Muvalaplin

At a medical meeting on Monday, Eli Lilly presented data from a study showing that its experimental drug muvalaplin significantly reduced levels of inherited high cholesterol in a mid-stage trial. Researchers reported at an American Heart Association meeting in Chicago that the drug muvalaplin was able to reduce lipoprotein (a) or Lp(a) levels by 70 percent with a traditional blood test and by nearly 86 percent with a more specific test developed by the company. Lilly's drug is currently the only oral treatment, while several injectable therapies are currently being tested to treat high lipoprotein (a), a risk factor for heart disease in one in five people worldwide. Unlike low-density lipoprotein (LDL), this so-called bad cholesterol can be treated with diet and statins, while Lp(a) currently has no approved treatment and few people are aware they have it. Elevated lipoprotein (a) significantly increases the risk of heart attack, stroke, aortic stenosis, and peripheral artery disease (fatty plaque buildup in the arteries), especially in people of African and South Asian descent. The trial compared the effects of three daily doses of muvalaplin (10,60 and 240 mg) with placebo in 233 adults with high levels of Lp(a). The researchers used a traditional blood test and a new method to measure intact Lp(a) particle levels in the blood to test for Lp(a) levels. Compared with placebo, 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. Compared with traditional methods, the results were reduced by 40.4%, 70.0% and 68.9%, respectively. The rates of adverse events were similar in the muvalaplin and placebo groups. Ruth Gimeno, Eli Lilly's group vice president for diabetes and metabolic research, said the company is considering moving the drug into late-stage trials. "We need to have discussions with regulators, but we're very excited about it," she said in an interview. She stressed that although the drug reduced cardiovascular risk factors, a large number of trials are still needed to prove that lowering lipoprotein (a) levels actually reduces heart attacks and other adverse cardiovascular events. At the same meeting, London-based Silence Therapeutics reported results from a 60-week phase II trial of zerlasiran in 180 patients. zerlasiran inhibits LPA gene activity through short interfering RNA (siRNA) technology, resulting in high levels of Lp(a). Injections of 300 mg or 450 mg of zerlasiran every 16 or 24 weeks resulted in an 80 to 85 percent reduction in Lp(A) over a follow-up period of 36 to 60 weeks with no significant safety concerns. Dr. Curtis Rambaran, the chief medical officer of Silence Therapeutics, saidin an interview, "We observed significant reductions to the same extent as in the Phase 1 trial." Silence Therapeutics plans to test a 300-milligram dose in a late-stage trial that will begin in the middle of next year, he noted. The results of both studies were published in the Journal of the American Medical Association. Other injectable Lp(a) treatments in clinical trials include Eli Lilly's lepodisiran, Amgen's olpasiran and Novartis' pelacarsen.

Yesterday, Eli Lilly and Company revealed promising Phase 2 results for its investigational small molecule drug, Muvalaplin, against cardiovascular events. The drug met its primary and secondary endpoints at 12 weeks, revealing a reduction of lipoprotein(a)–  Lp(a)– levels by up to 85% in adults with high risk for cardiovascular events. Muvalaplin selectively inhibits Lp(a), a genetic risk factor for heart disease. In the U.S., about 63 million people are known to have high levels of Lp(a). Lp(a) can form plaques in the walls of blood vessels, disrupting blood flow to essential organs, including the heart, kidneys, lungs, and brain. An excessive accumulation of Lp(a) plaques can result in heart attack, stroke, or other cardiovascular diseases. Eli Lilly’s Muvalaplin blocks the interaction between apolipoprotein(a) and apolipoprotein B, preventing the formation of Lp(a), and thereby lowering the risk of cardiovascular diseases. "High levels of Lp(a) have been shown to be a significant risk factor for atherosclerotic cardiovascular disease, affecting over one billion adults globally," explained Stephen J. Nicholls, Director of the Victorian Heart Hospital and Institute, and Professor of Cardiology at Monash University, Australia, in a press release. "Current cholesterol-lowering therapies are not approved to lower Lp(a) levels, highlighting an unmet need for people living with cardiovascular disease. These data represent a needed scientific advancement with the potential to reduce the risk of cardiovascular events such as heart attacks or strokes with a once-daily pill." googletag.cmd.push(function () { googletag.display('text-ad1'); }); In the Phase 2 study, Muvalaplin was given to participants in three different dosages– 10mg, 60mg, and 240mg– and tested against a placebo. At all dosages, Muvalaplin showed a reduction of Lp(a) levels compared to the placebo. The researchers measured the reductions using an Lp(a) assay– up to 85.8% Lp(a) reduction– and an apolipoprotein(a) assay– up to 70% Lp(a) reduction– at the highest dosage. "While injectable approaches for Lp(a) are currently in Phase 3 development, including Lilly's own lepodisiran program, these are the first positive Phase 2 data for an oral approach," said Ruth Gimeno, Group Vice President of Diabetes and Metabolic Research at Lilly Research Laboratories, in a press release. "We are very pleased to see these promising results and look forward to further exploring next steps for Muvalaplin." Cardiovascular disease treatments have seen a major surge in interest from big pharma companies. Just recently, AstraZeneca entered into a licensing deal worth up to $2 billion ​ with the Chinese company CSPC Pharmaceutical Group to further develop its oral small molecule drug targeting Lp(a)– a rival to Lilly’s Muvalaplin.