Amgen presented new compelling data from the Phase 3 FOURIER open label extension (OLE) studies of Repatha (evolocumab) in adults with atherosclerotic cardiovascular disease (ASCVD) during the Aug. 29 late-breaking Hot Line Session of the European Society of Cardiology (ESC) Annual Meeting being held in Barcelona, Spain, and online. These data were simultaneously published in Circulation. Repatha is the first and only proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) to date to show long-term clinical outcomes in patients with ASCVD for up to 8.4 years.1
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The FOURIER-OLE studies evaluated 6,635 patients from the FOURIER parent study (3,355 initially randomized to Repatha and 3,280 to placebo) from the U.S. and Europe.1 The studies were designed to assess the long-term safety and tolerability of Repatha in adults with clinically evident ASCVD for a median follow up of up to five years and a maximum exposure to Repatha of more than eight years when parent and extension studies were combined. No new long-term safety findings were observed.1
The OLE studies showed Repatha delivered medically significant and sustained reduction in low-density lipoprotein cholesterol (LDL-C) levels, with 80% of patients achieving a low-density lipoprotein cholesterol (LDL-C) level of <55mg/dL.1 Additionally, the LDL-C reduction of 58% from baseline was consistent over long-term follow up (week 260) on Repatha. An additional prespecified exploratory analysis in the OLE studies showed a lower rate of major adverse cardiovascular events, including cardiovascular death, in patients originally randomized to Repatha (20% relative risk reduction [RRR] for major cardiovascular events and 23% RRR for cardiovascular death) versus those originally randomized to placebo in the parent FOURIER study.1
“The new findings from the FOURIER-OLE studies confirm that earlier initiation of Repatha, combined with longer duration of treatment, has the potential to deliver a greater reduction in cardiovascular risk, including death,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen. “These data add to the robust body of evidence for Repatha, demonstrating that long-term treatment with Repatha is well tolerated in patients with stable ASCVD.”
“These findings fill a significant gap in the body of research on the long-term safety and efficacy of PCSK9 inhibitors,” said Michelle L. O’Donoghue M.D., MPH, senior investigator, TIMI Study Group at Brigham and Women’s Hospital and Lead FOURIER-OLE Trial Investigator. “Importantly, earlier initiation of LDL-C lowering with evolocumab combined with consistent long-term use, further reduced the risk of major cardiovascular events and cardiovascular mortality in this study.”
Cardiovascular disease (CVD) remains the leading cause of global mortality and a major contributor to disability and rising healthcare costs.2,3 In the U.S., someone suffers a heart attack every 40 seconds.4 Given systemic barriers in the U.S. healthcare system, only 3.2% of an estimated 18.7 million U.S. adults with ASCVD were actually taking an add-on lipid-lowering therapy, despite treatment being recommended to 61.4%.5 Further, patients with ASCVD whose prescription for a PCSK9i was rejected had an 11% higher risk of having a cardiovascular event such as a heart attack or stroke within a year