A little more than a month after AstraZeneca jumped into the fray with the purchase of a rival heart drug candidate, Eli Lilly is turning up the heat on the drugmakers’ potential lipoprotein showdown.
Across three doses tested in a phase 2 study, Lilly’s lipoprotein (a) (Lp(a)) inhibitor muvalaplin helped significantly reduce patients’ heightened levels of Lp(a)—a genetic risk factor for heart disease—versus placebo, allowing the trial to meet its primary endpoint.
The drug, which is taken orally once a day, also met secondary endpoints across each of the 10-mg, 60-mg and 240-mg doses tested, Lilly said in a release.
Muvalaplin is designed to disrupt the formation of Lp(a) by blocking the initial interaction between apolipoprotein(a) (apo(a)) and apolipoproteinB (apoB).
Lilly estimates that about 20% of people in the U.S., or 63 million individuals, deal with high levels of Lp(a), which can greatly increase the risk of heart attack and lead to other cardiovascular risks.
To interpret the muvalaplin results, Lilly used both an intact Lp(a) assay and an apo(a) assay.
At the study’s 12-week mark, patients experienced placebo-adjusted Lp(a) reductions of 47.6%, 81.7% and 85.8% on the 10-mg, 60-mg and 240-mg muvalaplin doses, respectively, according to the intact Lp(a) assay.
For the apo(a) assay, the respective Lp(a) reductions on those same doses clocked in at 40.4%, 70% and 68.9%.
On the trial’s secondary endpoints, muvalaplin at all three doses hit statistical significance for meeting Lp(a) thresholds, triggering apoB reductions and more, Lilly added in its release.
While current cholesterol-lowering therapies aren’t approved to curb patients’ Lp(a) levels, other injectable efforts targeting lipoprotein(a) are progressing through the clinic, with Lilly itself working on one such candidate named lepodisiran.
In the late-stage ACCLAIM-Lp(a) trial, Lilly is looking at how lepodisiran fares against placebo at cutting major cardiovascular events in patients with elevated Lp(a) who have established atherosclerotic cardiovascular disease or who are at risk for their first cardiovascular event.
Elsewhere, AstraZeneca last month shelled out $100 million for CSPC Pharmaceutical Group’s preclinical heart disease candidate YS2302018. Like Lilly’s muvalaplin, the prospect AZ has acquired is also an oral Lp(a) disrupter.
Eyeing the candidate’s ability to prevent Lp(a) formation, AZ has pinned its hopes on the small molecule’s potential to benefit people with dyslipidemia, a condition defined by high levels of fat in the blood.
Overall, AZ aims to develop YS2302018 both on its own and in combination with other assets like its PCSK9 inhibitor AZD0780.