A new drug cuts nearly 86% of the genetic form of cholesterol

CHICAGO: The highest dose of an experimental pill developed by Eli Lilly significantly reduced an inherited form of high cholesterol in a mid-stage trial, according to data presented at a medical meeting Monday .

The researchers reported at the American Heart Association meeting in Chicago.

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Lilly’s drug is the only oral treatment among several injectable therapies being tested to treat high Lp(a), a risk factor for heart disease that affects one in five people worldwide. bridge.

Unlike low-density lipoprotein, or LDL, so-called bad cholesterol that can be treated with diet and statins, there are no approved treatments for Lp(a) and few people know that they have this disease.

Elevated Lp(a) can significantly increase the risk of heart attack, stroke, aortic valve stenosis and peripheral artery disease, a buildup of fatty plaques in the arteries. People of African and South Asian descent are most at risk.

The trial compared three daily doses of muvalaplin – 10, 60 and 240 milligrams – with placebo in 233 adults with high Lp(a) levels. The researchers tested Lp(a) levels using a traditional blood test and a new method that measures the level of intact Lp(a) particles in the blood.

Muvalaplin reduced Lp(a) by 47.6% at the 10 mg dose, 81.7% at the 60 mg dose, and 85.8% at the 240 mg dose as measured by whole blood testing compared with placebo. It was reduced by 40.4%, 70.%, and 68.9%, respectively, when measured by traditional testing.

Adverse events were similar in both the muvalaplin and placebo groups.

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Ruth Gimeno, vice president of Lilly’s diabetes and metabolism research group, said the company is considering its next steps toward late-stage trials.

“We will have to discuss with the regulators, but we are very excited,” she said in an interview.

She noted that although the drug has reduced cardiovascular risk factors, large trials are needed to prove that reducing Lp(a) actually reduces heart attacks and other adverse cardiovascular events. .

At the same meeting, London-based Silence Therapeutics reported 60-week results of its 180-patient Phase 2 trial of zerlasiran, which works by reducing LPA gene activity leading to Lp( a) high using a known technology. in the form of short interfering RNA, or siRNA.

A single injection of zerlasiran 300 mg or 450 mg every 16 or 24 weeks reduced Lp(a) by 80% to 85% during 36 to 60 weeks of follow-up with no major safety issues.

“We have seen a profound fallout, as we saw in Phase One,” Dr. Curtis Rambaran, the company’s chief medical officer, said in an interview. Silence will test the 300 mg dose in a late-stage trial that will begin mid-next year, he said.

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The results of both studies were published in JAMA.

Other injectable Lp(a) treatments in clinical trials include Lilly’s lepodisiran, Amgen’s olpasiran and Novartis’s pelacarsen.

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