Monoclonal Antibody Biosimilars: Examples and Clinical Uses

When you hear the word biosimilar, you might think it’s just a cheaper version of a brand-name drug-like a generic pill. But monoclonal antibody biosimilars are nothing like that. They’re not copies. They’re not duplicates. They’re incredibly complex biological medicines made from living cells, and getting them right takes years of science, thousands of tests, and billions of dollars. And yet, they’re changing how cancer and autoimmune diseases are treated-making life-saving treatments more affordable without sacrificing safety or effectiveness.

What Makes Monoclonal Antibody Biosimilars Different From Generics?

Generics are simple. They’re small molecules-chemical compounds you can synthesize in a lab. Aspirin, metformin, or ibuprofen? Those are generics. You can make them over and over, and every tablet is identical. That’s not possible with monoclonal antibodies.

Monoclonal antibodies are huge proteins. They weigh about 150,000 daltons-over 25 times heavier than insulin and nearly seven times heavier than growth hormone. These proteins are made by living cells-usually Chinese hamster ovary cells in bioreactors. Even tiny changes in temperature, pH, or nutrient mix during production can alter the protein’s shape, folding, or sugar attachments (called glycosylation). These small differences don’t make the drug less effective, but they do mean no two batches are exactly the same-even from the original manufacturer.

That’s why biosimilars aren’t called generics. They’re called biosimilars because they’re highly similar to the original, or reference, product. The FDA and EMA both require proof that there are no clinically meaningful differences in safety, purity, or potency. That means if a patient switches from the brand-name drug to the biosimilar, they shouldn’t feel any difference in how they respond-or how they feel.

How Are Biosimilars Approved?

Getting a monoclonal antibody biosimilar approved isn’t like filing paperwork for a generic. It’s a marathon. Manufacturers must run a full suite of tests:

• Analytical studies: Hundreds of lab tests comparing the biosimilar to the reference product-looking at protein structure, charge variants, glycosylation patterns, and aggregation levels.
• Non-clinical studies: Animal tests to check toxicity and immune response.
• Clinical studies: Usually one or two trials in healthy volunteers or patients, comparing pharmacokinetics (how the body processes the drug) and pharmacodynamics (how the drug affects the body). Sometimes, a comparative efficacy trial is needed, especially if the reference drug is used for multiple conditions.

The goal? To show that any differences are minor and not harmful. The EMA says the most sensitive clinical indication should be used to test for differences. For example, if a drug works for both rheumatoid arthritis and Crohn’s disease, the trial will focus on the one where immune reactions are most likely to show up.

And then there’s the big hurdle: interchangeability. That’s when a pharmacy can switch a patient from the brand to the biosimilar without asking the doctor. Only a few monoclonal antibody biosimilars have reached this level. Celltrion’s Remsima (infliximab) became the first in the U.S. to get interchangeable status in July 2023. That’s a big deal-it means pharmacists can substitute it automatically, just like they do with generic pills.

Approved Monoclonal Antibody Biosimilars and Their Uses

There are now dozens of approved monoclonal antibody biosimilars in the U.S. and Europe. Here are the most important ones, by reference drug:

Bevacizumab (Avastin)

Used to treat colorectal, lung, brain, and kidney cancers by blocking blood vessel growth that feeds tumors. Six biosimilars are approved in the U.S.:

• Mvasi (2017)
• Zirabev (2019)
• Alymsys (2019)
• Vegzelma (2022)
• Avzivi (2023)
• Jobevne (2023)

All have shown equivalent tumor response rates and safety profiles in clinical trials.

Rituximab (Rituxan)

Targets CD20 on B-cells. Used for non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and autoimmune diseases like rheumatoid arthritis and vasculitis. Three U.S. biosimilars:

• Truxima (2018)
• Ruxience (2020)
• Riabni (2020)

A 2022 study in JAMA Oncology tracked 1,247 patients at 15 U.S. cancer centers who switched from Rituxan to Truxima. No drop in response rates. No increase in side effects. And a 28% drop in cost per infusion.

