Lilly’s muvalaplin is the first oral drug to show positive Phase II findings for Lp(a) reduction, eliciting up to an 86% drop in the biomarker after 12 weeks.
Eli Lilly on Monday unveiled Phase II data for its investigational pill muvalaplin, touting substantial reductions in lipoprotein(a) levels in adults at risk of adverse cardiovascular events.
At 12 weeks, 240 mg of muvalaplin elicited an 85.8% reduction in lipoprotein(a) [Lp(a)] concentration versus placebo, as measured by an intact Lp(a) assay. Lower doses also proved to be better than placebo, with 60-mg muvalaplin cutting Lp(a) by 81.7% and the 40 mg dose triggering a 47.6% decrease, Lilly reported. High Lp(a) is an inherited risk factor for heart disease for which there are currently no approved pharmaceutical interventions. According to the American Heart Association, about one out of every five people worldwide has high Lp(a).
Muvalaplin also aced all secondary endpoints in the mid-stage study. More than 95% of patients given the 60-mg and 240-mg doses reached Lp(a) levels lower than 125 nmol/L after 12 weeks, whereas only 6% of placebo comparators hit this threshold. Meanwhile, apolipoprotein(B)—another cardiovascular risk biomarker—was also reduced across all muvalaplin doses.
These results represent the “first positive Phase 2 data for an oral approach,” Ruth Gimeno, group vice president of Diabetes and Metabolic Research at Lilly Research Laboratories, said in a statement, adding that the company is currently “exploring next steps” for the drug. In an interview with Reuters, Gimeno noted that the pharma will still need to discuss muvalaplin’s path forward with regulators, “but we’re very excited.”
“We believe that muvalaplin has megablockbuster potential if the drug delivers positive primary prevention outcomes, which will take several years to study,” wrote Leerink Partners’ David Risinger in an investor note.
Lp(a) is a type of low-density lipoprotein (LDL) cholesterol that is often linked to residual cardiovascular risk in patients with atherosclerotic cardiovascular diseases despite adequate LDL control. Structurally, Lp(a) consists of apolipoprotein(a) and apolipoprotein(B) molecules covalently bound together. According to the Centers for Disease Control and Prevention, patients with elevated Lp(a) levels are at elevated risk of stroke, aortic stenosis and heart attacks.
Muvalaplin is an oral small molecule drug that interferes with the covalent bond between apolipoprotein(a) and apolipoprotein(B). This mechanism of action allows muvalaplin to prevent the formation of Lp(a).
With muvalaplin, Lilly is paving the way to the first oral Lp(a) therapy, seeking to differentiate itself in a space that is dominated by injectable treatments. The pharma itself, for instance, is also developing lepodisiran, a subcutaneous RNA silencer that in November 2023 demonstrated in a Phase I study.
Ahead of it in the RNA silencing field is Amgen, which is developing the siRNA therapeutic olpasiran, currently being tested in a Phase III trial of patients with atherosclerotic cardiovascular disease.
Meanwhile, following in Lilly’s footsteps is AstraZeneca, which last month bet up to $2 billion on CSPC Pharmaceutical Group’s preclinical candidate YS2302018, which is also orally available and is designed to block the formation of Lp(a).
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