Topline Findings
- FDA Expands Repatha Indication: Repatha is now approved for adults at increased risk for major adverse cardiovascular events (MACE) due to uncontrolled low-density lipoprotein cholesterol (LDL-C), removing the prior requirement of diagnosed cardiovascular disease.
- Multiple Label Updates Over Time: Since its 2015 approval, Repatha has gained expanded indications, including use in homozygous familial hypercholesterolemia, pediatric patients aged 10 years and older, and prevention of heart attacks, strokes, and coronary revascularizations.
- High Real-World MACE Risk: A 2020 study of over 1.3 million patients found that individuals with established atherosclerotic disease or multiple risk factors face significant MACE risk, reinforcing the need for additional LDL-C–lowering therapies.
The FDA has updated the label for Amgen’s Repatha (evolocumab) to include adults at increased risk for major adverse cardiovascular events (MACE) linked to uncontrolled low-density lipoprotein cholesterol (LDL-C). The expanded indication removes the prior restriction that patients must already have diagnosed cardiovascular disease (CVD), broadening access to individuals considered to have an elevated risk.1
What Milestones have Shaped Repatha’s Label Expansion Over the Years?
"Far too many adults at risk of cardiovascular disease are not achieving their LDL-C goals, despite it being one of the most modifiable risk factors for a heart attack or stroke," said Murdo Gordon, EVP, global commercial operations, Amgen, in a press release.
The FDA also extended the approval of Repatha to include it as a standalone therapy for patients with homozygous familial hypercholesterolemia (HoFH), a rare inherited condition that causes dangerously high cholesterol levels. The agency further underscored that Repatha should be prescribed in combination with diet and lifestyle measures to manage cholesterol effectively.1
RepathaInitial Approval and Expanded Indications
Repatha was first approved in 2015 to treat adults with HoFH or established CVD whose LDL cholesterol could not be adequately controlled with statins alone.2 Prior to this most recent label update, Repatha was granted the following indications by the FDA:
- In December 2017, Repatha became the first PCSK9 inhibitor indicated to prevent heart attacks, strokes, and coronary revascularizations in adults with established CVD. Approval was based on the Phase III FOURIER trial, which showed Repatha significantly reduced MACE when added to statin therapy. The FDA also expanded Repatha’s use to include treatment of primary hyperlipidemia in adults, either alone or with other lipid-lowering therapies, to further reduce LDL-C.4
- In September 2021, Repatha was approve by the FDA as an adjunct to diet and other LDL-C–lowering therapies for pediatric patients aged 10 years and older with HoFH. The approval was supported by the Phase IIIb HAUSER-RCT trial, which demonstrated a mean 38% LDL-C reduction compared to placebo, along with improvements in non-HDL cholesterol, total cholesterol, and ApoB.5
Real-World Risk Highlights Need for Expanded Access to Repatha
The decision to expand Repatha’s label reflects the persistent risk of cardiovascular events among at-risk patients. According to a 2020 study published in the National Center for Biotechnology Information, patients with established atherosclerotic CVD or multiple risk factors remain at notable risk for MACE.
Drawing on real-world data from more than 1.3 million patients aged 45 years and older, the study reported a 1.4% incidence of MACE within one year, rising to 6.9% at four years. The analysis also showed that risk climbed sharply with the number of vascular beds affected, with patients facing more than triple the risk if disease was present in the coronary, cerebrovascular, and peripheral arteries simultaneously.6
"This label update highlights the real-world need for additional treatment options for at-risk patients,” continued Gordon, in the press release. “Repatha is an effective therapy for reducing LDL-C, particularly in patients whose disease remains uncontrolled with statins or who cannot tolerate them."
References
- REPATHA® NOW INDICATED FOR ADULTS AT INCREASED RISK FOR MAJOR ADVERSE CARDIOVASCULAR EVENTS DUE TO UNCONTROLLED LDL-C. PR Newswire. August 25, 2025. Accessed August 25, 2025. https://prnmedia.prnewswire.com/news-releases/repatha-now-indicated-for-adults-at-increased-risk-for-major-adverse-cardiovascular-events-due-to-uncontrolled-ldl-c-302537326.html
- FDA Approves Repatha. Drugs.com. August 27, 2025. Accessed August 25, 2025. https://www.drugs.com/newdrugs/fda-approves-repatha-evolocumab-certain-patients-cholesterol-4251.html
- FDA Approves Repatha Pushtronex. Drugs.com. July 16, 2025. Accessed August 25, 2025. https://www.drugs.com/newdrugs/fda-approves-repatha-evolocumab-pushtronex-first-only-single-monthly-pcsk9-inhibitor-4416.html
- FDA Approves Amgen's Repatha (evolocumab) to Prevent Heart Attack and Stroke. Drugs.com. December 1, 2017. Accessed August 25, 2025. https://www.drugs.com/newdrugs/fda-approves-amgen-s-repatha-evolocumab-prevent-heart-attack-stroke-4655.html
- FDA Approves Repatha (evolocumab) In Pediatric Patients Age 10 And Older With Heterozygous Familial Hypercholesterolemia. Drugs.com. September 24, 2021. Accessed August 25, 2025. https://www.drugs.com/newdrugs/fda-approves-repatha-evolocumab-pediatric-patients-age-10-older-heterozygous-familial-5668.html
- Incidence and Predictors of Major Adverse Cardiovascular Events in Patients With Established Atherosclerotic Disease or Multiple Risk Factors. PubMed. Accessed August 25, 2025. https://pubmed.ncbi.nlm.nih.gov/31937196/
