CSL Behring Announces First Patient Enrollment in Phase 3 Clinical Trial of CSL112 to Assess Reduction of Early Recurrent Cardiovascular Events in Heart Attack Survivors

 CSL Behring, a global biotherapeutics leader, today announced the initiation of the AEGIS-II (ApoA-I Event reducinG in Ischemic Syndromes II) clinical trial and the first patient enrollment. The clinical trial will evaluate the efficacy and safety of CSL112 for the reduction of early recurrent cardiovascular events following an acute myocardial infarction (MI). CSL112 is a novel apolipoprotein A-I infusion therapy that has been shown to have an immediate and significant impact on the ability to remove cholesterol from arteries. The AEGIS-II trial will enroll more than 17,000 patients from approximately 1,000 medical centers around the world.

Cardiovascular disease is the leading cause of death globally, with an estimated 800,000 acute MIs occurring each year in the US alone. Patients who survive an acute MI are at high risk of experiencing early recurrent cardiovascular events. The majority of these events occur in the weeks and months following the initial event and are associated with a high rate of morbidity and mortality.

"The AEGIS-II study will tell us if a rapid enhancement of the body's ability to remove cholesterol from the arteries can reduce the rate of early recurrent CV events in heart attack survivors," said C. Michael Gibson, M.D., M.S., Professor of Medicine at Harvard Medical School and Chairman of the AEGIS-II study. "CSL112 is an exciting new approach in cardiovascular medicine that may help protect our patients when they are most vulnerable."

CSL112 is a novel formulation of apoA-I derived from human plasma. Research has shown that CSL112 can produce an immediate and significant enhancement in cholesterol efflux capacity, a measurement of the body's ability to remove excess cholesterol from cells. CSL112 is the only apoA-I therapy to proceed to a large-scale Phase 3 cardiovascular clinical trial.

"The enrollment of the first patient into AEGIS-II is an important milestone in the AEGIS clinical program and the development of CSL112 as a potential innovative approach for preventing early recurrent cardiovascular events in heart attack survivors," said Andrew Cuthbertson, Chief Scientific Officer and R&D Director for CSL Limited. "CSL's research with CSL112 reflects our ongoing commitment to improve the lives of patients through the discovery and development of novel therapies."

MORE ON AEGIS-II 
AEGIS-II is a Phase 3, multicenter, double-blind, randomized, placebo-controlled, parallel-group study designed to evaluate the efficacy and safety of CSL112 on reducing the risk of major adverse cardiovascular events (MACE), defined as heart attack, stroke or cardiovascular death, in patients with acute coronary syndrome (ACS). This includes patients with either ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI), and those managed with percutaneous coronary intervention (PCI) or medically managed. Patients with unstable angina will be excluded from the study. The study will enroll approximately 17,400 patients from 1,000 sites in 40 countries.

Patients will be randomized in a 1:1 ratio and will receive either CSL112 6g or placebo, administered through IV infusion once weekly for four consecutive weeks. The primary endpoint is the first occurrence of MACE from the time of randomization through 90 days. Patients will continue to be followed for a total of 365 days.

AEGIS-II is being conducted under the academic leadership of the PERFUSE Group at Beth Israel Deaconess Medical Center, the Duke Clinical Research Institute, and the Stanford Cardiovascular Institute and is expected to be completed within approximately four years.

ABOUT THE AEGIS CLINICAL STUDY PROGRAM 
Prior to AEGIS-II, results from the Phase 2b AEGIS-I study were presented at the American Heart Association Scientific Sessions 2016 and published in Circulation. A multicenter, randomized, double-blind, placebo-controlled, dose-ranging study, AEGIS-I met its primary safety endpoints, showing CSL112 did not cause significant changes in liver or kidney function and was well tolerated when administered to patients who experienced a heart attack. The study also confirmed CSL112's mechanism of action, cholesterol efflux enhancement, as demonstrated by an immediate, up to four-fold increase compared to baseline in cholesterol efflux capacity.

An additional Phase 2 trial demonstrated renal safety of CSL112 in patients with moderate renal impairment who experienced a heart attack. The data were presented at the American College of Cardiology's 67th Annual Scientific Session and published in the Journal of the American College of Cardiology.

ABOUT CARDIOVASCULAR DISEASE & RECURRENT EVENTS 
An estimated 17.7 million people died from cardiovascular diseases in 2015, which accounted for 31 percent of all global deaths. Of these deaths, an estimated 7.4 million were due to coronary heart disease. The most common cause of coronary heart disease is the build-up of fatty deposits (atherosclerosis) within the inner walls of the arteries that supply blood to the heart. A well-known clinical manifestation of coronary heart disease is acute myocardial infarction (MI). Patients who suffer an MI may also have atherosclerosis in other vascular beds, which can further increase the risk of recurrent events. In the US alone, a heart attack occurs roughly every 40 seconds. Despite optimal care, approximately one in five patients will experience a recurrent cardiovascular event in the year following an acute MI, with approximately 60-70 percent of recurrent events occurring in the first 90 days following the initial event.

ABOUT CSL112 
CSL112, Apolipoprotein A-I (Human), is a novel formulation of plasma-derived apoA-I, the primary functional component of HDL. It is reconstituted to form HDL-like particles suitable for intravenous infusion. Studies have shown that infusion of CSL112 rapidly enhances cholesterol efflux capacity. CSL112 may offer a new approach for rapidly stabilizing atherosclerotic plaque lesions and is being developed for reduction in the risk of early cardiovascular events in acute myocardial infarction patients.

ABOUT CSL BEHRING 
CSL Behring is a global biotherapeutics leader driven by its promise to save lives. Focused on serving patients' needs by using the latest technologies, we develop and deliver innovative therapies that are used to treat coagulation disorders, primary immune deficiencies, hereditary angioedema, inherited respiratory disease and neurological disorders. The company's products are also used in cardiac surgery, organ transplantation, burn treatment and to prevent hemolytic disease of the newborn.

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