By mid-2025, the pharmaceutical world will face its biggest shift in decades. Dozens of top-selling drugs-each bringing in billions annually-will lose patent protection. This isn’t just a legal technicality. It’s a financial earthquake that will drop drug prices by 80% or more, change how doctors prescribe, and put billions back into patients’ pockets. The blockbuster patent expirations starting in 2025 aren’t scattered events. They’re a coordinated wave, and the drugs at the center of it are the ones millions rely on every day.
What’s Expanding in 2025? Entresto Leads the Way
The first major hit comes in July 2025, when Novartis’ Entresto (sacubitril/valsartan) loses its core patent protection in the U.S. This heart failure drug generated $7.8 billion in global sales in 2024. For patients, that means a monthly cost that’s been $150-$300 could drop to $20-$40 within months. Hospitals and pharmacies are already preparing. Over 87% of hospital pharmacy directors surveyed by ASHP in October 2024 are updating formularies and training staff for the switch. The FDA even approved the first generic version of sacubitril ahead of schedule in October 2024-unusually fast, signaling how heavily the industry is gearing up.
Why does this matter? Entresto isn’t a minor drug. It’s become the new standard of care for heart failure with reduced ejection fraction. When generics hit, doctors won’t just prescribe them-they’ll be encouraged to. Patient advocacy groups like the American Heart Association found that 68% of heart failure patients would switch immediately if cost dropped. That’s not just savings-it’s better access.
2026: Eliquis Falls-And the Anticoagulant Market Shifts
November 2026 is when Bristol Myers Squibb and Pfizer’s Eliquis (apixaban) loses its key crystalline form patent. In 2024, Eliquis raked in $13.2 billion globally. That’s more than the entire annual revenue of many mid-sized pharma companies. Once generics arrive, expect prices to plummet fast. Small-molecule drugs like Eliquis typically see 80-90% price drops within a year of generic entry, with generics capturing over 90% of the market within two years.
But here’s the twist: Eliquis isn’t alone. Other blood thinners like Xarelto and Pradaxa already have generics. So when Eliquis goes generic, it won’t just be competing with the brand-it’ll be in a crowded, price-war zone. Pharmacists are already watching supply chains closely. After Humira biosimilars caused initial shortages in 2023, many pharmacies are now building buffer stocks. One pharmacy technician on a major Facebook group noted: “We’re seeing multiple manufacturers ramping up, but I’m nervous about the first few months.”
2028: The Giant Falls-Keytruda’s $30 Billion Cliff
By far the biggest single event on this timeline is Merck’s Keytruda (pembrolizumab), which loses its core patent in 2028. In 2024, it brought in $29.3 billion-more than any other drug in history. It’s used to treat melanoma, lung cancer, Hodgkin’s lymphoma, and more. Unlike Entresto or Eliquis, Keytruda is a biologic. That means generics can’t just copy it. They have to make biosimilars, which are far harder to develop and get approved.
That’s why the impact won’t be immediate. Biosimilars take 18-24 months longer to reach market than regular generics. But when they do, the effect will be massive. JPMorgan analyst Christopher Schott predicts Merck could lose $15 billion in annual revenue within 18 months of biosimilar entry. That’s more than the entire market cap of many tech startups.
Merck isn’t sitting still. In November 2024, they announced a $12 billion investment in next-generation cancer therapies to replace Keytruda’s revenue. They’re betting on new immunotherapies, targeted drugs, and combination treatments. But even with innovation, the loss of Keytruda will reshape oncology. No other drug in history has had such a dominant position in cancer care. When biosimilars arrive, oncologists will have to decide: stick with the brand, or switch to a cheaper version that’s just as effective? The answer will depend on insurance coverage, hospital protocols, and patient trust.
Why This Wave Is Different: It’s Not Just One Drug-It’s 65 of Them
The 2025-2030 period isn’t just about Entresto, Eliquis, and Keytruda. According to IQVIA, 65 drugs with annual sales over $100 million will lose patent protection during this window. Together, they represent $187 billion in global sales at risk. That’s nearly 30% of the entire blockbuster drug market.
Here’s the breakdown by therapeutic area:
- Oncology (32%): Keytruda, Ibrance, Tecentriq, Opdivo
- Cardiovascular (25%): Entresto, Eliquis, Farxiga
- Immunology (20%): Humira (already started), Stelara, Rinvoq
- Diabetes (10%): Trulicity, Ozempic (patents later, but looming)
Each of these drugs has its own timeline, legal battles, and market dynamics. For example, Humira’s patent battles dragged on for years, delaying biosimilars until 2023. Now, those biosimilars are capturing over 40% of the market. That’s the blueprint for what’s coming next.
