Pooled Data from Four Phase 2 Studies Demonstrated Consistent Reductions in LDL Cholesterol of Up to 59 Percent
THOUSAND OAKS, Calif., Aug. 31, 2013 /PRNewswire/ -- Amgen (NASDAQ: AMGN) today announced treatment with AMG 145 resulted in significant reductions in low-density lipoprotein cholesterol (LDL-C), or "bad" cholesterol, of up to 59 percent in an efficacy analysis of pooled data from four 12-week Phase 2 studies evaluating AMG 145 in patient populations with high cholesterol. AMG 145 is an investigational human monoclonal antibody that inhibits PCSK9, a protein that reduces the liver's ability to remove LDL-C from the blood. Amgen presented the data at the ESC Congress 2013, organized by the European Society of Cardiology, in Amsterdam.
Elevated LDL-C is recognized as a major risk factor for cardiovascular (CV) disease.1,2 Despite the availability of various treatments to lower LDL-C, it is estimated that in two-thirds of treated, high-risk patients, LDL-C is not well-controlled.3,4
"Millions of people around the world are unable to control their LDL cholesterol with currently available treatment options," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "The data that we have accumulated in our Phase 2 clinical program is evidence that AMG 145 has the potential to help patients reach their cholesterol goals. We are conducting a large and comprehensive Phase 3 clinical program evaluating AMG 145 in multiple patient populations and utilizing two dosing schedules, with the hopes of advancing care and improving the lives of patients with uncontrolled high LDL cholesterol."
Results from the efficacy analysis showed mean reductions in LDL-C from baseline to week 12, as measured by preparative ultracentrifugation, ranged from 40 to 59 percent across AMG 145 doses in comparison to 0.1 to 0.5 percent for placebo (p=0.001). AMG 145 treatment was also associated with improvements in other lipid parameters, including high-density lipoprotein cholesterol (HDL-C), triglycerides, apolipoprotein B, lipoprotein(a) and apolipoprotein A1, within each targeted dose frequency of AMG 145.
In the safety analysis, adverse events (AEs) were observed more frequently with AMG 145 than placebo (57 percent vs. 49 percent) with the most frequent AEs being nasopharyngitis (8.3 percent vs. 7.5 percent) and upper respiratory tract infection (4.1 percent vs. 3.3 percent). Serious AEs were 2.0 percent with AMG 145 and 1.2 percent with placebo. The rates of injection-site reactions were similar between patients treated with AMG 145 and those treated with placebo (4.1 percent vs. 3.3 percent) while muscle-related AEs and anti-drug binding antibodies were 6.0 percent vs. 3.9 percent and 0.1 percent vs. 0.3 percent, respectively.
About the Pooled Analyses
The pre-specified, pooled analyses of data were from four Phase 2, placebo-controlled, randomized trials of AMG 145 in various patient populations with hyperlipidemia. In each trial, treatment duration was 12 weeks and the primary endpoint was percentage change in LDL-C from baseline, as measured by ultracentrifugation. Patients enrolled in the trials received various doses of AMG 145 subcutaneously every two weeks or monthly. Three of the four trials permitted stable background statin therapy. The trials included:
– MENDEL (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Patients Currently Not Receiving Drug Therapy for Easing Lipid Levels) evaluated the efficacy, safety and tolerability of AMG 145 administered subcutaneously every two weeks and every four weeks in hyperlipidemic patients (LDL-C ³ 100 mg/dL and < 190 mg/dL) 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) evaluated the efficacy, safety and tolerability of AMG 145 administered subcutaneously every two weeks and every four weeks in hyperlipidemic patients at risk for CV disease (LDL-C > 85 mg/dL) when added to a stable dose of statin, with or without ezetimibe.
– RUTHERFORD (RedUction of LDL-C With PCSK9 InhibiTion in HEteRozygous Familial HyperchOlesteRolemia Disorder Study) evaluated AMG 145 administered subcutaneously every month, in heterozygous familial hypercholesterolemic patients with an LDL-C >100 mg/dL who were on a stable dose of statin, with or without ezetimibe.
– GAUSS (Goal Achievement After Utilizing an anti-PCSK9 Antibody in Statin Intolerant Subjects) evaluated the efficacy, safety and tolerability of AMG 145 dosed subcutaneously every month, in hyperlipidemic patients who could not tolerate effective statin doses due to muscle-related side effects.
About AMG 145
AMG 145 is a 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.5 AMG 145, 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.6
About the AMG 145 Clinical Trial Program
PROFICIO, which stands for the Program to Reduce LDL-C and Cardiovascular Outcomes Following Inhibition of PCSK9 In Different POpulations, is the large and comprehensive clinical trial program evaluating AMG 145.
The Phase 3 clinical trial program for AMG 145 builds upon the successful Phase 2 studies and includes 12 trials, with a combined planned enrollment of more than 27,000 patients. The Phase 3 studies will evaluate AMG 145 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 AMG 145 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 AMG 145 compared to placebo reduces recurrent cardiovascular events in approximately 22,500 patients with cardiovascular disease.
Additional information about clinical trials of AMG 145 can be found at www.clinicaltrials.gov.
About Amgen
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 understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its biologics manufacturing expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be the world's largest independent biotechnology company, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.
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1. American Heart Association (2012). Why cholesterol matters. http://www.heart.org/HEARTORG/Conditions/Cholesterol/WhyCholesterolMatters/Why-Cholesterol-Matters_UCM_001212_Article.jsp. Accessed August 2013
2. World Health Organization. Global status report on noncommunicable diseases 2010. Geneva, 2011.
3. Roger V et al. Heart disease and stroke statistics – 2011 update: A report from the American Heart Association. Circulation.2011;123:e18-e209.
4. Durrington P. Dyslipidaemia.The Lancet.2003;362:717–311.
5. Abifadel M et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 2003;34:154- 156.
6. Amgen data on file, Investigator Brochure.
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