Lilly pill cuts genetic form of cholesterol nearly 86% in study

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

The drug, muvalaplin, reduced levels of lipoprotein(a), or Lp(a), by 70% using a traditional blood test and by nearly 86% based on a more specific test developed by the company, researchers reported at the American Heart Association meeting in Chicago.

Lilly's drug is the only oral treatment in a field of several injectable therapies being tested to treat high Lp(a), a risk factor for heart disease that affects one in five individuals globally.

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

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

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

Muvalaplin reduced Lp(a) by 47.6% at 10 mg, 81.7% at 60 mg and 85.8% on 240 mg as measured by the intact blood test versus placebo. It was reduced by 40.4%, 70.0%, and 68.9%, respectively, as measured by the traditional test.

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

Ruth Gimeno, Lilly's group vice president for diabetes and metabolic research, said the company is weighing next steps for advancing to late-stage trials.

"We'll have to have discussions with regulators, but we're very excited," she said in an interview.

She noted that while the drug has reduced a cardiovascular risk factor, large trials are needed to prove lowering Lp(a) actually cuts heart attacks and other adverse cardiovascular events.

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

A 300 mg or 450 mg injection of zerlasiran given 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 saw profound knockdown, as we saw in the 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 set to start in the middle of next year, he said.

Results of both studies were published in JAMA.

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