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Novel Small RNA Interference Therapy to Reduce Lipoprotein(a)-Mediated Cardiovascular Risk

Lipoprotein(a), a low-density lipoprotein, is a biomarker for atherosclerotic cardiovascular disease. Currently, there are no approved treatments to treat elevated levels of lipoprotein(a). New treatment approaches are emerging in the field of lipid-lowering therapy through gene silencing methods.

Olpasiran, a Small Interfering RNA

Olpasiran is an investigational drug that reduces lipoprotein(a) concentration by degrading the RNA that codes for a protein that is an essential part of the molecule.


Researchers at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, conducted a phase 2, randomized, placebo-controlled clinical trial of olpasiran in patients with established cardiovascular disease to evaluate its safety and tolerability and to identify an optimal dose of olpasiran for reducing lipoprotein(a) levels. The trial included 227 patients who received one of four doses of olpasiran and 54 who received a placebo. They found that patients who received higher doses of olpasiran had more than a 95% drop in lipoprotein(a) over 36 weeks compared to placebo. The treatment was not associated with serious side effects apart from occasional injection site swelling and related mild reactions.

Small RNA Interference Therapy

“These study results show that marked and sustained reduction of lipoprotein(a) is possible through RNA interference using olpasiran,” said lead author Michelle O’Donoghue, M.D., MPH, Cardiovascular Division, Brigham and Women’s Hospital. “These findings set the stage for a much larger phase 3 trial to definitively evaluate if lowering lipoprotein(a) translates into better outcomes. Olpasiran is a very promising therapy for individuals with high lipoprotein(a) levels who currently do not have any effective therapies to lower its concentration.”



Source: Eurekalert

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