Amgen Announces Evolocumab (AMG 145) Results From First 52-Week Study Of A
PCSK9 Inhibitor To Reduce LDL Cholesterol
Data Presented at American Heart Association Scientific Sessions 2013 and
Simultaneously Published in Circulation
THOUSAND OAKS, Calif., Nov. 19, 2013
THOUSAND OAKS, Calif., Nov. 19, 2013 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today
announced results from the Open Label Study of Long TERm Evaluation Against
LDL-C (OSLER) trial, a long-term controlled 52-week safety and efficacy study,
that showed monthly treatment with evolocumab (AMG 145), an investigational
fully human monoclonal antibody that inhibits PCSK9, a protein that reduces
the liver's ability to remove low-density lipoprotein cholesterol (LDL-C), or
"bad" cholesterol, from the blood^1, was not associated with a major increase
in adverse events (AEs) versus standard of care (SOC) and produced mean LDL-C
reductions of 52 percent in combination with SOC in patients with high
cholesterol. These data from the first 52-week study of a PCSK9 inhibitor were
presented for the first time today in a Clinical Science: Special Reports
session at the American Heart Association (AHA) Scientific Sessions 2013 in
Dallas and simultaneously published in Circulation.
According to the Centers for Disease Control and Prevention, more than 71
million American adults have high LDL-C.^2 Elevated LDL-C is recognized as a
major risk factor for cardiovascular (CV) disease, which is the number one
cause of death worldwide, claiming more lives each year than cancer, chronic
lower respiratory disease and accidents combined.^3-5
"Phase 2 findings from OSLER, the first reported 52-week evaluation of a PCSK9
inhibitor, are encouraging and suggest evolocumab may be a promising option to
treat hyperlipidemia in a range of at-risk patients," said Sean E. Harper,
M.D., executive vice president of Research and Development at Amgen. "We look
forward to Phase 3 results from our PROFICIO clinical program evaluating the
safety and efficacy of two distinctive dosing options of evolocumab in a range
of at-risk patient populations."
OSLER is an ongoing open-label extension study evaluating the long-term safety
and efficacy of evolocumab in patients with high cholesterol. In the first
year, patients were randomized 2:1 to receive evolocumab and SOC or SOC alone.
"Many patients with high cholesterol struggle to adequately reduce their
LDL-C, a significant contributor to cardiovascular disease," said Michael
Koren, M.D., of the Jacksonville Center for Clinical Research. "The results
from the OSLER study are encouraging as evolocumab may offer a potential
treatment option for patients who cannot control their cholesterol levels."
Adverse events occurred in 81.4 percent of patients treated with evolocumab
and SOC and in 73.1 percent of the SOC group. The five most common AEs in the
evolocumab and SOC group compared to the SOC group were nasopharyngitis (12.2
percent vs. 9.8 percent), upper respiratory tract infections (7.7 percent vs.
7.6 percent), influenza (7.1 percentvs. 5.2 percent), arthralgia (6.9
percentvs. 4.3 percent), and back pain (6.5 percent vs. 5.4 percent). Other
AEs that were reported included muscle-related events (9.2 percent vs. 9.8
percent), elevated liver function tests (1.8 percent vs. 1.6 percent), and
elevated creatine kinase (1.0 percent vs. 1.9 percent) for patients treated
with evolocumab and SOC compared to SOC alone, respectively. Serious AEs
occurred in 7.1 percent of patients treated with evolocumab and SOC and 6.3
percent of the SOC group.
In the OSLER clinical trial, subcutaneous monthly treatment with evolocumab in
combination with SOC resulted in a significant LDL-C decrease versus SOC alone
in patients who previously completed one of four 12-week Phase 2 studies of
evolocumab. After 52 weeks of treatment, patients who first received
evolocumab in the OSLER study experienced an average of 52 percent reduction
in LDL-C, as measured by the accepted standard preparative ultracentrifugation
compared to baseline of the Phase 2 parent study. Patients who received one of
six dosing regimens of evolocumab in the parent studies and received
evolocumab and SOC in OSLER had persistent average LDL-C reductions of 50
percent at the end of the parent study vs. 52 percent at 52 weeks.
Improvements in lipoprotein(a) and apolipoprotein B were also sustained up to
Amgen will also host a webcast investor meeting at AHA on Tuesday, Nov. 19,
at 7 p.m. CST. Sean E. Harper, M.D., executive vice president of Research and
Development at Amgen, along with members of Amgen's clinical development team
and clinical investigators, will participate at the investor meeting to
discuss data being presented at AHA.
