By 2028, the world’s most profitable cancer drug, Keytruda, will lose its patent protection. That’s not just a milestone-it’s a seismic shift in how millions of patients access life-saving treatments. Keytruda, made by Merck, brought in $25.5 billion in sales in 2024. When biosimilars enter the market, prices could drop by 30% or more. That means more patients get treated, hospitals save money, and insurers pay less. But this isn’t just about one drug. Between 2025 and 2030, over $200 billion in annual global sales from top biologics will open up to competition. This is the biggest wave of biosimilar entry in history.
What Exactly Are Biosimilars?
Biosimilars aren’t generics. Generics are exact copies of small-molecule drugs like aspirin or statins. Biosimilars are copies of complex biologic drugs-medicines made from living cells. Think monoclonal antibodies, vaccines, or proteins that target immune systems. These aren’t made in a chemistry lab. They’re grown in bioreactors, like tiny biological factories. Even tiny changes in temperature, pH, or nutrient mix can alter the final product. That’s why biosimilars must be highly similar to the original, not identical. The FDA requires over 100 analytical tests to prove they work the same way in the body. No clinically meaningful differences in safety or effectiveness. That’s the rule.
Take Humira (adalimumab), the world’s best-selling drug for years. When its patents expired in 2023, 12 biosimilars hit the U.S. market within 18 months. Today, 80% of new prescriptions are for biosimilars. Patients didn’t notice a difference. Their insurance paid less. Hospitals saved millions. That’s the model for what’s coming next.
The Patent Cliff: What’s Expiring and When
The next wave of expirations isn’t random. It’s a calendar of blockbuster drugs. Here’s what’s coming:
- Eylea (aflibercept) - Patent expired in 2025. Used for macular degeneration. Three biosimilars are already on the market, with 12% U.S. market share by Q1 2025.
- Enbrel (etanercept) - Biosimilar launched in 2023 at 35% discount. Now controls over 60% of new prescriptions.
- Cosentyx (secukinumab) - Patent expires in 2029. Samsung Bioepis’ biosimilar got EU approval in late 2025 and is targeting U.S. entry in 2026.
- Keytruda (pembrolizumab) - Patent expires in 2028. Fourteen companies are in late-stage trials. This could be the biggest biosimilar launch ever.
- Eliquis (apixaban) - Patent extended to 2029 thanks to pediatric exclusivity. Still, biosimilars are coming.
These aren’t niche drugs. They treat cancer, arthritis, diabetes, and eye disease. Millions rely on them. And they’re expensive. A year of Keytruda costs over $150,000. A biosimilar version? Maybe $100,000. That’s a 33% drop. Multiply that by hundreds of thousands of patients. The savings add up fast.
Why Biosimilars Are Harder Than Generics
It’s not just about copying a pill. Biologics are living molecules. A single antibody like Keytruda has over 1,000 amino acids folded into a precise 3D shape. Even a single sugar molecule attached differently (called glycosylation) can change how the immune system reacts. That’s why biosimilar makers spend years building specialized manufacturing plants. Samsung Bioepis invested $450 million in a single facility in South Korea just to make sure every batch matches the original.
The FDA requires:
- Over 100 analytical tests comparing molecular structure
- Nonclinical studies in animals
- Pharmacokinetic studies in humans
- One clinical trial proving safety and efficacy
This takes 7-10 years and costs $150-250 million per product. That’s why only big players are doing it: Sandoz, Celltrion, Biocon, Samsung Bioepis. Small startups can’t afford it.
Market Entry: Who’s Winning and How
It’s not enough to get FDA approval. You have to get into hospitals, pharmacies, and insurance plans. And that’s where things get messy.
Here’s how it works:
- Price discount: Most biosimilars launch at 15-35% below the originator. Sandoz’s Enbrel biosimilar started at 35%. Pfizer’s Ibrance biosimilar will launch at 20-25%.
- Substitution rules: Some states allow pharmacists to swap biosimilars without doctor approval. Others require the prescriber to say “dispense as written.” This slows adoption.
- Payer pressure: Medicare Part B reimburses providers based on the drug’s average sales price. If a biosimilar is cheaper, providers earn less. That creates a hidden incentive to keep using the expensive original. Some health systems are fixing this. Kaiser Permanente now mandates biosimilar substitution for all new G-CSF prescriptions.
- Value-based contracts: Sandoz and UnitedHealthcare agreed: if the biosimilar doesn’t save 25%, Sandoz refunds the difference. That’s bold. It shifts risk from insurers to manufacturers.
