by Caspian Whitlock - 0 Comments

By mid-2025, the pharmaceutical industry will hit a turning point unlike anything seen in the last 30 years. Dozens of top-selling drugs, each bringing in billions annually, will lose patent protection. This isn’t a slow fade-it’s a cliff. And it’s already starting. The drugs at the center of this shift aren’t obscure generics or niche treatments. These are the blockbuster patent expirations that changed how doctors treat cancer, heart failure, and blood clots. Their loss of exclusivity will slash prices, shift prescriptions, and reshape how healthcare systems operate worldwide.

What’s Expiring in 2025? Entresto Leads the Way

The first major hit comes in July 2025: Novartis’ Entresto (sacubitril/valsartan). This heart failure drug generated $7.8 billion in global sales in 2024. It’s not just popular-it’s life-changing for patients with reduced ejection fraction. But its core patent (US8329752) expires that month, and the FDA has already approved the first generic version of sacubitril ahead of schedule. That’s rare. It signals how prepared the generic industry is.

What does this mean for patients? Right now, many pay $150 to $300 a month out of pocket. Within months of generic launch, that could drop to $20-$40. Hospitals are already planning formulary switches. Pharmacies are stocking up. Patients are being warned. This isn’t theoretical-it’s happening.

2026: Eliquis Hits the Wall

Just over a year later, in November 2026, Bristol Myers Squibb and Pfizer’s Eliquis (apixaban) loses its key crystalline form patent (US8278323). Eliquis brought in $13.2 billion in 2024 alone. It’s one of the most prescribed blood thinners in the U.S., beating out older drugs like warfarin because it doesn’t require constant monitoring.

But here’s the catch: the anticoagulant market is already crowded. Xarelto, Pradaxa, and now generics of older drugs are waiting in the wings. Once Eliquis goes generic, price drops will be brutal-likely 85%+ within a year. Market share will flip fast. Within two years, generics will control over 90% of prescriptions. That’s the pattern for small-molecule drugs like this. No drama, just math.

2028: The Big One-Keytruda

If Entresto and Eliquis are earthquakes, Keytruda is a tsunami. Merck’s pembrolizumab, sold as Keytruda, raked in $29.3 billion in 2024. It’s the first-line treatment for melanoma, lung cancer, and several other cancers. And it’s the only drug in its class with such massive scale.

Its core composition-of-matter patent expires in 2028. No other drug works exactly like it. That means biosimilars-not generics-will enter the market. Biosimilars are harder to make. They’re biologics, complex proteins grown in living cells. Developing them takes years, costs hundreds of millions, and requires extensive clinical trials.

So while generic Entresto will be on shelves by August 2025, the first Keytruda biosimilar won’t arrive until late 2029 or early 2030. But when it does, Merck could lose $15 billion in annual revenue within 18 months. That’s the biggest single-year revenue drop in pharmaceutical history, according to JPMorgan analysts. Merck is already betting big-$12 billion in new R&D focused on next-gen oncology drugs to fill the gap.

Giant translucent pills float down a hospital corridor, dissolving into light as patients walk peacefully.

Why This Timeline Matters: The Bigger Picture

This isn’t just about three drugs. Between 2025 and 2030, 65 blockbuster medications with combined sales of $187 billion will lose exclusivity. That’s nearly a third of the entire global blockbuster market. The biggest chunks? Oncology (32%), cardiovascular (25%), and immunology (20%).

Here’s the breakdown by drug type:

  • Small-molecule drugs (like Eliquis, Entresto): Generic versions are chemically identical. Faster to make. Price drops 80-90% within a year. Market share hits 90%+ in two years.
  • Biologics (like Keytruda): Biosimilars are similar but not identical. Harder to replicate. Slower approval. Price drops only 30-40% initially. Market share takes 3-5 years to reach 75%.

And the U.S. bears the brunt. Even though it has only 20% of the world’s patients, it accounts for 63% of the $187 billion at risk. Why? No government price controls. Drugmakers charge what the market will bear. When patents expire, U.S. patients see the biggest savings.

Who’s Ready? Who’s Not?

Generic manufacturers are moving fast. Teva has 37 products in development targeting upcoming expirations. Mylan and Sandoz aren’t far behind. The FDA has received 127 new generic applications just for 2025 expirations-a 27% jump from last year.

