The US Food and Drug Administration (FDA) has approved Cyltezo (adalimumab-adbm) as the first interchangeable biosimilar for Humira (adalimumab) for the treatment of several inflammatory conditions. This means AbbVie, maker of the world’s top-selling drug Humira, could be in for some stiff competition.
Boehringer Ingelheim’s Cyltezo has become the second interchangeable biosimilar approved by the FDA, and the first approved interchangeable monoclonal antibody. Cyltezo is a biosimilar to its reference product Humira, and also interchangeable with it, meaning it can be substituted for Humira by a pharmacist without requiring physician approval. In July 2021, the agency approved the first interchangeable biosimilar product, Semglee (insulin glargine-yfgn) for the treatment of diabetes. Semglee is both biosimilar to, and interchangeable with, Lantus (insulin glargine).
The FDA approved the supplemental Biologics License Application (sBLA) for Cyltezo as the first interchangeable biosimilar with Humira. Cyltezo first received FDA approval in 2017 for the treatment of multiple chronic inflammatory diseases, including moderate to severe rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, as well as moderate to severe Crohn’s disease, ulcerative colitis and chronic plaque psoriasis. The new approval now designates it as interchangeable across all of these indications.
Selling Humira at an inflated list price of $2,400 per dose and battling accusations of patent abuses to prevent biosimilar competition, AbbVie has been facing intense scrutiny and legal troubles over creating a market monopoly with Humira.
Industry analysts like Ronny Gal of Bernstein said the FDA approval of Cyltezo not only has significance for the Humira biosimilar market, but it’s a “landmark achievement” for the whole field because it’s the first interchangeable monoclonal antibody; most biosimilars are monoclonal antibodies.
Boehringer won’t be able to launch its product until July 1, 2023 due to its patent settlement with AbbVie.
The FDA has approved 31 biosimilar products in total, which includes two interchangeable products. Humira biosimilars are highly anticipated as it would offer patients a less expensive alternative to the pricey AbbVie drug.
Cyltezo is administered as a subcutaneous injection.
What’s the Difference Between Biosimilars and Interchangeables?
Interchangeables are a type of biosimilar. All interchangeables are biosimilars, but not all biosimilars are interchangeables. The key to interchangeables is that they can substitute for a reference product without the need for a prescription.
Approval-wise, they have additional requirements as per the Biologics Price Competition and Innovation Act. These include being able to demonstrate that the interchangeable product can generate the same clinical effect as the reference product in any patient. Additional safety and efficacy evaluations may also be involved if the interchangeable is given to a patient on more than one occasion and repeatedly swapped with the reference product.
Cyltezo and the Emerging Humira Biosimilars Market
In 2016, Amgen’s Amjevita became the first adalimumab biosimilar approved by the FDA. After a dispute over alleged patent violations, Amgen entered a deal with the company that granted it the right to launch the biosimilar in Europe in 2018 and in the US in January 2023. Meanwhile, Icelandic company Alvotech recently took AbbVie to court in attempts to break its market monopoly as it plans to launch its adalimumab biosimilar.
Humira brought in more than $16 billion in revenue in the US last year. Boehringer won’t be alone in the lucrative Humira biosimilars market. Along with Amgen, Merck is also set to launch its Humira biosimilar in 2023 as per its commercialization agreement with AbbVie.
What’s the Difference Between Biosimilars and Generics?
Biosimilars are sometimes mistakenly likened to generics, but the two are not the same. A biosimilar is a biological product that is “highly similar” to a reference product that already has FDA approval, and that should have no “clinically meaningful difference” to it.
Whereas generics are synthetic copies designed to be identical to the reference product, biosimilars are modeled after the reference product using biological components, such as living cells and are hence not identical. As such, biosimilars are molecularly more complex and larger than generics, making them more expensive and complicated to develop and manufacture.
Developing generics, on the other hand, is cheaper with shorter timelines because the composition of the drug is already approved and, therefore, less time is spent on research and development. Generics have the same active ingredient and may vary with respect to excipients, which would be similar in nature to those in the reference product.
As such, pathways to approve generics are also shorter than biosimilars, which are approved by the FDA through its biosimilar and interchangeable approval pathway which involves “rigorous approval standards.” The shorter approval time for generics along with the shorter time for development make the cost to consumers significantly lower than branded drugs.