Blockbuster Patent Expirations 2025 and Beyond: What’s Expired, What’s Next, and How It Changes Your Medication Costs

What’s Really Happening with Drug Prices in 2025?

If you or someone you know takes a daily pill for heart failure, cancer, or blood clots, your out-of-pocket costs could drop by 80% or more starting next year. That’s not a guess-it’s the reality of the biggest wave of patent expirations in pharmaceutical history. Starting in July 2025, Entresto (sacubitril/valsartan) will lose its core patent protection in the U.S., opening the door for generic versions to hit pharmacy shelves. This isn’t an isolated event. Between 2025 and 2030, more than $187 billion in annual global sales from top drugs will become available to generic and biosimilar makers. For patients, that means cheaper meds. For pharmacies and insurers, it means major logistics shifts. For drugmakers, it’s a financial earthquake.

The 2025-2030 Patent Cliff: A Timeline of Key Drugs

Patent expirations don’t happen all at once. They roll out like a slow-motion avalanche, with some drugs losing protection months apart. Here’s what’s coming up, by year:

• July 2025: Entresto (Novartis) - The $7.8 billion heart failure drug loses its key combination patent (US8329752). Generic versions will be available immediately after this date.
• November 2026: Eliquis (Bristol Myers Squibb/Pfizer) - The $13.2 billion blood thinner’s main crystalline form patent expires. Multiple generic competitors are already approved and ready to launch.
• 2027: Ibrance (Pfizer) - The $4.8 billion breast cancer drug loses patent protection. Biosimilars are already in development, but small-molecule generics will enter faster.
• 2028: Keytruda (Merck) - The $29.3 billion cancer immunotherapy loses its core composition patent. This is the single largest patent expiration in history. No direct generic exists-it’s a biologic, so biosimilars will take longer to arrive.
• 2029-2030: Trulicity (Eli Lilly), Humira biosimilars (full market entry), and others follow. By 2030, nearly half of today’s top-selling drugs will be off-patent.

These aren’t obscure drugs. They’re the ones millions rely on every day. Entresto keeps heart failure patients alive longer. Eliquis prevents strokes. Keytruda helps people with advanced lung cancer live years longer than before. When these drugs go generic, the system changes.

Why Some Drugs Go Generic Faster Than Others

Not all drugs are created equal when it comes to patent expiration. There are two main types: small-molecule drugs and biologics.

Small-molecule drugs like Entresto and Eliquis are made from chemical compounds. Their formulas are easier to copy. Once the patent expires, generic manufacturers can produce identical versions in 6-12 months. These generics typically drop to 10-20% of the brand price within a year. In the case of Entresto, patients paying $300 a month could soon pay $30.

Biologics like Keytruda are made from living cells. They’re far more complex. You can’t just copy the recipe-you have to recreate the entire biological process. That’s why biosimilars take 18-24 months to get approved after patent expiry. Even then, they’re not exact copies. They’re “similar enough.” As a result, they only cut prices by 30-40% initially, and it takes 3-5 years for them to capture half the market.

The FDA’s Orange Book lists all small-molecule patents. The Purple Book tracks biologics. Both are public, and pharmacy teams use them daily to plan for upcoming expirations.

Who Wins and Who Loses When Patents Expire

When a blockbuster drug loses patent protection, the winners are clear:

• Patients - Lower copays. Many will switch to generics immediately. A 2024 American Heart Association survey found 68% of heart failure patients would switch to generic Entresto the moment it’s available.
• Insurers and PBMs - Lower drug spend means lower premiums. The Congressional Budget Office estimates these expirations will save the U.S. healthcare system $312 billion between 2025 and 2035.
• Generic manufacturers - Companies like Teva, Mylan, and Sandoz are investing billions to be first to market. Teva alone has 37 products in development targeting the 2025-2030 cliff.

The losers? The drugmakers who built their businesses on these drugs.

• Merck could lose up to $31 billion in revenue by 2030, mostly from Keytruda.
• Bristol Myers Squibb stands to lose $13 billion from Eliquis alone.
• Novartis will see a major hit from Entresto’s $7.8 billion in annual sales.

These companies aren’t sitting still. Merck is pouring $12 billion into next-gen cancer drugs. BMS bought Karuna Therapeutics for $4.1 billion to build a new pipeline. They’re betting on innovation to replace the lost revenue.

What Happens in Pharmacies When Generics Arrive

It’s not just about new pills on the shelf. Pharmacies and hospitals are preparing for a massive operational shift.

By October 2024, 87% of hospital pharmacy directors said they were already adjusting inventory, training staff, and negotiating new prices with pharmacy benefit managers (PBMs). Some hospitals have already locked in 60% price cuts for Entresto in anticipation of the July 2025 launch.

Pharmacists are learning how to explain the switch to patients. Many are worried about confusion. “I’ve seen patients panic when their brand drug disappears,” said one pharmacist on Reddit. “They think the generic is weaker. It’s not. It’s the same thing, just cheaper.”

There’s also a risk of shortages. When Humira’s biosimilars launched in 2023, there were supply chain hiccups. Pharmacists are now on alert. “We’re not waiting until the last minute,” said Sarah Johnson, a pharmacy tech with 142,000 followers on Facebook. “We’re stocking up early.”

Why This Matters More in the U.S. Than Anywhere Else

Patent expirations happen worldwide. But the U.S. feels this more than any other country.

Why? Because the U.S. doesn’t regulate drug prices. In Europe or Canada, governments cap what a drug can cost-even before patents expire. In the U.S., prices are set by the market. That means when a drug like Keytruda costs $150,000 a year, that’s what insurers and patients pay.

When generics arrive, the price drop is dramatic. In Europe, Entresto might cost $1,200 a year. In the U.S., it’s $3,600. After generics hit, that could fall to $400. That’s why the U.S. accounts for 63% of the $187 billion in at-risk revenue-even though it has only 20% of the world’s patients.

That’s also why the FDA has received 127 new generic applications for 2025 expirations-a 27% jump from last year. Companies know the U.S. market is worth fighting for.

What You Should Do Now

If you’re on one of these drugs, here’s what to do:

1. Know your drug - Is it a small molecule (like Eliquis) or a biologic (like Keytruda)? Check the FDA’s Orange Book or Purple Book.
2. Ask your doctor or pharmacist - When is the patent expiring? When will generics be available? Don’t wait until your prescription runs out.
3. Check your insurance plan - Many PBMs will automatically switch you to the generic. But some require prior authorization. Call now.
4. Consider switching early - If your insurer offers a discount now, take it. There’s no downside. Generics are just as safe and effective.

Don’t assume your doctor will bring it up. Most are focused on treatment, not cost logistics. You have to be your own advocate.

What Comes After the Patent Cliff?

By 2030, the pharmaceutical industry will look completely different. The top 10 drugmakers could shrink to six or seven after mergers. Innovation will shift toward gene therapies, RNA drugs, and AI-designed molecules. But for now, the focus is on surviving the next five years.

The patent cliff isn’t just a financial event. It’s a human one. It means a diabetic patient in Ohio can afford their insulin. A cancer patient in Texas can keep taking Keytruda without bankruptcy. A grandmother in Florida can fill her heart medication without choosing between groceries and pills.

This isn’t the end of big pharma. It’s the beginning of a fairer system-one where life-saving drugs aren’t locked behind corporate patents for decades. The timeline is set. The science is ready. The only question left is: Are you prepared to use it?