Phase 3 HUYGENS Study Results Show Repatha® (evolocumab) Significantly Enhances Plaque Stability in Coronary Artery Disease Patients

Amgen recently announced at the 2021 European Society of Cardiology (ESC) Congress Repatha (Ruibaian), a novel cholesterol-lowering drug in the PCSK9 inhibitor class (^®, Generic Name: Generic Name: Evolocumab) Positive results from the Phase 3 HUYGENS study. Data showed: In patients with coronary artery disease (CAD), compared with optimized statin therapy alone, Repatha in combination with optimized statin therapy significantly improved plaque stability.

Heart attacks are typically the result of vulnerable plaque rupture. The primary characteristic of a vulnerable plaque is a large lipid core with a thin fibrous cap, which serves as a wall or barrier surrounding the plaque to maintain its integrity. The HUYGENS study evaluated whether, in addition to optimized statin therapy, treatment with Repatha could increase fibrous cap thickness, ultimately improving plaque stability.

The HUYGENS study met its primary endpoint: as measured by optical coherence tomography (OCT), Repatha in combination with optimized statin therapy significantly increased fibrous cap thickness compared with optimized statin therapy alone (increase: 42.7 μm vs. 21.5 μm; percent increase: 75% vs. 39%; p=0.01). Therefore, the addition of Repatha resulted in a twofold greater improvement in this feature compared with statin therapy alone. Repatha also improved all secondary endpoints of the study, including the reduction in maximum lipid arc as measured by OCT (-57.5° vs. -31.4°; p=0.01).

Results from a 52-week randomized, double-blind study in patients with acute coronary syndrome (ACS) receiving optimized statin therapy demonstrated that initiating Repatha within one week of an ACS event reduced LDL-C from 140 mg/dL to 28 mg/dL (–80%), whereas statin therapy alone reduced LDL-C from 142 mg/dL to 87 mg/dL (–39%). No new safety risks were identified. The most common treatment-emergent adverse events (>3%) were angina, myalgia, hypertension, diarrhea, fatigue, and cough.

Most acute coronary syndrome (ACS) events are caused by plaque rupture, and patients who have experienced a myocardial infarction are particularly susceptible to additional plaque ruptures, underscoring the importance of maintaining fibrous cap thickness to help stabilize plaques.

Plaque stability

Previous studies, including the GLAGOV study, have demonstrated that when added to optimized statin therapy, Repatha reduces plaque burden in patients with CAD by decreasing plaque volume. This is the first study to demonstrate that lowering LDL-C levels through PCSK9 inhibition reduces plaque burden.

The HUYGENS study demonstrated that, compared with optimized statin therapy alone, Repatha in combination with optimized statin therapy significantly improved a key feature of plaque stability in patients with CAD by increasing fibrous cap thickness. The HUYGENS study may provide mechanistic insights into the reduction in CV events observed in the FOURIER outcomes trial.

Although the HUYGENS study did not evaluate cardiovascular outcomes, its findings build upon a growing body of evidence that already supports the clinical profile of Repatha. The results of the HUYGENS study provide relevant insights into plaque biology and help demonstrate the important benefits of initiating Repatha therapy following a myocardial infarction. Fifty clinical trials, involving more than 47,000 patients randomized to Repatha or placebo, have demonstrated the clinical benefits of Repatha, including reductions in myocardial infarction and stroke, rapid (within 4 weeks) and long-term (mean 2.2 years) significant lowering of LDL-C, and a safety profile consistent with the FOURIER study over a 5-year treatment period.

Repatha is a human monoclonal immunoglobulin G2 (IgG2) antibody directed against human proprotein convertase subtilisin/kexin type 9 (PCSK9). The drug binds to PCSK9, inhibiting the binding of circulating PCSK9 to low-density lipoprotein (LDL) receptors (LDLR), thereby preventing PCSK9-mediated LDLR degradation and allowing LDLRs to be recycled back to the surface of hepatocytes. By inhibiting the binding of PCSK9 to LDLR, Repatha increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels.

To date, Repatha has been approved in 76 countries and regions, including the United States, Japan, China, and all 27 member states of the European Union. Applications in other countries are currently underway.

In China, Repatha (Ruibai'an^®，Generic name: Generic name: evolocumab, evolocumab）was first approved in August 2018, becoming the first PCSK9 inhibitor for the treatment of homozygous familial hypercholesterolemia (HoFH) in adults and adolescents aged 12 years and older. In January 2019, Repatha was approved for a new indication: to reduce the risk of myocardial infarction, stroke, and coronary revascularization in adult patients with atherosclerotic cardiovascular disease (ASCVD). This approval makes Repatha the first PCSK9 inhibitor available for this indication in the Chinese market.

Note: The original text has been abridged.

Original Source: New Data At ESC Congress 2021 Shows Repatha® (evolocumab) Improves Features Of Plaque Stability In Patients With Acute Coronary Syndrome (ACS)

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