By mid-2025, the pharmaceutical world will face its biggest shake-up in decades. A wave of patent expirations will hit, turning multi-billion-dollar drugs into cheap generics overnight. This isn’t just a legal footnote-it’s going to change how patients pay for medicine, how hospitals manage inventory, and how drug companies survive. The drugs at stake aren’t obscure treatments. These are the blockbuster patent expirations that defined modern medicine: drugs that made companies billions and kept millions alive. And now, their exclusive reign is ending.
What’s Expiring in 2025? Entresto Leads the Way
The first major blow comes in July 2025, when Novartis’ Entresto (sacubitril/valsartan) loses its core patent protection in the U.S. Entresto, a heart failure drug, brought in $7.8 billion in global sales in 2024. For patients, that meant paying $150 to $300 a month. Within months of generic entry, that cost will drop to $20-$40. Hospitals and pharmacy benefit managers are already preparing. Some systems have locked in 60% price cuts with insurers ahead of the expiry, just to avoid chaos.
Entresto’s patent expiration isn’t just about price. It’s about timing. The FDA approved the first generic version of sacubitril in October 2024-months before the patent even expires. That’s unusual. It signals that generic manufacturers are not just waiting-they’re racing. Twelve-seven abbreviated new drug applications (ANDAs) were filed targeting 2025 expirations alone, up 27% from the year before.
2026: Eliquis Goes Generic-And the Anticoagulant Market Collapses
November 2026 is when Bristol Myers Squibb and Pfizer’s Eliquis (apixaban) loses protection. In 2024, Eliquis made $13.2 billion globally. It’s the most prescribed blood thinner in the U.S., used to prevent strokes in atrial fibrillation patients. But unlike Entresto, Eliquis doesn’t have a monopoly on its market. Already, Xarelto, Pradaxa, and warfarin are out there. Once generics hit, prices will plummet faster than you think.
Small-molecule generics like Eliquis typically see 85-90% price drops within a year. Market share flips: 90%+ of prescriptions become generic within two years. Pharmacy technicians are already seeing manufacturers ramp up production. But there’s a catch-shortages. When Humira biosimilars launched, supply couldn’t keep up. That same scramble could happen again. One pharmacy group on Facebook reported staff worrying: “Will we run out in the first month?”
2028: The Giant Falls-Keytruda’s $30 Billion Patent Cliff
If Entresto and Eliquis are earthquakes, Keytruda’s 2028 expiration is a tsunami. Merck’s cancer immunotherapy generated $29.3 billion in sales in 2024. It’s the top-selling drug in the world. And it’s the only one of its kind for many patients with lung, melanoma, and head-and-neck cancers. No small-molecule drug can replace it. That’s why its patent expiry is so terrifying-for Merck, and for patients.
Keytruda is a biologic, not a small molecule. That means generics won’t be exact copies. They’ll be biosimilars-more complex, slower to develop, and harder to approve. The FDA has only approved a handful of biosimilars so far. But with $31.2 billion in potential revenue at risk for Merck, companies are already lining up. JPMorgan analysts predict Merck could lose $15 billion in annual revenue within 18 months of biosimilar entry. That’s more than most pharma companies make in a year.
Merck’s response? A $12 billion bet on next-gen cancer drugs. They’re betting their future on new therapies, not old ones. But for patients, the wait for biosimilars could mean years of high prices. Unlike Entresto, where generics arrive in months, Keytruda biosimilars may take 18-24 months to hit shelves after patent expiry.
Why This Wave Is Different
This isn’t the first patent cliff. Humira’s expiration in 2023 was big. But this one is bigger-by a lot. Between 2025 and 2030, $187 billion in global drug sales will lose protection. That’s 28% of the entire blockbuster drug market. The last time anything like this happened was in the early 2000s, when Lipitor went generic. But back then, the market was smaller. Today, drugs cost more, patients rely on them longer, and the financial stakes are higher.
What makes this wave unique is the concentration. Sixty-two percent of the $187 billion at risk comes from just three areas: oncology, cardiovascular, and immunology. Keytruda, Entresto, Eliquis, Ibrance, and Trulicity alone make up over half the value. These aren’t random drugs. They’re the backbone of modern treatment.
And the U.S. is where the money is. Even though Americans make up only 20% of the world’s population, they account for 63% of the revenue loss. Why? Because here, drug prices aren’t capped. In Europe or Canada, governments negotiate prices. In the U.S., companies set them-and they’ve set them high.
Who Wins? Who Loses?
Patients win. Families win. The U.S. healthcare system saves money. The Congressional Budget Office estimates $312 billion in savings over the next decade, with $198 billion of that coming between 2025 and 2027. For heart failure patients, that means switching from $300-a-month pills to $30 ones. For cancer patients, it could mean access to biosimilars they couldn’t afford before.
But the companies that made these drugs? They’re in trouble. Merck stands to lose 41% of its blockbuster revenue by 2030. Amgen could lose over half of its 2024 revenue. These aren’t small numbers. They’re existential. That’s why companies are buying smaller firms-Bristol Myers Squibb spent $4.1 billion on Karuna Therapeutics to build a new pipeline. Others are investing in gene therapy, AI-driven drug discovery, or new delivery systems.
