar and the originator could be clinically meaningful, the uncertainty seems small compared to the uncertainty we should have today about batch-to-batch variation within the innovator products. Given my comfort with the innovator products — which have truly worked wonders for my patients — I look forward to biosimilar adalimumab and other biosimilars with anticipation. 

feldmanDr. Feldman is with the Center for Dermatology Research and the Departments of Dermatology, Pathology and Public Health Sciences at Wake Forest University School of Medicine in Winston-Salem, NC. 

References

1. Biosimilar substitution. National Psoriasis Foundation Medical Board. https://www.psoriasis.org/about-psoriasis/treatments/statement-on-biosimilars. Accessed June 25, 2015. 

2. Schiestl M, Stangler T, Torella C, Cepeljnik T, Toll H, Grau R. Acceptable changes in quality attributes of glycosylated biopharmaceuticals. Nat Biotechnol. 2011;29(4):310-312.