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CHMP Endorses Evolocumab for Prevention of Myocardial Infarction and Stroke in ASCVD Patients

Apr 01, 2018 20:30 CST Updated Mar 30, 15:22
Amgen

Developer of Treatment Drugs for Serious Diseases

Committee for Medicinal Products for Human Use

Committee for Medicinal Products for Human Use (CHMP)The Committee for Medicinal Products for Human Use (CHMP) is the committee within the European Medicines Agency (EMA) responsible for human medicines. The CHMP replaced the former Committee for Proprietary Medicinal Products (CPMP) in May 2004.The CHMP plays a vital role in the authorization of medicines in the European Union (EU). In the centralized procedure, the CHMP is responsible for: 1) conducting initial assessments of marketing authorization applications across the EU; assessing modifications or extensions to existing marketing authorizations (“variations”); considering recommendations from the Agency’s Pharmacovigilance Risk Assessment Committee regarding the safety of medicines on the market, and, where necessary, advising the European Commission to amend the marketing authorization of a medicinal product, or to suspend or withdraw it from the market.The CHMP also evaluates medicines authorized at the national level that are referred to the EMA, with the aim of maintaining a harmonized position throughout the EU.Furthermore, the CHMP and its working groups promote the development of medicines and pharmaceutical regulation by: providing scientific advice to companies researching and developing new medicines; developing scientific and regulatory guidelines to assist pharmaceutical companies in preparing marketing authorization applications for human medicines; and collaborating with international partners to harmonize regulatory requirements.

Oak Park, California, USA, recently– Amgen announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued an opinion on Repatha®A positive opinion was issued to add a new indication to the product label for (evolocumab), stating that Repatha can be used in adult patients with established atherosclerotic cardiovascular disease (myocardial infarction, stroke, or peripheral arterial disease) to reduce cardiovascular risk by lowering LDL-C levels. This update to the product label is based on the positive results from the Repatha Cardiovascular Outcomes Study (FOURIER). The label also includes data demonstrating that, when added to maximally tolerated statin therapy, Repatha provides additional reduction and prevention of myocardial infarction, stroke, and coronary revascularization.

Cardiovascular Outcomes Study of Evolocumab Shows: During a Mean Follow-Up of 26 Months, Patients Receiving Evolocumab and Statin Therapy Had a 27% Lower Risk of Myocardial Infarction, a 21% Lower Risk of Stroke, and a 22% Lower Risk of Coronary Revascularization Compared with Those Receiving Placebo and Statin Therapy.

Sean Harper, M.D., Executive Vice President of Research and Development at the Company, stated: “We welcome the CHMP’s addition of this new indication to the European product label, recognizing the role of evolocumab in preventing life-impacting events (such as myocardial infarction and stroke) in adult patients with cardiovascular disease.” Dr. Harper further noted: “The U.S. product label already includes data from the FOURIER study, and we anticipate that the European product label will be updated in the coming months. We will continue to collaborate with payers globally to ensure that high-risk patients have access to this treatment. Furthermore, we value and support the efforts of all stakeholders, including clinicians, advocates, and payers, to jointly reduce barriers to medication access for patients requiring PCSK9 inhibitor therapy, thereby making this treatment more affordable and accessible to a broader patient population.”

Currently, the European Commission (EC), which holds the authority to approve medicinal products in the European Union, will review the positive opinion issued by the Committee for Medicinal Products for Human Use (CHMP). If approved, the centralized marketing authorization for Repatha in Europe will include this new indication. Norway, Iceland, and Liechtenstein, as members of the European Economic Area (EEA), will make their respective decisions based on the EC’s resolution.

On December 1, 2017, the U.S. Food and Drug Administration (FDA) approved a new indication for evolocumab following priority review of the supplemental Biologics License Application submitted by Amgen. The approved indication allows the use of evolocumab in adult patients with established atherosclerotic cardiovascular disease to prevent myocardial infarction, stroke, and coronary revascularization. Evolocumab is the first PCSK9 inhibitor approved for this indication.

