As of today, July 1, Cyltezo (adalimumab-adbm) is commercially available in the United States. It is the first and, to date, only therapeutically interchangeable Humira-related biosimilar to be approved by the Food and Drug Administration (FDA).
A distinctive feature of the US market, the lack of a therapeutic interchangeability label is seen as a significant impediment to physician and patient confidence in biosimilars. As such, Cyltezo could gain a significant marketing advantage over other Humira-branded biosimilars such as Amjevita and the soon-to-be-launched Yusimry.
Five other Humira biosimilars are expected to launch this month alongside Cyltezo. But none of the others have a classification of therapeutic substitutability.
The original monoclonal antibody Humira (adalimumab) is used to treat several autoimmune and inflammatory diseases, including rheumatoid arthritis, Crohn’s disease and ulcerative colitis, among others. Humira was a major blockbuster and, up until this year, has held up against biosimilar competition, despite the fact that there have been more than half a dozen FDA-approved biosimilars since 2017. Unlike the European market – where biosimilars started appearing in 2018 – in the US Humira kept its monopoly until 2023 due to a lengthy court case.
In Europe, Humira-related biosimilars have been on the market for almost five years and have performed very well in terms of uptake. They quickly captured Humira’s market share and indeed achieved dominant positions in many jurisdictions. Biosimilars have done so without there being an official regulatory classification of therapeutic interchangeability in Europe or the UK
Therapeutic interchangeability as a separate FDA approval designation for biosimilars is unique in the United States, along with proof of biosimilarity. For example, the European Medicines Agency does not have such a classification.
Biosimilarity demonstrates that there are no clinically meaningful differences between the safety and efficacy profile of an original biologic and its referenced biosimilar. In order to receive a therapeutic interchangeability designation from the FDA in the US, the biosimilar sponsor must submit additional data from a conversion study.
A biosimilar can replace the reference product at the pharmacy without the intervention of the prescribing healthcare provider – similar to how small molecule generics routinely replace branded drugs.only if the FDA deems it therapeutically interchangeable.
In Europe, on the other hand, every approved biosimilar is considered interchangeable. There are no exchange studies available.
The additional layer of regulation in the US could result in US physicians being reluctant to prescribe biosimilars that have not undergone a conversion study.
A recent survey by AmerisourceBergen also shows that interchangeability is an important factor in US payers’ decisions about biosimilar coverage. “When it comes to adoption, interchangeability is reportedly the key factor, even more so than first-to-market.”
Pharmacy benefit manager Optum Rx has added Cyltezo to its formula alongside two other biosimilars. You will be formally equal with the originator Humira. It is striking that biosimilars are not given a preferential positioning over Humira. At first glance, a cheaper biosimilar should be preferred to a more expensive original product. The corresponding formula status may have to do with rebate deals Humira’s manufacturer AbbVie has with Optum Rx.
In the US, rebates may help sustain the suboptimal biosimilars market. For example, in January, Amjevita (adalimumab-Atto) was launched as the first Humira-related biosimilar in the US. Sponsor Amgen launched both a high list/high discount and a low list/low discount version. Optum Rx decided to include the highest-listed, heavily discounted biosimilar in the formula and exclude the lower-cost version.
All other things being equal, Cyltezo could be preferred by physicians and patients over other Humira-related biosimilars due to its position as a therapeutic substitute. And compared to Humira, patient co-insurance may be lower since Cyltezo’s list price is lower than Humira’s. A patient’s co-insurance is calculated based on a percentage of a product’s list price.