Live audio of the investor meeting will be simultaneously broadcast over the
Internet and will be available to members of the news media, investors and the
The webcast, as with other selected presentations regarding developments in
Amgen's business given by management at certain investor and medical
conferences, can be found on Amgen's website, www.amgen.com, under Investors.
Information regarding presentation times, webcast availability and webcast
links are noted on Amgen's Investor Relations Events Calendar. The webcast
will be archived and available for replay for at least 90 days after the
OSLER Study Design
OSLER (Open Label Study of Long TERm Evaluation Against LDL-C Trial) is an
open-label extension study to assess the long-term safety and efficacy of
evolocumab. Patients who completed any of the four 12-week Phase 2 studies of
evolocumab were eligible. The Phase 2 studies included:
– MENDEL (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in
Patients Currently Not Receiving Drug Therapy for Easing Lipid Levels) in
patients who were not receiving statin therapy.
– LAPLACE-TIMI 57 (LDL-C Assessment With PCSK9 MonoclonaL Antibody Inhibition
Combined With Statin ThErapy – Thrombolysis In Myocardial Infarction-57) in
patients on statin therapy.
– RUTHERFORD (RedUction of LDL-C With PCSK9 InhibiTion in HEteRozygous
Familial HyperchOlesteRolemia Disorder Study) in patients with heterozygous
– GAUSS (Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin
Intolerant Subjects) in statin-intolerant patients.
A total of 1,104 patients enrolled in the OSLER extension study. Patients were
randomized 2:1 to receive evolocumab subcutaneously at 420 mg monthly with SOC
or SOC alone for one year. The primary objective was to evaluate the safety
and tolerability of evolocumab on a background of SOC. Secondary objectives
were effects on lipid parameters compared to Phase 2 study baseline levels.
About PROFICIO: The Evolocumab Clinical Trial Program
PROFICIO, which stands for the Program to Reduce LDL-C and Cardiovascular
Outcomes Following Inhibition of PCSK9 In Different POpulations, is a large
and comprehensive clinical trial program evaluating evolocumab. Phase 3
clinical trials for evolocumab are currently underway and build upon the Phase
The Phase 3 program includes 13 trials, with a combined planned enrollment of
more than 28,000 patients. The Phase 3 studies will evaluate evolocumab
administered every two weeks and monthly in multiple patient populations,
including in combination with statins in patients with hyperlipidemia
(LAPLACE-2), in patients with hyperlipidemia who cannot tolerate statins
(GAUSS-2), as a stand-alone treatment in patients with hyperlipidemia
(MENDEL-2), and in patients whose elevated cholesterol is caused by genetic
disorders called heterozygous (RUTHERFORD-2) and homozygous (TESLA and
TAUSSIG) familial hypercholesterolemia.
Five studies of evolocumab will provide long-term safety and efficacy data,
including the FOURIER (Further Cardiovascular OUtcomes Research with PCSK9
Inhibition in Subjects with Elevated Risk) study, which will assess whether
treatment with evolocumab compared to placebo reduces recurrent cardiovascular
events in approximately 22,500 patients with cardiovascular disease.
Additional information about clinical trials of evolocumab can be found at
Evolocumab is a fully human monoclonal antibody that inhibits proprotein
convertase subtilisin/kexin type 9 (PCSK9).^1 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.^6 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
Amgen is committed to unlocking the potential of biology for patients
suffering from serious illnesses by discovering, developing, manufacturing and
delivering innovative human therapeutics. This approach begins by using tools
like advanced human genetics to unravel the complexities of disease and
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manufacturing expertise to strive for solutions that improve health outcomes
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of medicines with breakaway potential.
For more information, visit www.amgen.com and follow us on
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1.Amgen Data on File, Investigator Brochure.
2.CDC Morbidity and Mortality Weekly Report. Vital Signs: Prevalence,
Treatment, and Control of High Levels of Low-Density Lipoprotein
Cholesterol --- United States, 1999--2002 and 2005-2008. February 4, 2011.
Accessed November 2013.
3.American Heart Association (2012). Why cholesterol matters.
Accessed November 2013.
4.World Health Organization. Global status report on noncommunicable
diseases 2010. Geneva, 2011.
5.John Hopkins Medicine. Cardiovascular Disease Statistics.
Accessed November 2013.
6.Abifadel M, et al. Mutations in PCSK9 cause autosomal dominant
hypercholesterolemia. Nat Genet 2003;34:154-156.
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