Researchers at Brigham and Womens Hospital in Boston, MA have succeeded in markedly reducing the levels of bad cholesterol in patients suffering from cardiovascular disease in a clinical trial using the investigational drug Olpasiran.
Cardiovascular disease is the leading cause of death for people of most racial and ethnic groups in the United States and is reportedly costing the country over 200 billion dollars every year. Lipoprotein(a) is a type of bad cholesterol believed to contribute to the condition by building up under the inner lining of arteries and increasing the risk of atherosclerosis. However, as of right now, there are no pharmacological therapies to decrease its concentrations in the bloodstream approved by the FDA.
Reporting in The New England Journal of Medicine, scientists at Brigham and Women’s Hospital have conducted a phase II, randomized, placebo-controlled clinical trial of an investigational drug called Olpasiran in patients with established cardiovascular disease and known high blood concentrations of lipoprotein(a). Olpasiran is a small interfering RNA (siRNA) preventing the assembly of lipoprotein(a) in the liver leading to an overall decrease of the protein concentration in the bloodstream.
The trial included around 300 patients out of which three quarters received one of four doses of the drug and the rest a placebo. By the end of the trial the scientists were able to show that patients who received higher doses of Olpasiran had more than a 95% drop in lipoprotein(a) levels over 36 weeks compared to the placebo.
“These study results show that marked and sustained reduction of lipoprotein(a) is possible through RNA interference using olpasiran,” said Michelle O’Donoghue, M.D. , cardiovascular medicine specialist at Brigham and Women’s Hospital and senior author of the study in a press statement.
In a previous article published in Biomedicines discussing modern approaches in lowering lipoprotein(a) levels, Pelacarsen, an antisense oligonucleotide, is named as another promising candidate in treating cardiovascular disease. With a similar mode of action to Olpasiran, in a phase 2 clinical trial, the compound was shown to reduce lipoprotein(a) levels by 80%.
Despite the successful reduction in lipoprotein(a) levels in the Olpasiran trial, the scientists say that more and larger trials will be necessary to determine the drug’s efficacy in treating cardiovascular disease in the long haul. The researchers add that a limitation for future research is the lack of a clear threshold for an ´abnormal´ lipoprotein(a) concentration due to it being genetically driven leading to a large variation in its distribution across patients.
Concluding in a press statement O’Donoghue said that “These findings set the stage for a much larger phase III 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.”