The Hidden Players: Generic Manufacturers Are Already in Position
Behind every patent expiration is a team of scientists, regulators, and business teams working for years to get ready. Generic drugmakers like Teva, Mylan, and Sandoz have been preparing since 2020. Teva alone has 37 products in development targeting these expirations. Mylan has 29. These companies spend an average of $2.6 million and 3-4 years to get each generic approved.
The FDA has received 127 applications for drugs expiring in 2025 alone-up 27% from last year. That’s not just a coincidence. It’s a race. The first generic to market often captures 80% of sales in the first month. After that, it’s a price war. That’s why companies are filing early, even before the patent expires, to get that first-mover advantage.
And it’s not just the U.S. The European Union, Canada, and Australia are also preparing. But the U.S. market is where the biggest money is. It accounts for 63% of the $187 billion in at-risk sales-even though it only has 20% of the world’s patients. Why? Because drug prices here are unregulated. A pill that costs $5 in Germany can cost $150 here. When patents expire, the drop is dramatic.
What This Means for Patients, Doctors, and Pharmacies
For patients, this is good news. The Congressional Budget Office estimates these expirations will save the U.S. healthcare system $312 billion over the next decade. $198 billion of that will happen between 2025 and 2027. For a heart failure patient on Entresto, that could mean $1,500-$3,000 saved per year. For a cancer patient on Keytruda, it could mean thousands less out of pocket.
But it’s not all smooth sailing. Doctors need to learn how to switch patients safely. Pharmacists need to manage inventory and substitution rules. In 63% of states, pharmacists can automatically substitute biosimilars-but only 28% have similar rules for complex generics like Entresto. That means confusion. A patient might get a different pill than expected. A doctor might not realize the switch happened.
That’s why organizations like ASHP and the American Medical Association are releasing toolkits. They’re training staff on therapeutic interchange, updating electronic records, and preparing patient education materials. One hospital system in California already negotiated 60% price reductions with pharmacy benefit managers before the generic even hit. They didn’t wait-they acted.
The Bigger Picture: Innovation, Consolidation, and the Future
Pharma companies aren’t just losing money-they’re being forced to change. Merck, BMS, and others are investing billions into new therapies: gene editing, RNA drugs, personalized cancer vaccines. Some analysts say innovation will replace 65-75% of lost revenue by 2030. Others think consolidation is inevitable. Goldman Sachs predicts 30% more mergers in pharma through 2026. By 2035, the top 10 drugmakers might shrink to 6 or 7.
Regulators are watching too. The FTC has seen a 23% jump in investigations into “pay-for-delay” deals-where brand companies pay generics to delay entry. Those deals are now illegal, but they still happen. The government is cracking down harder than ever.
One thing is clear: the era of sky-high prices for blockbuster drugs is ending. The tools to make cheaper versions exist. The demand is there. The patents are expiring. And for the first time in decades, patients-not just shareholders-are winning.
Which blockbuster drugs are losing patents in 2025?
The most significant drug losing patent protection in 2025 is Novartis’ Entresto (sacubitril/valsartan), a heart failure medication with $7.8 billion in 2024 sales. Its core combination patent expires in July 2025. Other drugs with 2025 expirations include certain formulations of diabetes and autoimmune drugs, but Entresto is the largest in terms of revenue impact.
What happens to drug prices after a patent expires?
After a patent expires, generic versions enter the market and prices typically drop 80-90% within 12 months for small-molecule drugs. For example, Entresto could fall from $300/month to under $40. Biosimilars for biologics like Keytruda see slower price drops-30-40% initially-because they’re harder to produce. Market share shifts quickly: generics capture over 90% of sales within two years for small molecules.
Why is Keytruda’s 2028 expiration such a big deal?
Keytruda is the highest-selling drug in history, bringing in $29.3 billion in 2024. It’s a biologic used in cancer treatment, meaning it can’t be copied directly. Biosimilars must be developed, which takes longer and costs more. When they arrive, Merck could lose up to $15 billion in annual revenue within 18 months. No other drug has had such a dominant position in oncology, making this the largest single patent cliff in pharmaceutical history.
How are pharmacies preparing for these expirations?
Hospitals and pharmacies are actively preparing. Over 87% of hospital pharmacy directors surveyed in late 2024 are updating formularies and training staff. Many are negotiating lower prices with pharmacy benefit managers ahead of time. Some are launching early-switch programs for patients. Supply chain teams are monitoring for potential shortages, especially after the Humira biosimilar rollout caused initial disruptions in 2023.
Will these patent expirations lower healthcare costs overall?
