THOUSAND OAKS, Calif., March 23, 2018 — Amgen (NASDAQ:AMGN) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion to include a new indication in the Repatha® (evolocumab) label for adults with established atherosclerotic cardiovascular disease (myocardial infarction, stroke or peripheral arterial disease) to reduce cardiovascular risk by lowering LDL-C levels. The recommended label recognizes the positive findings from the Repatha cardiovascular outcomes study (FOURIER) and includes data on the additional reduction and prevention of heart attacks, strokes and coronary revascularizations on top of maximally tolerated statin therapy.
The Repatha cardiovascular outcomes study showed reductions in the risk of heart attack by 27 percent, the risk of stroke by 21 percent and the risk of coronary revascularization procedures by 22 percent in patients treated with Repatha and statin therapy compared to patients treated with placebo and statin therapy over a mean duration of 26 months.
"We welcome the CHMP's positive opinion to incorporate a new indication for adults with cardiovascular disease into the European label, recognizing the impact of Repatha to prevent life-changing events such as heart attacks and strokes," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "With the FOURIER outcomes data now included in the U.S. label and an anticipated label update in Europe in the coming months, we will continue to work with payers globally to ensure access to medication for higher-risk patients. Furthermore, we value and support the efforts by many stakeholders, including clinicians, advocates and payers, as we all work to reduce barriers to access and increase affordability for patients who need PCSK9 treatment."
The CHMP's positive opinion will now be reviewed by the European Commission (EC), which has the authority to approve medicines for the European Union (EU). If approved, the centralized European marketing authorization for Repatha will be updated to include the new indication. Norway, Icelandand Liechtenstein, as members of the European Economic Area (EEA), will take corresponding decisions on the basis of the EC's decision.
On Dec. 1, 2017, the U.S. Food and Drug Administration (FDA) approved a new indication for Repatha as the first PCSK9 inhibitor to prevent heart attacks, strokes and coronary revascularizations in adults with established cardiovascular disease following a priority review of Amgen's supplemental Biologics License Application.
Repatha Cardiovascular Outcomes (FOURIER) Study: Key Outcomes
The 27,564-patient Repatha cardiovascular outcomes study (FOURIER) demonstrated that adding Repatha to optimized statin therapy resulted in a statistically significant 20 percent (p<0.001) reduction in major adverse cardiovascular events (MACE) represented in the key secondary composite endpoint of time to first heart attack, stroke or cardiovascular death. The study found a statistically significant 15 percent reduction (p<0.001) in the risk of the primary composite endpoint, which included hospitalization for unstable angina, coronary revascularization, heart attack, stroke or cardiovascular death.
The magnitude of risk reduction in both the primary and key secondary composite endpoints grew over time, with the robust benefit starting as early as six months and accruing through the median 2.2 years of the study.
Patients on Repatha experienced a reduction in the risk of heart attack (27 percent, nominal p<0.001), stroke (21 percent, nominal p=0.01) and coronary revascularization (22 percent, nominal p<0.001). Consistent with recent trials of more intensive LDL-C lowering, there was no observed effect on cardiovascular mortality. Similarly, there was no observed effect on hospitalization for unstable angina.
The safety profile of Repatha in the outcomes trial was generally consistent with the safety profile for the 12- and 52-week controlled trials involving patients with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH).
Repatha Cardiovascular Outcomes (FOURIER) Study Design
FOURIER (Further Cardiovascular OUTcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), a multinational Phase 3 randomized, double-blind, placebo-controlled trial, is designed to evaluate whether treatment with Repatha in combination with high- or moderate-intensity statin therapy compared to placebo plus statin therapy reduces cardiovascular events. The hard MACE composite endpoint is the time to cardiovascular death, myocardial infarction or stroke (key secondary endpoint). The extended MACE composite endpoint is the time to cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina or coronary revascularization (primary endpoint).
Eligible patients with high cholesterol (LDL-C ≥70 mg/dL or non-high-density lipoprotein cholesterol [non-HDL-C] ≥100 mg/dL) and established cardiovascular disease at more than 1,300 study locations around the world were randomized to receive Repatha subcutaneous 140 mg every two weeks or 420 mg monthly plus high- or moderate-intensity effective statin dose; or placebo subcutaneous every two weeks or monthly plus high- to moderate-intensity statin dose. Statin therapy was defined in the protocol as at least atorvastatin 20 mg or equivalent daily with a recommendation for at least atorvastatin 40 mg or equivalent daily where approved. The study was event driven and continued until at least 1,630 patients experienced a key secondary endpoint.
About Repatha® (evolocumab)
Repatha® (evolocumab) is a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). Repatha binds to PCSK9 and inhibits circulating PCSK9 from binding to the low-density lipoprotein (LDL) receptor (LDLR), preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface. 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.
Repatha is approved in more than 60 countries, including the U.S., Japan, Canada, and in all 28 countries that are members of the European Union. Applications in other countries are pending.