Trastuzumab (Herceptin)

Blocks HER2 receptors in breast and stomach cancers. Six biosimilars are approved in the U.S.:

• Ogivri (2017)
• Herzuma (2018)
• Ontruzant (2019)
• Trazimera (2020)
• Kanjinti (2019)
• Hercessi (2022)

These have become standard of care for HER2-positive patients. In real-world use, they’ve cut treatment costs by 30-40% without increasing infusion reactions or cardiac side effects.

Infliximab (Remicade)

Used for Crohn’s disease, ulcerative colitis, rheumatoid arthritis, and psoriasis. The first monoclonal antibody biosimilar ever approved-in the EU in 2013. In the U.S., Remsima and Inflectra are both approved, and Remsima is now interchangeable. This was a watershed moment: it proved biosimilars could replace one of the most expensive biologics on the market.

Why Are Biosimilars So Important?

The original monoclonal antibody drugs are expensive. Avastin costs $8,000-$10,000 per infusion. Herceptin runs $5,000-$7,000. Rituxan? Around $6,000. That’s not sustainable for patients, insurers, or hospitals.

Biosimilars bring prices down. On average, they launch at 15-35% lower than the reference drug. In markets with multiple biosimilars-like in Europe-prices can drop over 70%. A 2023 report from Evaluate Pharma predicts biosimilar monoclonal antibodies will save the U.S. healthcare system $250 billion between 2023 and 2028. Bevacizumab, trastuzumab, and rituximab biosimilars will make up 78% of those savings.

That’s not just money. It’s access. More patients get treated. More clinics can afford to offer cutting-edge care. More people survive cancer because they didn’t have to choose between rent and chemotherapy.

Challenges and Misconceptions

Despite the data, adoption isn’t automatic. Three big barriers remain:

• Patent lawsuits: Originator companies file an average of 14.7 patent challenges per biosimilar, delaying market entry for years. A 2023 study from UC Hastings found this is the biggest roadblock in the U.S.
• Provider hesitation: A 2022 ASCO survey showed only 58% of oncologists felt “very confident” prescribing biosimilars. Many still think they’re less effective-even though dozens of studies prove otherwise.
• Formulary restrictions: Pharmacy benefit managers (PBMs) sometimes lock out biosimilars unless the brand drug is exhausted first. That’s called “step therapy.” It adds delays and confusion.

There’s also fear around immunogenicity-whether biosimilars cause more immune reactions. The EMA’s 2021 safety report reviewed 1.2 million patient-years of exposure. Only 12 unexpected immune events were found-equivalent to the rate in patients using the original drugs. That’s 0.001%. Not a risk. A coincidence.

What’s Next?

The pipeline is packed. As of September 2023, 37 monoclonal antibody biosimilars were under FDA review. The biggest focus? Adalimumab (Humira) biosimilars-14 candidates are in late-stage trials. The first, Hyrimoz, got approved in September 2023. Humira was the world’s top-selling drug for years. Its biosimilars could save billions more.

Pembrolizumab (Keytruda) biosimilars are also in the works. Keytruda is the backbone of modern immunotherapy for melanoma, lung cancer, and more. When biosimilars arrive, they’ll open access to checkpoint inhibitors for millions more patients.

The EMA plans to release new guidelines in 2024 for even more complex products: bispecific antibodies and antibody-drug conjugates. These are the next frontier. They’re not just antibodies-they’re targeted drug delivery systems. Making biosimilars of these will be harder. But it’s coming.

Final Thoughts

Monoclonal antibody biosimilars aren’t just cheaper versions. They’re a triumph of science, regulation, and patient advocacy. They prove that you can make complex biological drugs more affordable without cutting corners. They’re backed by thousands of tests, millions of patient data points, and decades of research.

If you’re a patient, ask your doctor: Is there a biosimilar option for me? If you’re a provider, educate yourself-there’s no reason to hesitate anymore. And if you’re paying for care, know this: biosimilars aren’t just saving money. They’re saving lives.