Monoclonal Antibody Biosimilars: Examples and Clinical Uses

When you hear the word biosimilar, you might think it’s just another generic drug. But that’s not true. Monoclonal antibody biosimilars aren’t copies in the way aspirin or metformin are. They’re complex biological medicines made from living cells-like tiny protein machines designed to target specific disease signals in your body. And because they’re made from living systems, no two batches are exactly alike. Even the original product has natural variations. That’s why regulators don’t require them to be identical-they just need to be highly similar with no meaningful difference in safety or effectiveness.

What Makes Monoclonal Antibody Biosimilars Different from Generics?

Generics are simple. They’re small molecules, chemically synthesized, and chemically identical to the brand-name version. A generic ibuprofen tablet has the same atoms in the same arrangement as Advil. Biosimilars? They’re proteins. Big ones. Around 150,000 daltons-about 25 times heavier than insulin and over six times heavier than growth hormone. These proteins are folded, modified, and tagged with sugar molecules (glycans) in living cell cultures. Tiny changes in the manufacturing process-temperature, pH, cell line-can alter those sugar patterns. And those changes? They can affect how the drug works in your body.

The FDA and EMA both require biosimilar manufacturers to prove similarity through over 100 analytical tests. These include mass spectrometry to check protein structure, cell-based assays to measure biological activity, and immunogenicity studies to see if your immune system reacts differently. The goal isn’t perfection-it’s confidence. If a biosimilar performs the same way in clinical trials as the original, and shows no unexpected side effects, it gets approved.

Approved Monoclonal Antibody Biosimilars and Their Uses

There are now dozens of approved monoclonal antibody biosimilars in the U.S. and Europe. Most target cancer or autoimmune diseases-conditions that used to cost tens of thousands of dollars per year. Here are the big ones:

• Bevacizumab biosimilars (Avastin): Used for colorectal, lung, ovarian, and brain cancers. Six biosimilars are approved in the U.S., including Mvasi, Zirabev, and Vegzelma. They block VEGF, a protein that feeds tumor blood vessels.
• Rituximab biosimilars (Rituxan): Treats non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis. Truxima, Ruxience, and Riabni are all approved. They target CD20 on B-cells, shutting down abnormal immune activity.
• Trastuzumab biosimilars (Herceptin): For HER2-positive breast and stomach cancers. Six options exist, like Ogivri, Herzuma, and Kanjinti. They lock onto the HER2 receptor and stop cancer cells from growing.
• Infliximab biosimilars (Remicade): Used for Crohn’s disease, ulcerative colitis, and rheumatoid arthritis. Remsima became the first monoclonal antibody biosimilar in the U.S. to get interchangeable status in July 2023-meaning pharmacists can substitute it without a doctor’s note.
• Adalimumab biosimilars (Humira): The most prescribed biologic in the world. Over 14 biosimilars are in development or approved, including Hyrimoz, approved in September 2023. They block TNF-alpha, a key inflammation driver.

These aren’t just theoretical. In real-world use, switching from the original to a biosimilar has shown no drop in effectiveness. A 2022 study in JAMA Oncology tracked 1,247 patients who switched from Rituxan to Truxima. The response rates, side effects, and survival outcomes were statistically identical. The only difference? Cost dropped by 28% per cycle.

Why Cost Savings Matter

Biologics used to be among the most expensive drugs on the market. A year of Herceptin could cost over $70,000. Today, biosimilars sell for 15-35% less. In some cases, competition has driven prices down even further. The U.S. healthcare system could save $250 billion between 2023 and 2028 from monoclonal antibody biosimilars alone, according to Evaluate Pharma. That’s money that can be redirected to other patients, better infrastructure, or lower premiums.

But savings don’t happen automatically. Pharmacy benefit managers (PBMs) often control which drugs get covered. In 2023, 32% of biosimilar launches faced formulary restrictions-meaning insurers didn’t automatically include them. Providers need to actively choose them. And patients need to know they’re safe.

Safety and Immunogenicity: Real Concerns, Real Data

One big fear is immunogenicity-your body making antibodies against the drug. That can make it less effective or cause allergic reactions. The EMA’s 2021 safety report looked at 1.2 million patient-years of exposure to monoclonal antibody biosimilars. Only 12 cases of unexpected immune reactions were found. That’s 0.001%. The same rate was seen with the original products. So no, biosimilars aren’t riskier.

There was one famous case with cetuximab-an original antibody-where some patients had severe allergic reactions. It turned out they had pre-existing antibodies to a sugar molecule (alpha-1,3-galactose) found in the drug. That sugar came from the mouse cells used to make it. Biosimilar manufacturers now avoid those cell lines. They use human or engineered cells instead. The science has gotten smarter.

What’s Coming Next?

The pipeline is packed. As of September 2023, the FDA had 37 monoclonal antibody biosimilars in review. Six are targeting pembrolizumab (Keytruda), a leading immunotherapy for melanoma and lung cancer. If approved, these could bring down costs for checkpoint inhibitors-drugs that have revolutionized cancer care but remain out of reach for many.

Next up are even more complex molecules: bispecific antibodies (which target two proteins at once) and antibody-drug conjugates (antibodies carrying chemo directly to cancer cells). The EMA plans to release new guidelines for these in early 2024. The FDA is already updating its analytical standards, recommending 127 specific tests to map protein structure, charge variants, and glycosylation patterns. This isn’t guesswork anymore-it’s precision science.

Barriers to Widespread Use

Even with proven safety and cost savings, adoption is slow in some places. Why?

• Patent battles: Each biosimilar launch triggers an average of 14.7 patent challenges, according to UC Hastings. These lawsuits can delay market entry by years.
• Provider hesitation: A 2022 ASCO survey found only 58% of oncologists felt very confident prescribing biosimilars. Many still believe they’re "second-rate." But data doesn’t support that.
• Pharmacy confusion: Some pharmacists don’t know they can substitute interchangeable biosimilars without a new prescription. Education is lagging.

Change is happening, but it’s not automatic. Patients need to ask: "Is there a biosimilar for my drug?" Doctors need to feel supported in prescribing them. And insurers need to make them the default option.

Where This Is Headed

By 2027, monoclonal antibody biosimilars could make up 35% of all biologic prescriptions in the U.S., up from 18% in 2022. Cancer therapies will account for 62% of that volume. That means more people will get life-saving treatments-not just those who can afford $100,000-a-year drugs.

The future isn’t about replacing originals. It’s about expanding access. Biosimilars are the bridge between groundbreaking science and real-world affordability. They’re not perfect. But they’re close enough-and that’s enough to save lives.