Type of information: Positive opinion for the granting of a Market Authorisation in the EU
Product name: Repatha®
Therapeutic area: Rare diseases - Cardiovascular diseases
- monoclonal antibody/RNAi/PCSK9 inhibitor. Evolocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9).PCSK9 is a protein that targets LDL receptors for degradation and thereby reduces the liver's ability to remove LDL-C, or "bad" cholesterol, from the blood.Evolocumab, being developed by Amgen scientists, is designed to bind to PCSK9 and inhibit PCSK9 from binding to LDL receptors on the liver surface. In the absence of PCSK9, there are more LDL receptors on the surface of the liver to remove LDL-C from the blood.
Company: Amgen (USA - CA)
- adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (CVD), who require additional lowering of low density lipoprotein cholesterol (LDL-C), patients with homozygous familial hypercholesterolemia (HoFH) who require additional lowering of LDL-C
- established atherosclerotic cardiovascular disease
- • On March 22, 2018, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive
opinion recommending a change to the terms of the marketing authorisation for Repatha®. The CHMP adopted a new indication as follows:
- “Established atherosclerotic cardiovascular disease
Repatha® is indicated in adults with established atherosclerotic cardiovascular disease (myocardial infarction, stroke or peripheral arterial disease) to reduce cardiovascular risk by lowering LDL-C levels, as an adjunct to correction of other risk factors:
- • in combination with the maximum tolerated dose of a statin with or without other lipidlowering therapies or,
- • alone or in combination with other lipid-lowering therapies in patients who are statinintolerant, or for whom a statin is contraindicated.
- • On December 1, 2017, Amgen announced that following priority review of its supplemental Biologics License Application, the FDA approved Repatha® (evolocumab) as the first PCSK9 inhibitor to prevent heart attacks, strokes and coronary revascularizations in adults with established cardiovascular disease. In the Repatha® cardiovascular outcomes study (FOURIER), Repatha® reduced the risk of heart attack by 27 percent, the risk of stroke by 21 percent and the risk of coronary revascularization by 22 percent. The FDA also approved Repatha to be used as an adjunct to diet, alone or in combination with other lipid-lowering therapies, such as statins, for the treatment of adults with primary hyperlipidemia to reduce low density lipoprotein cholesterol (LDL-C).
- • On July 27, 2017, Amgen announced that the FDA has granted priority review for Amgen's supplemental Biologics License Application (sBLA) for Repatha® (evolocumab). If approved by the FDA, the U.S. Prescribing Information for Repatha will be updated to include risk reduction of major cardiovascular events based on data from the large cardiovascular outcomes study (FOURIER). The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of Dec. 2, 2017.
- A second application seeking to expand the lipid-lowering indication to include additional patient populations studied was also accepted by the FDA.
- The 27,564-patient Repatha cardiovascular outcomes study (FOURIER) demonstrated that adding Repatha® to optimized statin therapy resulted in a statistically significant 20 percent reduction in hard major adverse cardiovascular events (MACE) represented in the composite (secondary) endpoint of time to first heart attack, stroke or cardiovascular death. The study found a statistically significant 15 percent reduction in the risk of the extended MACE composite (primary) 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 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. For the secondary composite endpoint, an exploratory analysis showed a reduction in risk of 16 percent in the first year and 25 percent beyond the first year.
- Patients on Repatha® experienced a reduction in the risk of heart attack (27 percent), stroke (21 percent) and coronary revascularization (22 percent). Consistent with recent trials of more intensive LDL lowering, there was no observed effect on cardiovascular mortality. Similarly, there was no observed effect on hospitalization for unstable angina.
- • On June 5, 2017, Amgen announced the submission of a supplemental Biologics License Application (sBLA) to the FDA and a variation to the marketing authorization to the European Medicines Agency (EMA) for Repatha® (evolocumab), a PCSK9 inhibitor. The regulatory submissions are based on the 27,564-patient Repatha® cardiovascular outcomes study (FOURIER), which showed that maximally reducing low-density lipoprotein cholesterol (LDL-C) levels with Repatha, beyond what is possible with the current best therapy alone, leads to a further reduction in major cardiovascular events, including heart attacks, strokes and coronary revascularizations.
Submission of marketing authorization application USA : 2017-06-05
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2017-12-01
Favourable opinion UE: 2018-03-22
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: