Biosimilars is a biologic medication that is highly similar to an already approved reference product. It has no clinically meaningful differences in terms of safety, purity, and potency compared to the reference product. As lower-priced versions of originator biologics, biosimilars can offer patients more affordable options. However, regulatory approval hurdles, patent disputes and reimbursement barriers have impeded patient access in the United States.

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The Food and Drug Administration Commissioner Marty Makary announced last week that his agency will expedite the biosimilar approval process by eliminating what he called “unnecessary red tape,” helping to speed lower-cost treatments to market. But in the United States, the greater impediments to patient access to biosimilars have been lengthy patent disputes and reimbursement hurdles.

Makary seeks to replace clinical trial requirements for biosimilar marketing authorization with improved analytical testing in most circumstances. At the same time, the commissioner wants to facilitate pharmacy substitution of biosimilars. In particular, he says that “every biosimilar should be interchangeable” without any “switching studies,” analogous to small molecule generics. This would allow pharmacists to more easily substitute biosimilars for originator biologics. Both the Secretary of Health and Human Services, Robert F. Kennedy Jr., and Makary asserted that such studies are superfluous in all circumstances. Notably, the FDA’s new draft guidance follows what the European regulatory agency has been doing for nearly two decades, namely not requiring demonstration of interchangeability once biosimilarity is established.

Biologics are among the most expensive pharmaceuticals, but some of the early market entrants began to lose their exclusivity rights over the past decade and a half, with many more to do so in the coming years. Biosimilars are versions of branded biologic products that can be manufactured and sold, theoretically once the originator’s patent has expired. Currently, the FDA approves biosimilars based on trials showing that they are “highly similar” to their reference branded biologic. There are no clinically meaningful differences between the originator and biosimilar in terms of safety and effectiveness. Y

Biosimilars offer clinically effective treatment alternatives to branded reference biologic drugs at a lower cost and across a wide range of therapeutic classes, including among others, cancer, autoimmune conditions and insulins. These products are making inroads in the U.S., though market entry and uptake still consistently lag behind Europe. Specifically, biosimilars face challenges unique to the American healthcare ecosystem, including persistent and lengthy patent litigation battles and dynamics in the payer or pharmacy benefit manager space which can impede biosimilar entry altogether or don’t favor adoption of the lower-priced products.

In a Fact Sheet posted Oct. 29, in addition to calling for new guidance that would facilitate biosimilar approvals, the FDA cites the problem of limited access to affordable biologic treatments, which the agency attributes to insufficient market competition and barriers to biosimilar market entry.

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Indeed, for biosimilar manufacturers, getting approval from the FDA is half the battle. Once authorized for marketing, it’s no guarantee that launch will soon follow. Patent litigation initiated by companies producing originator biologics often prevents licensed biosimilars from launching at or near their approval date.

Examples Of Delay In Patient Access To Biosimilars

According to Pharmaceutical Technology, the primary reason for delayed market entry in the U.S. concerns protracted patent disputes, in stark contrast to Europe where such battles are much less common. Sometimes patent settlements involve agreements between originator biologic and biosimilar manufacturers to defer market entry. In addition, biosimilar manufacturers may have to pay originator sponsors a royalty upon launch. Other times, there is no pending agreement, and litigation can drag on for years before there is any deal.

A poster child example of a very lengthy monopoly is the arthritis drug Enbrel (etanercept), which was first approved by the FDA in 1998, and still has no biosimilar on the market in the U.S. As a result of numerous patent filings and subsequent litigation there won’t be biosimilar competition in the U.S. until 2029, despite there being two approved biosimilars: Erelzi in 2016 and Eticovo in 2019. The maker of Enbrel has filed numerous patent applications since the drug came to market 27 years ago.

Meanwhile, since 2016 Enbrel has faced biosimilar competition in Europe. By 2020, across the European continent and the British Isles, the average market share of the first launched Enbrel-referenced biosimilar, Benapali, was 36%, ranging from 14% in Austria to 74% in the United Kingdom. And the average market share of the second biosimilar was 15%. Overall, the level of biosimilar penetration for etanercept was 61% in Germany in 2019.

An originator biologic, Neupogen (filgrastim), used to treat neutropenia (abnormally low count of white blood cells named neutrophils) in cancer patients, faced biosimilar competition in Europe as early as 2008, seven years before the U.S. Prior to the launch of the first Neupogen-referenced biosimilar in the U.S. in 2015, average utilization in Europe of biosimilars in the class was already around 50% with a 40% discount in price.

Humira (adalimumab), a biologic used to treat rheumatoid arthritis and other autoimmune conditions, faced biosimilar competition in Europe by 2018, five years before the U.S. While several Humira-referenced biosimilars were approved in the U.S. in the mid to late 2010s, they couldn’t launch then because of patent litigation. The parties to the lawsuits agreed to delay the launch of approved products until 2023.

By contrast, soon after Humira’s patent expiration, Humira-referenced biosimilars entered European markets, bringing brought about steep discounts in price and substantial cost savings. For example, the price of adalimumab products in Denmark decreased by 82% from September 2018 to December 2018. By 2019, the average market share across Europe of Humira-referenced biosimilars was already around 35%.

Conspicuously, Makary cited the Humira example when alluding to patent issues as a barrier to market competition:* *“We can create more intense competition and let market forces do their work. When Humira had its biosimilar come out seven years later, it should have been closer to two years—or even one year, as we often see in Europe. When there’s that kind of gap, it means a longer period with no competition and higher prices.“

But it takes more than just resolution of patent issues to smooth the path for biosimilar market entry, as the Humira saga illustrates. In the U.S., ten Humira-referenced biosimilars are now on the market, nine of which launched in 2023. At the beginning of 2024, however, biosimilars’ market share was hovering around a measly 2%. The situation changed last year when the pharmacy benefit manager CVS Caremark altered its formulary. The PBM removed the originator Humira from its template formulary for new patient starts. Nevertheless, instead of opening up the therapeutic class to all the marketed biosimilars, CVS Caremark excluded most and included two manufactured by CVS-owned Cordavis, which were not the lowest-priced products.

The problems FDA is addressing related to regulatory approval are real. Juliana Reed, executive director of the Biosimilars Forum, noted that 118 reference biologics are set to lose patent protection in the next decade, “yet only 10% have biosimilars in development.” What she calls a biosimilar void threatens to leave patients without more affordable options.

But patent abuses and payer pricing and reimbursement hurdles are equally if not more important. To solve the patient and market access problems FDA cites in its Fact Sheet, addressing patent law and payer barriers are critical.

In response to the FDA’s draft guidance, Patients For Affordable Drugs Now Executive Director Merith Basey urged “Congress [to] tackle the patent abuses that allow big drug companies to block competition even after FDA approval.”

Basey added that “while biosimilars have already saved the U.S. healthcare system $56 billion, there is the potential for so much more cost-savings. In fact, biosimilars can save an additional $181 billion in the next five years.”