Muvalaplin for lowering Lp(a) succeeds in early-phase trial

The selective small molecule inhibitor of lipoprotein(a) (Lp[a]) formation muvalaplin helps reduce Lp(a) levels by up to 65 percent without safety and tolerability signals, as shown in the results of a phase I trial.

The trial included 114 participants who were assigned to either the single-ascending dose group (n=55, mean age 29 years, 64 percent women, 91 percent White) or the multiple-ascending dose group (n=59, mean age 32 years, 58 percent women, 80 percent White). Muvalaplin was administered orally as single ascending doses ranging from 1 mg to 800 mg in the single-ascending dose group (healthy adults with any Lp[a] level), and as multiple ascending doses ranging from 30 mg to 800 mg in the multiple-ascending dose group (patients with Lp[a] ≥30 mg/dL). Treatment was given for 14 days.

No tolerability concerns or clinically significant adverse effects arose during muvalaplin treatment. Oral doses of 30–800 mg for 14 days led to increases in muvalaplin plasma concentrations, with half-life ranging from 70 to 414 hours.

Lp(a) plasma levels decreased within 24 hours after the first dose, with further reduction on repeated dosing. Maximum placebo-adjusted Lp(a) reduction was between 63 percent and 65 percent, with plasma Lp(a) levels <50 mg/dL in 93 percent of participants.

Similar effects were noted at daily doses of 100 mg or more. There were no clinically significant changes in plasminogen levels or activity recorded.