Yes. The Congressional Budget Office estimates the 2025-2030 patent expirations will save the U.S. healthcare system $312 billion over the decade, with $198 billion saved between 2025 and 2027. Patients will see immediate price drops-for example, Entresto generics could cut monthly costs by 85%. These savings will reduce insurance premiums and out-of-pocket spending, especially for chronic conditions like heart failure and cancer.
Kyle Flores
December 7, 2025 AT 03:00Man, I’ve been on Entresto for two years now. If this drops to $40 a month, I’m buying a damn motorcycle. No more choosing between meds and groceries.
Nancy Carlsen
December 8, 2025 AT 08:16This is literally life-changing for so many people 💗
Heart failure patients, cancer folks, diabetics-this isn’t just business, it’s human survival. Pharma’s been riding high for too long. Time for the people to win.
Jennifer Anderson
December 9, 2025 AT 11:17my mom’s on eliquis and she’s been crying about the cost for years. if this actually happens like they say… i don’t even know what to say. thank you to whoever made this post.
Oliver Damon
December 10, 2025 AT 06:21The structural shift here is non-trivial. We’re witnessing the commoditization of once-monopolistic therapeutic classes-small molecules first, then biologics. The margin compression will force R&D reallocation, likely accelerating targeted therapies and polypharmacology platforms. The 2025-2030 window isn’t just a patent cliff-it’s a systemic recalibration of value chains in biopharma.
What’s underappreciated is the regulatory arbitrage: the U.S. bears the brunt of pricing because of lack of price controls, while Europe and Canada absorbed biosimilar transitions more smoothly. This disparity will intensify pressure on CMS to reform reimbursement models.
Also, the 127 FDA filings for 2025 expirations alone indicate unprecedented pre-emptive preparation by generics. First-mover advantage isn’t just about market share-it’s about negotiating leverage with PBMs before the floodgates open.
The real test will be whether hospital systems can implement therapeutic substitution protocols without compromising outcomes. ASHP’s toolkits are a good start, but interoperability gaps in EHRs could cause dangerous inertia.
And let’s not ignore the geopolitical angle: China’s generic manufacturers are scaling up rapidly. If they enter the U.S. market aggressively post-2026, prices could drop even faster than projected.
Louis Llaine
December 10, 2025 AT 19:52Oh wow, so the ‘miracle drugs’ are finally going to be affordable? Shocking. Who would’ve thought the people who made billions off cancer patients might get called out for it?
Meanwhile, Merck’s CEO is probably sipping champagne in the Bahamas while his investors panic.
Kurt Russell
December 11, 2025 AT 13:18THIS IS HUGE. I’ve worked in oncology for 18 years. Keytruda was a godsend-but it was also a cash cow with a velvet rope. When biosimilars hit, we’ll finally be able to offer this to every patient who needs it, not just the ones with perfect insurance.
Pharma’s gonna scream ‘innovation crisis,’ but guess what? Real innovation isn’t about pricing-it’s about access. And now, finally, it’s coming.
Ashley Farmer
December 12, 2025 AT 17:35I just want to say thank you to the scientists and pharmacists who worked so hard to make these generics possible. It’s easy to forget the quiet heroes behind the scenes.
And to everyone who’s been paying $300/month for meds-you’re not alone. This is happening because people like us spoke up.
Sadie Nastor
December 13, 2025 AT 19:28my heart goes out to everyone who’s had to choose between medicine and rent. i hope this changes things for real. 🙏
Sangram Lavte
December 14, 2025 AT 23:56In India, we get generics for pennies. I remember my uncle taking a generic version of Eliquis for 80% less. Americans need to stop accepting this price gouging. It’s not about innovation-it’s about greed.
Jane Quitain
December 15, 2025 AT 07:46OMG I just texted my dad who’s on Humira-he’s gonna cry. This is the best news he’s heard in years. I’m so happy for everyone who’s been struggling.
Nicholas Heer
December 15, 2025 AT 22:58MARK MY WORDS: this is all part of the globalist agenda to destroy American pharma and hand control to China and the WHO.
They’re letting generics in so they can control the drug supply chain. Next thing you know, they’ll be forcing us to take ‘biosimilars’ made in state-run labs with no quality control.
Why is the FDA rushing approvals? Why are PBMs pushing this? It’s not about savings-it’s about control. Wake up.
David Brooks
December 16, 2025 AT 13:56Let me tell you something-when my sister got diagnosed with melanoma, Keytruda was her only shot. We sold our car to pay for it. Now? If a biosimilar comes in at $5,000 instead of $150,000? That’s not just a win. That’s a miracle.
Pharma execs can keep their bonuses. We just want our kids to live.