Eli Lilly and Company (Lilly) has announced positive Phase 2 results for muvalaplin, an investigational, once-daily oral treatment targeting lipoprotein(a) [Lp(a)], a genetic risk factor for heart disease.
The trial compared three daily doses of muvalaplin, 10mg, 60mg, and 240mg, against a placebo in 233 adults with high Lp(a) levels. Lp(a) levels were tested using both a traditional blood test and a new method that measures intact Lp(a) particles.
The study showed that the highest dose of muvalaplin significantly reduced elevated Lp(a) levels in adults, meeting its primary endpoint of Lp(a) reduction from baseline to week 12.
At the 12-week primary endpoint, muvalaplin showed significant reductions in Lp(a) levels compared to placebo.
Placebo-adjusted reductions reached up to 85.8% using the intact Lp(a) assay and up to 70% using the apo(a) assay.
Muvalaplin also met its secondary endpoints for all doses. Each dose achieved statistical significance for Lp(a) reduction, while the 60mg and 240mg doses also showed significant reductions in apoB levels.
Furthermore, adverse events were similar between the muvalaplin and placebo groups, Lilly said.
The incidence of adverse events leading to study drug discontinuation ranged from 0% to 8.8% across treatment groups, with single events spread across various system organ classes. No deaths were reported during the study.
Lilly research laboratories diabetes and metabolic research group vice president Ruth Gimeno said: “While injectable approaches for Lp(a) are currently in Phase 3 development, including Lilly’s own lepodisiran programme, these are the first positive Phase 2 data for an oral approach.
“We are very pleased to see these promising results and look forward to further exploring next steps for muvalaplin.”
While muvalaplin reduced a key cardiovascular risk factor, large trials are needed to confirm that lowering Lp(a) reduces heart attacks and other adverse cardiovascular events, Gimeno said.
In a similar development, London-based Silence Therapeutics reported 60-week results from a 180-patient Phase 2 trial of zerlasiran, which reduces Lp(a) levels by targeting the LPA gene with short interfering RNA (siRNA).
A 300mg or 450mg injection of zerlasiran, given every 16 or 24 weeks, reduced Lp(a) by 80% to 85% over 36 to 60 weeks of follow-up, with no major safety concerns.