Evolocumab Cardiovascular Outcomes Study (FOURIER): Primary Results

The FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial, conducted in 27,564 patients, demonstrated that adding evolocumab to optimized statin therapy significantly reduced major adverse cardiovascular events (MACE), as reflected by the key secondary composite endpoint (time to first myocardial infarction, stroke, or cardiovascular death), by 20% (p<0.001). The study also found a significant 15% reduction in the risk of the primary composite endpoint (including hospitalization for unstable angina, coronary revascularization, myocardial infarction, stroke, or cardiovascular death) (p<0.001).

The magnitude of risk reduction for both the primary and key secondary composite endpoints increased over time, with robust benefits emerging as early as 6 months and continuing to accrue through 2.2 years (the median follow-up duration in the study).

Evolocumab reduces the risk of myocardial infarction by 27% (nominal p<0.001), stroke by 21% (nominal p=0.01), and coronary revascularization by 22% (nominal p<0.001) in patients with established atherosclerotic cardiovascular disease.1. This result is consistent with other studies on potent LDL-C lowering, and no effect on cardiovascular mortality was observed in this study. Similarly, no effect on hospitalization due to unstable angina was observed.2-6

The safety data for evolocumab in this study were largely consistent with the safety data from two other controlled studies (12 weeks and 52 weeks) in patients with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH).

Study Design of the Evolocumab Cardiovascular Outcomes Study (FOURIER)

FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) is a multinational, randomized, double-blind, placebo-controlled Phase 3 clinical study designed to evaluate whether Repatha, in combination with high-intensity or moderate-intensity statin therapy, further reduces cardiovascular events compared with placebo plus statin therapy. The key secondary endpoint of this study was the hard composite endpoint of major adverse cardiovascular events (MACE), defined as time to cardiovascular death, myocardial infarction, or stroke. The primary endpoint was the expanded MACE composite endpoint, defined as time to cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization.

This study was conducted with the participation of more than 1,300 research centers worldwide. Eligible patients with hyperlipidemia (LDL-C ≥ 70 mg/dL or non-high-density lipoprotein cholesterol [non-HDL-C] ≥ 100 mg/dL) and established cardiovascular disease were randomly assigned to receive either subcutaneous Repatha (140 mg every two weeks or 420 mg once monthly) in combination with high- or moderate-intensity statin therapy at effective doses, or subcutaneous placebo (every two weeks or once monthly) in combination with high- or moderate-intensity statin therapy. The protocol-mandated statin regimen consisted of at least 20 mg of atorvastatin daily or an equivalent dose, with a recommendation to use at least 40 mg of atorvastatin daily or an equivalent dose whenever permissible. This was an event-driven study, which continued until at least 1,630 patients experienced the key secondary endpoint.

Repatha®(Evolocumab) is a human monoclonal immunoglobulin G2 (IgG2) antibody targeting human proprotein convertase subtilisin/kexin type 9 (PCSK9). Repatha 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 recycle back to the hepatocyte surface. By inhibiting the binding of PCSK9 to LDLR, Repatha increases the number of LDLRs available to clear LDL from the bloodstream, thereby reducing LDL-C levels.7

Repatha has been approved in more than 60 countries and regions, including the United States, Japan, Canada, and all 28 member states of the European Union. Applications in other countries are currently underway.

About Repatha®(evolocumab)

Repatha®(Evolocumab) is a human monoclonal immunoglobulin G2 (IgG2) antibody targeting human proprotein convertase subtilisin/kexin type 9 (PCSK9). Repatha 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 recycle 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 reducing LDL-C levels.7

Repatha has been approved in more than 60 countries and regions, including the United States, Japan, Canada, and all 28 member states of the European Union. Applications in other countries are currently underway.

References

1. Sabatine MS, Giugliano RP, Keech AC, et al, for the FOURIER Steering Committee and Investigators. N Engl J Med. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. 2017;376:1713-22.

2. Cannon CP, et al. N Engl J Med. 2004;350:1495-1504.

3. LaRosa JC, et al. N Engl J Med. 2005;352:1425-1435.

4. ederson TR, et al. JAMA. 2005;294:2437-2445.

5. Search Collaborative Group. Lancet 2010;376:1658–69.

6. Cannon CP, et al. N Engl J Med. 2015;372:2387-2397.

7. Repatha® U.S. Prescribing Information. Amgen.

8. World Health Organization. Cardiovascular diseases (CVDs) fact sheet.
http://www.who.int/mediacentre/factsheets/fs317/en/. Accessed October 30, 2017.

Editor: Li Haili