Amgen Presents Results Highlighting The Long-Term Safety And Efficacy Of Repatha (Evolocumab) In The Longest Duration Study Of A PCSK9 Inhibitor To Date At AHA Scientific Sessions 2018
Additional Data Analyzing Treatment Patterns in the United States Shows Underutilization of LDL-C Lowering Treatments in At-Risk Patients and Need for Improved Patient Awareness of Treatment Goals
THOUSAND OAKS, Calif.,/ --?Amgen (NASDAQ:AMGN) today announced the final report of the Open-Label Study of Long-TERm Evaluation Against LDL-C (OSLER-1), demonstrating long-term treatment with Repatha? (evolocumab) was associated with robust and consistent reductions in low-density lipoprotein cholesterol (LDL-C), with no increase in overall rates of adverse events over time and no neutralizing antibodies. Additionally, data from the Getting to an ImprOved Understanding of Low-Density Lipoprotein and Dyslipidemia Management (GOULD) Registry reflect a disconnect between physician perception of lipid-lowering therapies (LLTs) and their actual use, and highlight both a need for improved patient awareness of the goals of LLT and a need to address barriers to use of medications like Repatha.
In an effort to help more patients bring down the risk of heart attack and stroke, Amgen recently made Repatha available in the United States (U.S.)?at a 60 percent reduced list price to address concerns over high out-of-pocket costs for patients. The results of all analyses were presented at the American Heart Association's Scientific Sessions 2018 in Chicago.
OSLER-1 is a five-year, open-label study evaluating the safety and efficacy of Repatha in hypercholesterolemia patients, including those with heterozygous familial hypercholesterolemia, on background statin therapy and patients with statin intolerance who were previously enrolled in one of five double-blind Repatha trials (N=1,324).1-6 Patients treated with Repatha achieved a 59 percent reduction in mean LDL-C from baseline during the first year of treatment (n=785). With Repatha, the mean LDL-C reductions at years two, three, four and five were: 56 percent (n=1,071), 57 percent (n=1,001), 56 percent (n=943) and 56 percent (n=803), respectively. Adverse events (AE) were reported in 80 percent, 74 percent, 71 percent, 67 percent, and 65 percent of patients, respectively; serious AEs were reported in seven percent, seven percent, eight percent, seven percent, and seven percent of patients each year (years one through five, respectively).
"Amgen is pleased to present the results of OSLER-1, the longest study of a PCSK9 inhibitor to date, which clearly demonstrate the durable, long-term efficacy and safety of Repatha in reducing LDL-C levels," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "These findings are consistent with those observed in the Repatha cardiovascular outcomes study (FOURIER) and other Phase 3 trials, reinforcing Repatha's role in the treatment of high-risk patients who are unable to achieve sufficient LDL-C reduction through other means."
Analyses of data from GOULD, a multicenter, observational registry of people with atherosclerotic cardiovascular disease (ASCVD) designed to describe LDL-C treatment patterns in the U.S. over time (N= 5,006), demonstrated the underutilization of effective LLTs among patients at high-risk for cardiovascular events, in those with LDL-C levels = 70 mg/dL. A survey of 110 physicians identified a disconnect between physicians' perceptions of LLTs and their actual use, with support for high-intensity statins and PCSK9 inhibition use at 75 percent among physicians and actual observed use of 50 percent and 10 percent, respectively. While many physicians had prescribed a PCSK9 inhibitor, those who had not, cited cost and hassle associated with prior authorization requirements from payers as important reasons for not prescribing.
Furthermore, among patients receiving any LLT, more than 70 percent did not know the main goal of this treatment was prevention of cardiovascular events and nearly half were unaware of their total lipid levels. GOULD data also demonstrated that, regardless of LLT type, a large proportion of patients remain unaware of their ASCVD risk, LDL-C levels, or therapy goals. This highlights an educational gap, which if addressed, may impact shared healthcare decision making and treatment adherence.
"Despite decades of research that has demonstrated the clear connection between lowering LDL-C levels and reducing the risk for cardiovascular events, several challenges, including cost and low awareness of this critical link have negatively impacted the use of PCSK9 inhibitors," said Murdo Gordon, executive vice president Global Commercial Operations at Amgen. "As demonstrated by our recent decision to make Repatha available in the U.S. at a 60 percent reduced list price, Amgen remains steadfast in its commitment to improving affordability for patients and supporting educational initiatives with the goal of advancing the effective management of LDL-C in high-risk patients to reduce cardiovascular risk."
