In an early phase multicenter clinical study, large reductions in lipoprotein(a), or Lp(a), were achieved with a well-tolerated small interfering RNA (siRNA) therapeutic, lepodisiran.
The reductions in serum Lp(a) in patients receiving lepodisiran were dose dependent but adverse events were not, said Steven E. Nissen, MD, professor of medicine at the Lerner College of Medicine at Cleveland Clinic, Cleveland, Ohio.
Rather, drug-related adverse events "were uncommon and generally similar across all lepodisiran doses and the placebo group," reported Nissen, who pointed out that safety and tolerability were the primary endpoints and purpose of this phase 1 study.
Lp(a) Strongly Associated With CV Risk
Similar to low-density lipoprotein cholesterol (LDL-C), elevated levels of serum Lp(a) have been associated with major adverse cardiac events (MACE). In a 2022 review article that summarized pathophysiological, observational, and genetic studies, Lp(a) was found to be implicated in vascular inflammation, atherogenesis, calcification, and thrombosis.
Furthermore, Lp(a) has been associated with residual risk of cardiovascular (CV) events even after tight control of other risk factors, including elevated LDL-C, Nissen said.
So far, no well-tolerated therapy has been found to be effective for reducing Lp(a), but siRNA is a novel and attractive approach, according to Nissen, who presented these results November 12 at the American Heart Association Scientific Sessions 2023.