Generic manufacturers are winning. Teva, Mylan, and Sandoz are leading the charge, with dozens of products in development. But even they face hurdles. Developing a generic costs $2.6 million and takes 3-4 years. And then there’s litigation. Biologics average 132 patents per drug-compared to 14 for small molecules. That means years of legal battles before a biosimilar can even reach the market.
What’s Next? The Rules Are Changing
Regulators are watching. The FTC is investigating more “pay-for-delay” deals, where brand-name companies pay generics to hold off on launching. In 2024, those investigations rose 23% year over year. The FDA is speeding up reviews. The Purple Book (for biologics) and Orange Book (for small molecules) now list over 1,200 drugs with upcoming expirations.
Hospitals are training staff. The American Society of Health-System Pharmacists found that 87% of hospital pharmacy directors are preparing for the 2025-2030 wave. They’re updating formularies, training nurses on substitutions, and even running early switch programs for patients on Entresto or Ibrance.
But there’s still a gap. Only 28% of U.S. states have laws allowing pharmacists to substitute complex generics like Entresto without a doctor’s approval. That’s not enough. Patients shouldn’t need a new prescription just because their drug went generic.
What This Means for You
If you’re a patient on one of these drugs-Entresto, Eliquis, Keytruda, Ibrance, or Trulicity-don’t panic. But do pay attention. Your doctor or pharmacist will likely reach out in the next year or two. You may be offered a cheaper version. Ask if it’s safe. Ask if it’s covered. Ask if you need to switch.
If you’re a caregiver, a pharmacist, or a hospital admin: start preparing now. Inventory systems need updating. Staff need training. Patients need education. The transition won’t be perfect. There will be delays. There might be shortages. But the savings? They’re real. And they’re coming faster than most people think.
The patent cliff isn’t a disaster. It’s a reset. For decades, drug prices rose because companies had exclusive control. Now, that control is ending. The question isn’t whether generics will arrive. It’s whether the system is ready for them.
OMG this is insane!! I’m on Eliquis and my copay’s already killing me-$40 a month?? Imagine if it drops to $5?? I’m gonna cry 😭
This is the most important public health shift in a generation, and barely anyone is talking about it outside of pharmacy circles. The $187 billion in potential savings isn’t theoretical-it’s real money that could fund insulin access, mental health services, and rural clinics. The fact that the U.S. pays 5x more than Canada for the same drugs is a moral failure, not an economic one.
Patients aren’t asking for free medicine-they’re asking for fair pricing. And now, with generics and biosimilars finally catching up, the market is being forced to correct itself. The pharma lobby will scream fraud, but the math doesn’t lie: 85% price drops on blockbuster drugs mean millions can actually afford to live.
Let’s not forget: Entresto was priced at $300/month because it could be. Not because it cost $300 to make. The innovation happened years ago. What we’re seeing now is the end of rent-seeking, not the end of innovation.
Agreed. The real story isn’t the patents expiring-it’s how long it took for the system to allow generics to compete. We’ve had 20 years of patent evergreening and pay-for-delay tactics. The fact that FDA approvals are accelerating now is a win for transparency.
Also, the biosimilar timeline for Keytruda is going to be a mess. Regulatory agencies need to standardize approval pathways or we’ll see another Humira-style bottleneck.
Wow, another one of those ‘pharma is evil’ hot takes. Let me guess-you think drug companies should just give away their R&D for free? The $12 billion Merck is investing in next-gen therapies? That’s not greed, that’s survival. Without patents, there’s no incentive to spend $2.6 billion developing one new cancer drug.
And don’t get me started on biosimilars. They’re not ‘generic’-they’re biologically complex. You can’t just copy a protein like you copy a pill. The FDA has to verify every batch. It takes years. So yes, prices won’t drop overnight. But they will drop. Eventually.
Bro, in India we’ve been buying generics for 20 years. Entresto? We got it for $12 a month. Eliquis? $8. Keytruda? Still waiting, but we’re not surprised. The U.S. is the last country on Earth that still believes in ‘drug magic pricing.’
Meanwhile, Merck’s CEO is on a yacht in Monaco, laughing. The real scandal isn’t the patent cliff-it’s that we let them charge this much in the first place. You think innovation costs $300 a pill? Nah. It costs $3. The rest is just profit padding.
Let’s be real-this isn’t about affordability. It’s about the collapse of the American healthcare illusion. You think your ‘insurance’ protects you? It doesn’t. It just hides the fact that you’re paying $15,000 a year for a pill that costs $3 to produce. The real villain isn’t Merck-it’s the system that lets them get away with it.
And don’t even get me started on the ‘innovation’ myth. Most ‘new’ drugs are just repackaged old ones with a new name. Keytruda? It’s basically just an immune checkpoint inhibitor. The science was published in 2002. We’re paying for nostalgia, not science.
Just talked to my hospital’s pharmacy director-she said they’ve already switched 40% of Entresto patients to generics in a pilot program. No adverse events. No issues. Patients are thrilled. The real problem? Doctors still don’t know how to explain it. Half of them think ‘generic’ means ‘inferior.’ It’s not. It’s the same molecule. Same bioavailability. Same FDA approval.
Stop being scared. Start being informed.