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

By mid-2025, millions of Americans will start seeing their monthly prescription bills drop by 80% or more. Not because of insurance changes, not because of coupons - but because the patents protecting some of the most expensive drugs in history are finally running out. This isn’t a slow shift. It’s a financial earthquake in the pharmacy aisle, and it’s already starting.

What Exactly Is a Patent Expiration?

A pharmaceutical patent gives a company exclusive rights to sell a drug without competition. For about 20 years from the original filing date - often stretched even longer with extra patents on formulations, delivery methods, or uses - no one else can make the same medicine. When that protection ends, generic manufacturers can step in and sell chemically identical versions at a fraction of the price.

It sounds simple, but the system is full of layers. A drug like Entresto doesn’t just have one patent. It has dozens: one for the chemical combo, another for how it’s made, another for how it’s taken, another for treating a specific type of heart failure. These are called patent thickets. Companies use them to delay generics, sometimes for years after the core patent expires.

But starting in 2025, those layers are starting to fall. The FDA has approved dozens of generic versions ahead of schedule. Hospitals are already changing their formularies. Pharmacies are stocking up. Patients are asking their doctors: "Will my pill look different next month?" And the answer is yes - and cheaper.

The 2025-2030 Patent Expiration Timeline: Key Drugs and Dates

The next five years are packed with drug expirations worth more than $187 billion in global sales. Here’s what’s coming:

• Entresto (sacubitril/valsartan) - Novartis | U.S. core patent expires July 2025 | 2024 sales: $7.8 billion
• Eliquis (apixaban) - Bristol Myers Squibb & Pfizer | Key crystalline patent expires November 2026 | 2024 sales: $13.2 billion
• Trulicity (dulaglutide) - Eli Lilly | Core patent expires 2027 | 2024 sales: $9.1 billion
• Ibrance (palbociclib) - Pfizer | Patent expires 2026 | 2024 sales: $5.4 billion
• Keytruda (pembrolizumab) - Merck | Core composition patent expires 2028 | 2024 sales: $29.3 billion

These aren’t obscure drugs. They’re the backbone of modern treatment for heart failure, cancer, diabetes, and blood clots. Entresto alone is prescribed to over 1.2 million Americans with heart failure. Eliquis is the most-prescribed blood thinner in the U.S., replacing warfarin for millions.

What makes 2025 stand out? It’s the first year where multiple billion-dollar drugs lose protection at once. Entresto’s July 2025 expiration isn’t just a date - it’s a trigger. Generic manufacturers have already filed applications. The FDA has approved the first version of sacubitril ahead of schedule. Retail pharmacies are preparing for supply chain shifts. And patients? They’re already seeing price drops in clinical trials and hospital systems.

Why Entresto’s 2025 Expiration Is a Game-Changer

Entresto isn’t just another drug. It’s a breakthrough. Before Entresto, heart failure patients took ACE inhibitors or beta blockers - drugs from the 1980s. Entresto, approved in 2015, cut hospitalizations and deaths by 20% in clinical trials. But it cost $150-$300 a month without insurance.

By mid-2025, generic versions will cost $20-$40. That’s not a discount. That’s a revolution.

Doctors like Dr. Emily Chen in California are already preparing their patients. "I’m telling them now: by August, your pill will look different. It’ll be just as effective, but you’ll pay less than a coffee a day," she said in a September 2024 post on the Sermo physician network.

But it’s not just about price. It’s about access. In a 2024 American Heart Association survey, 68% of heart failure patients said they’d switch to the generic immediately - not because they distrust it, but because they can’t afford the brand anymore. For many, Entresto was the difference between treatment and skipping doses.

And it’s not just patients. Hospitals are already negotiating 60% price reductions with pharmacy benefit managers (PBMs) in anticipation of the generic launch. One hospital system in Ohio reported saving $2.1 million in the first quarter of 2025 just by switching 300 patients to the generic ahead of schedule.

Keytruda: The Billion Elephant in the Room

If Entresto’s expiration is a tidal wave, Keytruda’s is a tsunami.

