Amgen announces evolocumab (AMG 145) results from first 52-week study of a PCSK9 inhibitor to reduce LDL cholesterol

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.²Elevated 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 percent vs. 5.2 percent), arthralgia (6.9 percent vs. 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 52 weeks.

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 general public.

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 event.

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 familial hypercholesterolemia.
• 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 2 studies.

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 www.clinicaltrials.gov.

References

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. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6004a5.htm?s_cid=mm6004a5_w. Accessed November 2013
3. American Heart Association (2012). Why cholesterol matters. http://www.heart.org/HEARTORG/Conditions/Cholesterol/WhyCholesterolMatters/Why-Cholesterol-Matters_UCM_001212_Article.jsp. Accessed November 2013.
4. World Health Organization. Global status report on noncommunicable diseases 2010. Geneva, 2011.
5. John Hopkins Medicine. Cardiovascular Disease Statistics. http://www.hopkinsmedicine.org/healthlibrary/conditions/cardiovascular_diseases/cardiovascular_disease_statistics_85,P00243/. Accessed November 2013.
6. Abifadel M, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 2003;34:154-156.