Studies Showed Sustained Reduction in LDL-C With no new Safety Findings
The Combined Studies Evaluated Safety and Tolerability of Repatha in More Than 6,600 Patients for Over Five Years After Completing the Phase 3 FOURIER Trial
Repatha is the Longest Studied PCSK9i
THOUSAND OAKS, Calif., April 27, 2022 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced top-line results from two Repatha® (evolocumab) open label extension (OLE) studies to the Phase 3 FOURIER cardiovascular outcomes trial. The studies were designed to assess the long-term safety and tolerability of Repatha over five years in adults with clinically evident atherosclerotic cardiovascular disease.
The FOURIER-OLE (Further cardiovascular OUtcomes Research with PCSK9 Inhibition in Subjects with Elevated – Risk-Open Label Extension) studies were composed of study 20130295 (NCT02867813) with 5,035 patients enrolled in Eastern Europe and the United States and study 20160250 (NCT03080935) with 1,600 patients enrolled in Western Europe. Both studies showed that Repatha, administered at 140 mg every two weeks or 420 mg monthly, was safe and well-tolerated. In the OLE studies, patients received Repatha for approximately 5 years, with some patients receiving Repatha for up to 8 1/2 years in aggregate across the FOURIER and OLE studies. No new long-term safety findings were observed.
In addition, medically significant and sustained reduction in low-density lipoprotein cholesterol (LDL-C) levels were observed, with more than 85 percent of patients achieving an LDL-C level of <40 mg/dL during the OLE period.
"The combined results from these studies reinforce the well-established safety profile of Repatha with long-term use in lowering LDL-C," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "As the PCSK9i leader, with more than one million patients worldwide who have received Repatha, we are extremely encouraged by the sustained benefit of this effective medicine for patients with cardiovascular disease who still struggle to get their LDL-C level below recommended goals."
Other study measures included exploratory analyses of non-high-density lipoprotein cholesterol, apolipoprotein B, total cholesterol, Lipoprotein(a), triglycerides, high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and apolipoprotein A-1 levels, as well as cardiovascular events of interest.
Detailed study results will be shared with regulatory authorities and submitted for presentation at an upcoming medical congress later this year. Prolonged LDL-C reduction with Repatha is also being studied in the ongoing VESALIUS-CV (NCT03872401) outcomes trial.
Repatha® Cardiovascular Open-Label Extension (FOURIER-OLE) Study Design
FOURIER (20110118) was a randomized placebo-controlled study of evolocumab, in patients with clinically evident atherosclerotic CVD on stable effective statin therapy. FOURIER-OLE (Further cardiovascular OUtcomes Research with PCSK9 Inhibition in Subjects with Elevated – Risk-Open Label Extension) were multicenter, open-label extension (OLE) studies designed to assess the extended long-term safety of evolocumab in subjects who completed the FOURIER study (20110118). The FOURIER-OLE is composed of studies 20130295 and 20160250, which enrolled 5,035 and 1,600 subjects who completed FOURIER study (20110118) to receive open-label evolocumab and were followed up for a median of 5 and 4.6 years, respectively.
FOURIER is part of Amgen's PROFICIO (Program to Reduce LDL-C and cardiovascular Outcomes Following Inhibition of PCSK9 In different pOpulations) program of clinical studies investigating the impact of Repatha® on LDL-C and CVD across multiple populations at high CV risk, including those managed by statins, statin-intolerant patients, those with genetic disorders and patients with atherosclerosis. To date, the PROFICIO program consists of 36 trials including more than 38,000 patients worldwide.
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About Repatha® (evolocumab)
Repatha® 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 75 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.
Repatha® is indicated:
- In adults with established cardiovascular disease to reduce the risk of myocardial infarction, stroke, and coronary revascularization
- As an adjunct to diet, alone or in combination with other low-density lipoprotein cholesterol (LDLC)-lowering therapies, in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce LDL-C
- As an adjunct to diet and other LDL-C-lowering therapies in pediatric patients aged 10 years and older with HeFH, to reduce LDL-C
- As an adjunct to other LDL-C-lowering therapies in adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH), to reduce LDL-C
The safety and effectiveness of Repatha® have not been established in pediatric patients with HeFH or HoFH who are younger than 10 years old or in pediatric patients with other types of hyperlipidemia.
IMPORTANT SAFETY INFORMATION
Contraindication: Repatha® is contraindicated in patients with a history of a serious hypersensitivity reaction to evolocumab or any of the excipients in Repatha®. Serious hypersensitivity reactions including angioedema have occurred in patients treated with Repatha®.
Hypersensitivity Reactions: Hypersensitivity reactions, including angioedema, have been reported in patients treated with Repatha®. If signs or symptoms of serious hypersensitivity reactions occur, discontinue treatment with Repatha®, treat according to the standard of care, and monitor until signs and symptoms resolve.
Adverse Reactions in Adults with Primary Hyperlipidemia: The most common adverse reactions (>5% of patients treated with Repatha® and more frequently than placebo) were: nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions.
From a pool of the 52-week trial and seven 12-week trials: Local injection site reactions occurred in 3.2% and 3.0% of Repatha®-treated and placebo-treated patients, respectively. The most common injection site reactions were erythema, pain, and bruising. Hypersensitivity reactions occurred in 5.1% and 4.7% of Repatha®-treated and placebo-treated patients, respectively. The most common hypersensitivity reactions were rash (1.0% versus 0.5% for Repatha® and placebo, respectively), eczema (0.4% versus 0.2%), erythema (0.4% versus 0.2%), and urticaria (0.4% versus 0.1%).
Adverse Reactions in the Cardiovascular Outcomes Trial: The most common adverse reactions (>5% of patients treated with Repatha® and more frequently than placebo) were: diabetes mellitus (8.8% Repatha®, 8.2% placebo), nasopharyngitis (7.8% Repatha®, 7.4% placebo), and upper respiratory tract infection (5.1% Repatha®, 4.8% placebo).
Among the 16,676 patients without diabetes mellitus at baseline, the incidence of new-onset diabetes mellitus during the trial was 8.1% in patients treated with Repatha® compared with 7.7% in patients that received placebo.
Adverse Reactions in Pediatric Patients with HeFH: The most common adverse reactions (>5% of patients treated with Repatha® and more frequently than placebo) were: nasopharyngitis, headache, oropharyngeal pain, influenza, and upper respiratory tract infection.
Adverse Reactions in Adults and Pediatric Patients with HoFH: In a 12-week study in 49 patients, the adverse reactions that occurred in at least two patients treated with Repatha® and more frequently than placebo were: upper respiratory tract infection, influenza, gastroenteritis, and nasopharyngitis. In an open-label extension study in 106 patients, including 14 pediatric patients, no new adverse reactions were observed.
Immunogenicity: Repatha® is a human monoclonal antibody. As with all therapeutic proteins, there is potential for immunogenicity with Repatha®.Please contact Amgen Medinfo at 800-77-AMGEN (800-772-6436) or 844-REPATHA (844-737-2842) regarding Repatha® availability or find more information, including full Prescribing Information, at www.amgen.com and www.Repatha.com.
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