New Data From Trials of Evolocumab, Olpasiran Show Promise for Cardiovascular Disease Care
Patients with atherosclerotic cardiovascular disease who were already receiving statin therapy had a reduction in adverse cardiovascular outcomes with earlier initiation of evolocumab.
New data from the FOURIER and FOURIER-OLE studies of evolocumab (Repatha; Amgen) as well as the phase 2 OCEAN(a)-DOSE study of olpasiran (Amgen) showed promise in the treatment of cardiovascular disease, according to results presented at the American College of Cardiology 2023 Scientific Session.1
The data for evolocumab evaluated all primary endpoint events from patients enrolled in the parent FOURIER study, with a median follow-up of 2.2 years, and for patients in the FOURIER-OLE study for an additional 3 years of follow up. Evolocumab is a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). By inhibiting the binding of PCSK9 to low-density lipoprotein receptors (LDLRs), it increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels.1
According to the trial results, over the duration of follow-up, patients with atherosclerotic cardiovascular disease (ASCVD) who were already receiving statin therapy had a reduction in adverse cardiovascular outcomes with earlier initiation of evolocumab. This was shown by a reduction in total cardiovascular endpoint events (cardiovascular disease, myocardial infarction, stroke, unstable angina, or coronary revascularization) in patients who had initiated treatment with evolocumab in the parent study and continued it in the OLE, compared to those in the standard of care group in the parent study who only initiated evolocumab during the OLE.1
“The robust body of evidence on Repatha continues to underscore its clinical importance as a transformative therapy in lowering LDL-C to reduce [cardiovascular] events like heart attack and stroke in patients with ASCVD,” said David M. Reese, MD, executive vice president of Research and Development at Amgen, in a press release.1
A new analysis from the OCEAN(a) Dose study also showed the promise of olpasiran, an investigational small interfering RNA-based therapy that has been shown to reduce lipoprotein(a) by more than 90% in the phase 2 trial. The new analysis examined whether the percentage of lipoprotein(a) reduction with olpasiran is affected by baseline lipoprotein(a) concentrations.1
OCEAN(a)-DOSE is a randomized, placebo-controlled dose-finding study of olpasiran in 281 patients with established ASCVD and lipoprotein(a) levels >150 nmol/L. Patients were randomized to 1 of 4 doses—olpasiran at 10 mg Q12 weeks, 75 mg Q12 weeks, 225 mg Q12 weeks or 225 mg Q24 weeks—or placebo, administered subcutaneously. The study evaluated the safety, tolerability, and optimal dosing for olpasiran in adults with established ASCVD to lower lipoprotein(a).
Lipoprotein(a) is an independent risk factor for cardiovascular disease. The median baseline lipoprotein(a) concentration was 260.3 nmol/L throughout the treatment groups.2
Patients administered 75 mg or higher every 12 weeks had a 95% or greater reduction in lipoprotein(a) compared to placebo at week 36. For these doses, more than 98% of patients achieved an lipoprotein(a) level of 125 nmol/L or less at week 36.
According to the study, the results showed that olpasiran markedly reduced lipoprotein(a) concentration regardless of baseline level in those with ASCVD and lipoprotein(a) greater than 150 nmol/L.
At week 36 of the study, lipoprotein(a) increased by a mean of 3.6% in the placebo cohort compared with substantial reductions of lipoprotein(a) levels across all the olpasiran arms. The placebo-adjusted mean percent reductions were 70.5% for 10 mg every 12 weeks, 97.4% for 75 mg every 12 weeks, 101.1% for 225 mg every 12 weeks and 100.5% for 225 mg every 24 weeks.2
The findings provide important new insights into how much lipoprotein(a) reduction can be achieved with olpasiran in settings where the lipoprotein(a) burden is very high.1
REFERENCE
1. Amgen to Present New Repatha (Evolocumab) and Olpasiran Data at ACC. News release. Amgen; March 1, 2023. Accessed March 4, 2023. https://www.amgen.com/newsroom/press-releases/2023/03/amgen-to-present-new-repatha-evolocumab-and-olpasiran-data-at-acc
2. Murphy, J. Treatment With Olpasiran Significantly Lowers Lipoprotein(A) Levels. Pharmacy Times. Published November 22, 2022. Accessed March 4, 2023. https://www.pharmacytimes.com/view/treatment-with-olpasiran-significantly-lowers-lipoprotein-a-levels.