OSLER-1 is part of Amgen's Program to Reduce LDL-C and cardiovascular Outcomes Following Inhibition of PCSK9 In different pOpulations (PROFICIO). PROFICIO is a large and comprehensive scientific research program evaluating Repatha in 32 clinical trials to date, with a combined enrollment of approximately 38,700 patients.7
OSLER-1 Study Design
Open Label Study of Long-TERm Evaluation Against LDL-C 1 (OSLER-1) is an open-label extension study with Repatha, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. The study was conducted across 192 sites in 18 countries.
Patients were eligible for participation in OSLER-1 provided that they did not discontinue treatment due to a treatment-related serious adverse event (SAE) during their qualifying Phase 2 study or require unblinded lipid measurements and/or adjustment of background lipid therapy during the first 12 weeks of OSLER-1. During the first year, patients were randomized 2:1 to Repatha 420 mg monthly in addition to standard of care (SOC) or SOC alone. After year one, all patients continuing in the study received Repatha 420 mg monthly in addition to SOC for the remaining 4 years of the study. Lipid parameters, safety and tolerability were assessed every 12 weeks.
The primary objective of the study is to evaluate the long-term safety and tolerability of Repatha. The secondary objective is to evaluate LDL-C reductions with Repatha over an extended period of time.
GOULD Study Design
Getting to an ImprOved Understanding of Low-Density Lipoprotein and Dyslipidemia Management (GOULD) Registry is a multicenter, observational registry of ASCVD patients, to describe LDL-C treatment patterns in the United States and track them over time. This registry and subsequent analysis sought to better understand the adaptability of lipid management guidelines for patients with ASCVD.
From December 2016 to April 2018, interactive phone surveys with the lead physicians from each of the 120 U.S. centers participating in the registry (1 physician from each center) and patients (N=5,006) were conducted. Patients with ASCVD receiving any pharmacological LLT were eligible for enrollment in 1 of 3 cohorts: 1) currently receiving a PCSK9i antibody, 2) no PCSK9i and LDL-C 70-99 mg/dL, and 3) no PCSK9i and LDL-C = 100 mg/dL. Patients underwent a 1-year retrospective chart review, followed by chart reviews and interviews every 6 months for 2 years.
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.8
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.
Important U.S. Product Information
Repatha is a PCSK9 (proprotein convertase subtilisin kexin type 9) inhibitor antibody indicated:
- to reduce the risk of myocardial infarction, stroke, and coronary revascularization in adults with established cardiovascular disease.
- as an adjunct to diet, alone or in combination with other lipid-lowering therapies (e.g., statins, ezetimibe), for treatment of adults with primary?hyperlipidemia (including heterozygous familial hypercholesterolemia [HeFH]) to reduce low-density lipoprotein cholesterol (LDL-C).
- as an adjunct to diet and other LDL-lowering therapies (e.g., statins, ezetimibe, LDL apheresis) in patients with homozygous familial hypercholesterolemia (HoFH) who require additional lowering of LDLC.
- Koren, M.J., et al. Long-term Low-Density Lipoprotein Cholesterol-Lowering Efficacy, Persistence, and Safety of Evolocumab in Treatment of Hypercholesterolemia: Results Up to 4 Years From the Open-Label OSLER-1 Extension Study. JAMA Cardiol 2, 598-607 (2017).
- Giugliano, R.P., et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study. Lancet 380, 2007-2017 (2012).
- Hirayama, A., et al. Effects of evolocumab (AMG 145), a monoclonal antibody to PCSK9, in hypercholesterolemic, statin-treated Japanese patients at high cardiovascular risk--primary results from the phase 2 YUKAWA study. Circ J 78, 1073-1082 (2014).
- Koren, M.J., et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolaemia (MENDEL): a randomised, double-blind, placebo-controlled, phase 2 study. Lancet 380, 1995-2006 (2012).
- Raal, F., et al. Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD) randomized trial. Circulation 126, 2408-2417 (2012).
- Sullivan, D., et al. Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial. JAMA 308, 2497-2506 (2012).
- Data on File.? (Amgen Thousand Oaks, CA, 2018).
- Repatha Prescribing Information (Amgen, Thousand Oaks, CA 2018).
- WHO, W.H.O. Cardiovascular diseases (CVDs) fact sheet.