Lp(a) drugs from Novartis, Amgen and Eli Lilly aim to prevent heart attacks

Pharma thinks it’s found the next frontier in preventing heart attacks. 

Novartis, Amgen and Eli Lilly are among the drugmakers betting that slashing levels of a particularly bad form of cholesterol could deliver the next blockbusters in cardiology. All three of the pharmaceutical giants are in late-stage trials to test whether drugs that cut Lp(a) can protect people from heart attacks.

If they can, the opportunity could be massive: an estimated one in five people worldwide have elevated Lp(a), and there’s not much they can do to lower it. Evidence from human genetics suggests the idea could work, but drugmakers don’t know for sure. That makes the first late-stage trial results from Novartis, expected later this year, important for the entire pipeline. 

“History has taught us you can’t make assumptions,” said Dr. Steve Nissen, chief academic officer of the Heart, Vascular & Thoracic Institute at Cleveland Clinic who is the principal investigator of Novartis’ Phase 3 Horizon trial of pelacarsen, the company’s experimental drug to lower Lp(a). “We thought raising HDL would be beneficial and that didn’t work, so I think we have to keep an open mind.”

Lp(a), or lipoprotein(a), was first discovered in 1963. It’s a more dangerous cousin to the well-known LDL cholesterol because it simultaneously clogs arteries and promotes blood clots, posing two risks with just one particle. Almost 50 years after Lp(a) was discovered, researchers found that people who have high levels of it had a more than twofold higher risk of heart attack than those who don’t. 

How much Lp(a) a person has circulating in their body is almost entirely determined by their genes. Lifestyle factors like diet and exercise don’t influence Lp(a) levels like they do LDL levels, leaving people with few good options to reduce it. 

Currently, doctors encourage people to focus on the factors they can change, such as lowering their LDL cholesterol, decreasing blood pressure, treating obesity and diabetes and exercising. Those strategies can help protect people from high Lp(a) for some time, Nissen said. New medicines could treat people for a longer time. 

Novartis, Amgen and Lilly have already proven their experimental drugs slash levels of Lp(a) by more than 80%. Now, they will need to show that translates into tangible benefits. If that happens, the drugs could reach annual sales of $5.6 billion by 2032, according to consensus estimates from Evaluate, a pharmaceutical commercial intelligence firm.

“We don’t know how much you have to lower levels,” Nissen said. “We don’t know how high you have to be to benefit from getting your level lowered. Estimates of how much you have to lower levels to prevent events based upon genetic studies are highly variable, so we don’t have an answer, and we won’t have an answer until on the date that we unblind the trial.”

That should happen around the middle of the year, Novartis CEO Vas Narasimhan said on the company’s fourth-quarter earnings call in February….