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Experimental Pill May Be New Way to Control Cholesterol
  • Posted November 7, 2022

Experimental Pill May Be New Way to Control Cholesterol

Millions of people take daily medication to lower their cholesterol levels and prevent heart attacks, but there hasn't been a drug that targets a dangerous type of cholesterol in the blood known as lipoprotein(a), or Lp(a).

That's why a new study of an investigational drug called olpasiran, which blocks the production of apolipoprotein(a) — a key component of Lp(a) — is generating a lot of excitement in scientific circles.

“Unlike other types of cholesterol, there is, unfortunately, no approved treatment that is currently available to lower Lp(a),” explained study author Dr. Michelle O'Donoghue, a cardiovascular medicine specialist at Brigham and Women's Hospital in Boston.

Olpasiran binds to the body's own mRNA, to prevent it from making apolipoprotein(a).

The study looked at different doses of the new drug in about 230 people with high levels of Lp(a). Folks who received the highest doses of olpasiran in the study reduced their Lp(a) concentration by more than 95% compared with placebo. The drug is given via injection every 12 weeks.

Study patients' Lp(a) levels were about 260.3 nanomoles per liter of blood (nmol/L), on average, when the study started. The U.S. Centers for Disease Control and Prevention defines high Lp(a) levels as greater than 125 nmol/L. Most people in the study were also taking drugs to lower their cholesterol levels, mainly statins.

What's more, the treatment was safe. Injection site reactions were more common with olpasiran than a placebo shot, but they tended to be mild and resolve on their own, O'Donoghue said.

A phase 3 trial will be launching in December to evaluate the efficacy and safety of olpasiran, she added.

Millions of people take statins or other drugs to lower their cholesterol levels, but these drugs mainly target low-density lipoprotein (LDL) cholesterol, she explained.

“Statins don't lower Lp(a) [and] statins may even raise Lp(a)," O'Donoghue said. “That's one of the reasons that it's exciting to have a novel therapy in development that leads to such a marked and sustained reduction in Lp(a).”

The findings were presented Sunday at the American Heart Association (AHA) annual meeting, in Chicago, and were published simultaneously Nov. 6 in the New England Journal of Medicine.

Lp(a) is potentially the most dangerous molecule in the blood, and high levels increase the risk of heart attack, stroke and death, said Dr. Manesh Patel, chief of the division of cardiology and the division of clinical pharmacology at Duke University School of Medicine in Durham, N.C. He is also the chair of the AHA's 2022 council on scientific sessions programming.

“Historically, we have not tested people for it because we didn't have therapies,” said Patel, who was not involved in the study. Lp(a) does tend to travel with high levels of LDL cholesterol, he added.

“The new drug is a very effective therapy to reduce Lp(a), and now we will await phase 3 trial results to see if this translates into improvements in cardiovascular outcomes such as lower rates of heart attack, stroke and death,” Patel said.

His advice? Ask your doctor about testing for Lp(a) if you have a family history of heart disease, Patel said.

“If it is elevated, consider doing everything else you can to lower your risk for heart disease and stroke,” he advised. “This information can motivate people to make changes such as eating a healthier diet, exercising and controlling other risk factors such as high blood pressure. Lp(a) may move a little bit, too.”

More information

The U.S. National Institutes of Health has more on Lp(a).

SOURCES: Michelle O'Donoghue, MD, MPH, cardiovascular medicine specialist, Brigham and Women's Hospital, Boston; Manesh Patel, MD, chief, division, cardiology and clinical pharmacology, Duke University School of Medicine, Durham, N.C., and chair, AHA 2022 council on scientific sessions programming; American Heart Association annual meeting, Nov. 5 to 7, 2022; New England Journal of Medicine, Nov. 6, 2022

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