Merck’s cancer immunotherapy brought in $29.3 billion in 2024 - more than any other drug in history. It’s used for melanoma, lung cancer, Hodgkin’s lymphoma, and more. And it has no direct competitors. Unlike blood thinners or heart meds, there’s no chemical alternative to Keytruda. Only biosimilars - and those take longer to develop.

Its core patent expires in 2028, but the race is already on. At least 12 biosimilar companies are in late-stage trials. The FDA has fast-tracked several applications. But because biologics are made from living cells - not just chemicals - they’re harder to copy. That means the first biosimilars won’t hit shelves until late 2028 or early 2029.

And even then, they won’t be cheap right away. Biosimilars typically cut prices by only 30-40% at first, compared to 80% for generics. Why? Because doctors are cautious. Patients are scared. Insurance companies are still figuring out how to cover them.

But Merck knows the clock is ticking. In November 2024, the company announced a $12 billion investment in next-generation cancer drugs - new immunotherapies, gene therapies, and targeted treatments - to replace the revenue lost when Keytruda’s patent expires.

What This Means for You: Lower Costs, But Watch for Pitfalls

For patients, this is good news. You’ll pay less. But it’s not all smooth sailing.

• Switching meds isn’t automatic. Your doctor or pharmacist won’t switch you without telling you. Some states don’t allow pharmacists to substitute certain generics without a doctor’s approval - especially for complex drugs like Entresto.
• Supply shortages could happen. When Humira’s patents expired, there were delays. Manufacturers couldn’t ramp up fast enough. The same could happen with Entresto or Eliquis in 2025-2026.
• Insurance plans might change. PBMs will push generics hard. Your plan might stop covering the brand-name version entirely. You might get a letter saying your drug is no longer on formulary. Don’t panic - it just means you’ll get the generic.
• Don’t assume "generic" means "inferior." The FDA requires generics to be bioequivalent - meaning they work the same way, in the same amount of time, with the same safety profile.

Here’s what to do now:

1. If you’re on Entresto, Eliquis, Trulicity, or Ibrance - ask your doctor in early 2025 if a generic will be available soon.
2. Call your pharmacy and ask if they’re stocking the generic versions. Many will start carrying them weeks before the official expiration date.
3. Check your insurance formulary. You might need to switch to the generic to avoid higher copays.
4. Don’t stop taking your medication. Even if the brand runs out, the generic will be there.

Who Benefits? Who Loses?

The biggest winners? Patients. The U.S. healthcare system. The federal government.

The Congressional Budget Office estimates these expirations will save the U.S. $312 billion between 2025 and 2035. About $198 billion of that will come in just the first three years - 2025 to 2027.

Generic manufacturers like Teva, Mylan, and Sandoz are investing billions to be ready. Teva alone is developing 37 drugs targeting this patent cliff. They’re the ones who’ll make the profits - and keep prices low.

The losers? The big pharma companies. Merck could lose up to $31 billion in revenue by 2030. Bristol Myers Squibb faces a 50% drop in Eliquis revenue after 2026. That’s why they’re buying smaller biotech firms - like BMS’s $4.1 billion purchase of Karuna Therapeutics - to replace lost income.

And while patients save money, some small clinics and pharmacies might struggle. If a hospital’s entire budget was built around high-margin brand-name drugs, switching to generics can hurt cash flow. That’s why 87% of hospital pharmacy directors are already training staff on the transition.

What’s Next After 2030?

The patent cliff doesn’t end in 2030. It just changes shape.

After 2030, more biologics will expire - drugs like Humira’s biosimilars, which are still gaining traction. New cancer drugs, autoimmune treatments, and rare disease therapies will enter the market. But they’ll come with their own patents, their own delays, their own battles.

What’s different now? The system is waking up. Regulators are approving generics faster. Pharmacies are preparing better. Patients are more informed. And the financial pressure is forcing innovation.

The next decade won’t be about protecting old drugs. It’ll be about creating new ones that can’t be copied easily - gene therapies, mRNA treatments, personalized cancer vaccines. And that’s where the real future of medicine lies.

For now, if you’re on one of these blockbuster drugs, take a breath. The cost is about to drop. You don’t need to wait for a letter. Don’t wait for your doctor to bring it up. Ask. Now. Because the change is already here - and it’s cheaper than you think.