Biosimilars: What’s the buzz?

I’ve been hearing a lot about biosimilars lately. On Twitter, at the ACR conference, from pharmaceutical companies and physicians, they’re popping up more and more. In the United States, they’re just starting to get approval and reach patients, while in Europe, they’re gaining ground and making biologic medications more affordable. But what does it mean if something is a biosimilar? Are they safe and effective, and how available are they?

What are biosimilars?

Many drugs today have both brand-name and generic versions available for use (Advil and Motrin vs. generic ibuprofen, for example). This is because when a drug is first developed, the developer applies for a patent protecting their new creation. It gives them exclusive rights to produce the drug for a set period of time. Once a drug’s patent protections are up, other companies are legally able to produce that drug as well. In the case of most common medications, the process is (relatively) straightforward: the chemical structure of the drug is known, and the generic can be produced using that knowledge. Since companies that produce a generic didn’t have to expend money on research and approval, the price of the drug is lower as a generic.

Biologic medications are a special class of medication that are far more specialized in production and complicated in structure than most drugs. These include drugs like insulin, growth hormones, and cancer and arthritis treatments. Whereas I’ve made aspirin in a university lab course by carefully combining chemicals, biologic drugs are synthesized by living organisms. This method of production is already a barrier to creating a “generic” version of the drug, because other companies don’t have access to the cells that make the brand-name version.

Additionally, the structures of biologics are unimaginably complex. Line drawings of molecules, like you may have seen in chemistry class, are useful for a drug like aspirin, but they would be a nightmarish tangle for something like arthritis drug Humira. Aspirin’s chemical formula is C₉H₈O₄, while Humira’s is C₆₄₂₈H₉₉₁₂N₁₆₉₄O₁₉₈₇S₄₆. Try drawing that one out.

Biosimilars are (basically) the generics of biologic drugs, but they can’t be called that because their structures aren’t exactly the same. When a company makes a biosimilar, they take the consumer biologic and work backward to try to create a product that works the same. Advil and ibuprofen, which aren’t biologics, have the exact same chemical structure for their active ingredient, but Remicade and Inflectra (the biosimilar) have some differences. So what does that mean?

Biosimilar safety and efficacy

In order for biosimilars to be approved in the United States, their makers have to prove that they are as safe and effective as the brand-name biologic. The standards that the FDA uses are that the biosimilar is “highly similar” to and has “no clinically meaningful differences” from the brand-name biologic.

A biosimilar that is highly similar is proved to be substantially similar to the brand-name biologic in structure and function. While there is no benchmark data point that makes two drugs highly similar, purity, chemical formula, and biological effect are taken into account when comparing a biosimilar to the original biologic. Minor differences to structure may be seen in the inactive parts of the biosimilar, which do not impact its effect. That a biosimilar has no clinically meaningful difference from the brand-name biologic means that it is proved to be as safe and effective. This is determined through studies that measure human exposure and response to the biosimilar.

The lower costs of some biosimilars don’t indicate anything about the quality of the product: in fact, in European countries, even brand-name biologics are sold for a fraction of the price of treatment in the United States thanks to the bargaining done by their healthcare systems. For example, a year’s treatment using Cosentyx costs more than $65,000 in the US but would only cost around $15,000 in Italy.

Biosimilars in the US

The hope is that biosimilars will make biologic drugs more affordable and accessible, but they haven’t caught on very well in the United States yet. Currently, the available biosimilars are few, but more will become available in coming years as patents expire for major biologics. (A biosimilar for Humira, the top-selling drug, is expected in 2023.) In addition to getting over resistance from patients and physicians, biosimilars also face opposition from the makers of brand-name biologics.

One strategy drug makers use has been called “exclusionary contracts,” and it blocked Inflectra so effectively that its maker filed a lawsuit against the maker of Remicade. Through the use of rebates and bundling of medications, hospitals and insurers may feel forced to continue with the brand-name biologic. For example, if a healthcare system wants to switch to a biosimilar, the maker of the brand-name biologic may reduce discounts offered on other drugs that are purchased from it. The lawsuit is still pending, but its outcome may mean big changes for the biosimilar market.

Patent litigation is another strategy used by makers of brand-name biologics. Excessive patents protecting biologics and the processes used to make them mean that getting a biosimilar to market is expensive and can be extremely delayed. Just because a biosimilar is approved by the FDA doesn’t mean it’s being sold–two biosimilars for Humira have been approved in the US, but they won’t reach market until 2023 due to settlements with the maker of Humira. Meanwhile, Humira biosimilars are already on the market in Europe. The costs involved also keep some drug companies away from the biosimilar market, which could slow biosimilar development.

Biosimilar success in Europe

Biosimilars have a longer history in Europe. The first biosimilar was approved in Europe in 2006 (growth hormone Omnitrope), but it took until 2015 for one to be approved in the US (cancer drug Zarxio). Without the litigation seen in the US, biosimilars have an easier time reaching the market.

Additionally, European healthcare systems, often administered by governments, have substantial abilities to negotiate with pharmaceutical companies on price, which has resulted in costs of biologic treatment that are much lower than those in the US. Some of these systems may even require patients to switch to the less expensive biosimilar, if it’s medically advisable, which further promotes biosimilar use.

Biosimilars will become more and more of a force in the coming years as more patents expire and more biosimilars are developed. Currently,
paying for a biologic out of pocket in the US is like paying for a private college education every year of your life. Hopefully, in time, patients will start to see the benefits of market competition from biosimilars–because my medication shouldn’t cost as much as my already-overpriced education.

(In truth, I think I’d rather both cost less.)

-Bri

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