Europe is ahead. In countries like Germany and Sweden, biosimilar use exceeds 70% for many drugs. The U.S. is catching up. In 2024, the FDA approved 17 new biosimilars-up from just five in 2020. That’s a 240% increase in just four years.
Real-World Challenges: When Biosimilars Don’t Go Smoothly
Not every switch goes well. At the American Society of Clinical Oncology in 2024, Dr. Laura Chow reported excellent results switching rheumatoid arthritis patients from Humira to its biosimilars. No new side effects. No drop in effectiveness.
But Dr. Richard Pazdur from the FDA’s Oncology Center found something else. In a study published in the Journal of Clinical Oncology, some cancer patients had unexpected immune reactions after switching between rituximab biosimilars and the original. It wasn’t common. But it happened. That’s why many oncologists still prefer to keep patients on the same product.
Patients are confused, too. A 2024 survey by the Cancer Support Community found 78% were happy with the lower cost. But 34% didn’t understand why their drug changed. Pharmacists at CVS Caremark saw 22% fewer prior authorization denials for biosimilars in Q2 2025-proof that payers are getting behind them. But academic hospitals still struggle to track long-term outcomes across 10+ versions of the same drug.
The Big Picture: Savings, Strategy, and Future Outlook
The RAND Corporation estimates biosimilars will save the U.S. healthcare system $250 billion over the next decade. The Congressional Budget Office says Medicare alone will save $51 billion between 2026 and 2035. That’s real money. It means more patients get treated. More screenings. More follow-ups.
But originator companies aren’t giving up. Merck has 237 patents around Keytruda, with expirations stretching to 2035. They’re using “product hopping”-slightly reformulating the drug to reset patent clocks. Eliquis was delayed by four years due to patent litigation. That’s the dark side.
Still, the trend is clear. The global biosimilars market hit $12.7 billion in 2024. It’s on track to hit $80 billion by 2030. The U.S. will lead this growth-not because it’s early, but because it’s late. When the floodgates open, demand will explode.
What’s next? More biosimilars for complex drugs like antibody-drug conjugates. FDA’s 2025 draft guidance is already streamlining approvals. Payers are mandating them. Hospitals are updating their systems. The question isn’t whether biosimilars will come. It’s how fast they’ll replace the originals-and how much money they’ll save.
Frequently Asked Questions
Are biosimilars as safe as the original biologics?
Yes. The FDA requires biosimilars to undergo extensive testing to prove they are highly similar to the original drug, with no clinically meaningful differences in safety, purity, or potency. Over 47 biosimilars are already approved in the U.S., and real-world data from Humira biosimilars show no increase in adverse events. However, rare immune reactions have been reported in some cancer patients switching between biosimilar versions, which is why some doctors prefer to keep patients on the same product.
Why are biosimilars cheaper than the original biologics?
Biosimilars don’t need to repeat the full clinical trials that the original drug went through. They rely on the original’s safety data and only need to prove similarity through analytical tests and one small clinical trial. This cuts development costs by 70-80%. Manufacturers also face more competition, which drives prices down. Most launch at 15-35% below the reference product, with prices dropping further as more competitors enter the market.
Can pharmacists substitute a biosimilar without a doctor’s permission?
It depends on the state and the drug. The FDA designates some biosimilars as “interchangeable,” meaning pharmacists can swap them for the original without consulting the prescriber. As of December 2025, 12 biosimilars have this status in the U.S., mostly for autoimmune drugs like Humira and Enbrel. For non-interchangeable biosimilars, the prescriber must specify “dispense as written.” This varies by state law and can delay adoption.
Why is the U.S. slower to adopt biosimilars than Europe?
Europe has simpler reimbursement systems and stronger government pressure to cut drug costs. In the EU, biosimilar adoption often exceeds 70% for many drugs. In the U.S., complex rebate systems, patent litigation, and provider reimbursement rules create barriers. For example, Medicare Part B pays providers based on the drug’s average sales price, so they earn more when patients use the expensive original. This creates a financial disincentive to switch. But that’s changing as payers like Cigna and UnitedHealthcare now offer $0 copays for biosimilars.
What’s the biggest biosimilar opportunity coming up?
Keytruda (pembrolizumab) is the biggest. It generated $25.5 billion in 2024 and treats multiple cancers. Fourteen companies are developing biosimilars, with the first expected in 2028. If even half the market switches, it could save the U.S. healthcare system over $5 billion annually. That’s more than the entire global biosimilars market in 2020.
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