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Date: 2019-01-24

Type of information: Granting of a Market Authorisation in China

Product name: Repatha®

Compound: evolocumab

Therapeutic area: Rare diseases - Cardiovascular diseases

Action mechanism:

  • 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)

Disease:

  • 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
  •  prevention of  heart attacks, strokes and coronary revascularizations in adults with established cardiovascular disease.

Latest news:

  • • On January 24, 2019, Amgen announced that the National Medical Products Administration (NMPA) has approved a new indication for Repatha® (evolocumab) as the first PCSK9 inhibitor in China for adults with established atherosclerotic cardiovascular disease (ASCVD) to reduce the risk of myocardial infarction, stroke and coronary revascularization.
  • The approval of the extended label recognizes the positive findings from the 27,564-patient Repatha® cardiovascular outcomes study (FOURIER). Compared to placebo plus statin therapy, patients on Repatha® in combination with statin therapy, experienced a reduction in the risk of heart attack by 27 percent, the risk of stroke by 21 percent and the risk of coronary revascularization by 22 percent, accruing through the median 26 months of the study. Moreover, the results from a FOURIER subanalysis demonstrated consistent efficacy and safety in the reduction of cardiovascular events using Repatha in Asian populations versus those from non-Asian backgrounds. On July 31, 2018 , Repatha was approved by the NMPA as the first PCSK9 inhibitor in China for the treatment of adults and adolescents over 12 years old with homozygous familial hypercholesterolemia (HoFH).
  • • On May 16, 2018, Amgen announced that the European Commission has approved a new indication in the Repatha® label for adults with established atherosclerotic cardiovascular disease (myocardial infarction, stroke or peripheral arterial disease) to reduce cardiovascular risk by lowering low-density lipoprotein cholesterol (LDL-C) levels. With the expanded label now in place, Amgen is working with payers in Europe to remove prescribing barriers and expand access in order to reach patients with established cardiovascular disease who are at risk of another event. The approval by the EC recognizes the positive findings from the Repatha cardiovascular outcomes study (FOURIER), expanding the label to include data on the additional reduction and prevention of heart attacks, strokes and coronary revascularizations on top of maximally tolerated statin therapy. FOURIER 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. 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).
  • • 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.
 

Patents:

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

UE authorization: 2018-05-16

Favourable opinion UE: 2018-03-22

Favourable opinion USA:

Orphan status USA:

Orphan status UE:

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

  • • On October 24, 2018, Amgen announced that it is making Repatha® (evolocumab) available at a reduced list price of $5,850 per year. This 60 percent reduction from the medicine's original list price will improve affordability by lowering patient copays, especially for Medicare patients. Robert A. Bradway , chairman and chief executive officer at Amgen, noted that an estimated 75 percent of Medicare patients prescribed a PCSK9 inhibitor never actually fill their prescriptions, mainly due to high out-of-pocket costs.
 

Is general: Yes