At the European Society of Cardiology (ESC) conference in Amsterdam, Amgen unveiled the Phase II clinical data for Olpasiran, a small interfering RNA (siRNA) that is being developed to reduce Lp(a) in patients with cardiovascular disease (CVD). In 2022, OCEAN (a)-DOSE Phase II showed that Olpasiran reduced Lp(a) levels in patients by 95%. This study, which resulted from the off-treatment extension period, showed that patients taking 75mg of Olpasiran previously every 12 weeks presented a 40%–50% reduction in LP(a) for nearly a year after their last dose. The drug is expected to reach $1.05bn in sales by 2029, according to GlobalData.
Lp(a) is an atherogenic particle and an independent predictor of CV risk. Elevated levels of Lp(a) in the blood are considered a risk factor for CVD, including heart attack and stroke, as it promotes the formation of blood clots and plaque buildup in the arteries. At present, there are no specific therapies that target Lp(a) directly on the market. The standard treatments for dyslipidemia, such as statins and other cholesterol-lowering drugs, are not effective in reducing Lp(a) levels. Therefore, there is a high level of unmet need for therapies targeting other lipid particles, particularly the Lp(a) particle. However, there are a few strategies that have been shown to lower Lp(a) levels, including niacin, Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, antisense oligonucleotides, and lifestyle modifications. Niacin is a B-vitamin that has been shown to reduce Lp(a) levels by up to 30%. However, niacin can have side effects such as flushing and liver damage, so it is not used as frequently as it once was. PCSK9 inhibitors are a newer class of drugs that have also been shown to lower Lp(a) levels by up to 30%. However, they are expensive and typically reserved for patients who cannot tolerate statins or who have very high cholesterol levels. Antisense oligonucleotides target the genetic material responsible for producing Lp(a). They have shown promise in early clinical trials and have been shown to reduce Lp(a) levels by up to 90%. But, more research is needed to determine their safety and effectiveness in larger populations. Lifestyle modifications may not specifically target Lp(a) but exercise, weight loss, and a healthy diet can help improve overall cardiovascular health and lower the risk of heart disease.
Olpasiran is a promising drug treatment for dyslipidemia and works by preventing the assembly of Lp(a) and therefore the translation of the apo(a) protein, hence reducing Lp(a) in the circulation. Amgen is currently enrolling patients for a Phase III study.