Clinical trial finds novel therapy markedly reduced lipoprotein(a) levels in people with cardiovascular disease

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. 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.

Lipoprotein(a) is a special type of bad cholesterol that is believed to contribute to heart disease, but there are no approved pharmacological therapies to decrease its concentration in the bloodstream. 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.

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.

“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, MD, 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 don’t have any effective therapies to lower its concentration.”

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Materials provided by Brigham and Women’s Hospital. Note: Content may be edited for style and length.

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