Heart Disease, a Historic Strength for Big Pharma, Becomes a Weakness - Heard on the Street -- WSJ

By David Wainer

There is a strange paradox haunting healthcare investing right now.

Heart disease remains humanity's top killer, yet for drugmakers and Wall Street, it is becoming one of the hardest places to make money.

The past few months drove this home, with billions in market value vanishing. Novo Nordisk stock fell in late July when it revealed that its bet on dampening inflammation failed to prevent heart attacks and strokes. Just over a month later, Novartis's much-watched cholesterol study fell flat too.

The industry has poured billions into enormous, yearslong studies meant to prove it can save lives by hitting certain biological targets. The irony is that the recently failed drugs did exactly what they were designed to do. Novartis said that its drug pelacarsen successfully lowered a fatty particle in the blood known as Lp(a). Yet the goal that actually matters, fewer heart attacks and strokes, keeps slipping away.

This is partly a legacy of the industry's past success: Already available treatments have significantly driven down cardiovascular risk. Proving a new medicine's worth today is a bit like trying to show air bags save lives when everyone is already buckled up: once you have one layer of protection, proving a second one adds meaningful benefit is genuinely hard.

That means enrolling ever more patients and waiting longer to catch enough cardiovascular "events" to show statistical benefit. Companies end up having to spend hundreds of millions of dollars in massive studies that track thousands of patients for years. "This isn't a vaccine study, where you jab people and see them in a year," says William Blair analyst Myles Minter. "These patients are under constant monitoring-visits, blood draws, EKGs-for years. That's why the costs are astronomical."

Then there is the commercial gauntlet. Even a drug that works enters a market of dirt-cheap generics. Amgen's Repatha, an injection that drives LDL cholesterol far lower than statins alone and cuts the risk of heart attacks and strokes, struggled commercially for years, forcing Amgen to cut its U.S. list price sharply after insurers restricted access.

It wasn't always this way. For decades, doctors barely understood why people suffered sudden heart attacks and strokes. Beginning in the mid-20th century, studies pinned the blame on risk factors like high blood pressure and cholesterol. The drugs that followed, including statins and blood-pressure pills, became some of the biggest blockbusters in medicine.

Those drugs have since gone generic and are widely accessible, but people keep dying of heart disease at stubbornly high rates, suggesting other culprits are at work. Lp(a) became one of the industry's biggest bets. The cholesterol-carrying particle is similar to LDL, but it may be more damaging and its levels are largely determined by genetics. The logic was simple: lower Lp(a) and you should lower the risk of heart attack and stroke. Novartis, Eli Lilly, Amgen and AstraZeneca poured billions into these programs.

Then Novartis announced earlier this month that pelacarsen had failed to reduce cardiovascular events. Researchers will debate the full data at the American Heart Association meeting in November, including whether the dose was high enough and whether the trial enrolled the right patients. Rival drugs that lower Lp(a) even further have yet to report, and they may still succeed. But investors didn't wait to reprice the risk. Amgen shares had their worst day in decades as the market questioned whether the Lp(a) hypothesis itself is flawed.

The puzzling part is how strong the genetic case looks. Researchers have found that those born with genetic variants that produce higher Lp(a) levels consistently face greater risks of heart attack and stroke. Proving that a drug can reverse that risk, though, is another matter. One likely explanation: Genetic risk builds over a lifetime, and the Novartis trial had only a few years to undo it.

A similar blow came at Novo Nordisk. Its drug ziltivekimab was designed to block IL-6 and reduce inflammation linked to heart disease. It hit its biological target, lowering markers of inflammation, but failed to reduce major cardiovascular events. The failure highlighted the same problem as the Novartis miss: changing a biological marker isn't the same thing as preventing a heart attack or stroke.

That doesn't mean cardiovascular drug development is grinding to a halt. There are bright spots. Obesity drugs like Wegovy have emerged as cardiovascular successes, while treatments for rare genetic heart conditions continue to show promise. But on a grand scale, expect a period of retrenchment as companies reassess which targets are worth pursuing and which patients are most likely to benefit.

Cardiovascular drug development is starting to look a bit like the modern oil industry. The easy wells have been tapped. What's left is in deep water: expensive, technically perilous and less likely to strike oil.

The reserves are still there. They are just getting much harder and more expensive to reach.

Write to David Wainer at david.wainer@wsj.com

(END) Dow Jones Newswires

September 12, 2026 05:30 ET (09:30 GMT)