But it’s not just about making the drug. It’s about getting it into hospitals and pharmacies. Hospital systems are ahead of the curve. ASHP’s 2024 survey found 87% of hospital pharmacy directors are already changing inventory systems and training staff. Retail pharmacies? Slower. On average, they wait 5.7 months after generic approval to switch. Hospitals do it in 3.2.

Patients? Most are ready. A survey by the American Heart Association found 68% of heart failure patients would switch to generic Entresto the moment it’s available. Cost is the main driver. For many, the brand was unaffordable.

A glowing biologic tree sheds leaves that become winged biosimilars, chased by shadowy figures in a stormy garden.

The Hidden Costs: Litigation, Patents, and Delays

Don’t assume everything goes smoothly. Drugmakers don’t give up easily. They build patent thickets-dozens of secondary patents on delivery systems, dosing schedules, or manufacturing methods. For biologics like Keytruda, companies file an average of 132 patents per drug. Small molecules? Around 14.

These secondary patents are used to delay generics. Some lawsuits can push market entry back by two years. The FTC is cracking down on "pay-for-delay" deals-where brand companies pay generics to stay off the market. Investigations into these agreements rose 23% last year.

And even when generics arrive, switching isn’t automatic. Only 28% of U.S. states have laws allowing pharmacists to substitute complex generics like Entresto without a doctor’s OK. For biosimilars, 63% of states allow substitution-but only if the FDA designates them as "interchangeable." That status is still rare.

What Comes Next? The Aftermath

By 2030, the industry will have lost 41% of its current blockbuster revenue. Merck could lose $31.2 billion. Amgen could lose over half its 2024 revenue. That’s why mergers are picking up. Bristol Myers Squibb just bought Karuna Therapeutics for $4.1 billion to strengthen its neuroscience pipeline ahead of Eliquis’ fall. Other companies are shifting focus to gene therapies, AI-driven drug discovery, and targeted oncology drugs.

Meanwhile, the U.S. healthcare system will save $312 billion over the next decade, with $198 billion saved between 2025 and 2027 alone. Patients will pay less. Insurers will pay less. Medicaid and Medicare will see lower costs.

But the real winners? Patients who couldn’t afford these drugs before. A man in Ohio with heart failure switching from $250/month Entresto to $30/month generic. A woman in Texas with stage IV lung cancer finally getting Keytruda without bankruptcy. That’s the quiet revolution happening behind the numbers.

How to Track What’s Next

If you’re a patient, caregiver, or healthcare worker, you don’t need to guess. Use the FDA’s Orange Book (for small molecules) and Purple Book (for biologics). Both list every patent and expiration date. The Generic Pharmaceutical Association also offers a free "Patent Cliff Navigator" tool-used by 82% of pharmacy benefit managers. It shows month-by-month expirations, who’s developing generics, and when they’re expected to launch.

Stay informed. The next big shift isn’t far off.

What does "patent expiration" mean for my medication?

When a drug’s patent expires, other companies can legally make and sell identical or similar versions at a fraction of the cost. For small-molecule drugs like Entresto or Eliquis, these are called generics. For biologics like Keytruda, they’re called biosimilars. You’ll still get the same treatment, but your out-of-pocket cost could drop by 80% or more.

Will my doctor switch me to a generic automatically?

Not always. In most states, pharmacists can substitute a generic for a brand-name drug unless your doctor writes "dispense as written." But for complex drugs like Entresto, substitution rules vary. Some states require a new prescription. Always check with your pharmacist or provider before switching.

Are generic drugs as safe and effective as brand-name ones?

Yes. The FDA requires generics to have the same active ingredient, strength, dosage form, and route of administration as the brand. They must also meet the same strict quality standards. For biosimilars, the FDA requires extensive testing to prove they work the same way with no clinically meaningful differences.

Why does it take so long for biosimilars to arrive after a patent expires?

Biosimilars are made from living cells, not chemicals. That makes them far more complex to replicate than small-molecule drugs. Developing one can take 7-10 years and cost over $100 million. Plus, manufacturers must run large clinical trials to prove safety and effectiveness. That’s why it takes 18-24 months after patent expiry for biosimilars to launch, compared to 6-12 months for generics.

How will this affect drug prices in the long term?

Prices will drop sharply after generics or biosimilars enter the market. For small molecules, expect 85-90% price reductions within a year. For biologics, reductions are slower-around 30-40% in the first year, rising to 60-70% over five years. These savings will flow to insurers, Medicare, Medicaid, and ultimately, patients at the pharmacy counter.