CSL Behring Advances to Phase III Cardiovascular Outcomes Trial for CSL112, its Novel Apolipoprotein A-I (Human) Infusion Therapy


Study to evaluate CSL112 for the reduction of early, recurrent cardiovascular events in heart attack survivors


KING OF PRUSSIA, Pa., Dec. 4, 2017 /PRNewswire/ -- Global biotherapeutics leader CSL Behring today announced that it will proceed with a global Phase 3 cardiovascular morbidity and mortality trial for CSL112, the company's novel apolipoprotein A-I (apoA-I) infusion therapy. The study, ApoA-I Event reducinG in Ischemic Syndromes II (AEGIS-II), will enroll more than 17,000 patients from approximately 1,000 sites around the world to evaluate whether CSL112 reduces cardiovascular events in high-risk patients during the critical 90 days after a heart attack. The decision was announced during CSL's annual R&D Investor Briefing.

Cardiovascular disease (CVD) is the leading cause of death globally. Every year in the US, an estimated 800,000 people will suffer an acute myocardial infarction (MI), or heart attack, and nearly one in five survivors will experience a recurrent cardiovascular event (non-fatal MI, stroke, cardiovascular death) within one year. The majority of these recurrent events happen within the first 90 days and are associated with a high rate of morbidity and mortality. In addition, recurrent events are associated with increased economic and healthcare burden.

"Despite recent advances in cardiovascular care, we still have an unacceptable rate of early recurrent cardiovascular events occurring in high-risk patients following an acute MI," said C. Michael Gibson, M.D., Ph.D., Professor of Medicine at Harvard Medical School and co-lead investigator of the AEGIS-II study. "We are optimistic that CSL112 will offer a novel, rapid approach to reduce these events during the 90-day period when heart attack survivors are most vulnerable."

Early recurrent cardiovascular events are commonly caused by the rupture or erosion of cholesterol-rich plaque in the arteries. CSL112 may offer a novel approach through the rapid enhancement of cholesterol efflux capacity, a process by which cholesterol is removed from plaque and transported to the liver for elimination from the body.

"The decision to proceed to Phase 3 of the clinical program for CSL112 reflects our promise to patients and deep commitment to innovation, along with our heritage of delivering plasma-derived therapies," said Andrew Cuthbertson, Chief Scientific Officer and R&D Director for CSL Limited. "We believe CSL112 has the potential to change the current treatment paradigm for heart attack survivors and improve global health outcomes for the millions of people at risk for early recurrent cardiovascular events."

Positive results from AEGIS-I were presented at the American Heart Association Scientific Sessions in New Orleans, LA, in November 2016 and published online in Circulation. The multicenter, randomized, double-blind, placebo-controlled, dose-ranging, Phase 2b safety and proof of mechanism trial enrolled 1,258 acute MI patients. Patients were stratified by renal function and randomized to receive four weekly infusions of either CSL112 2g/dose, CSL112 6g/dose or placebo.

The study met its co-primary safety endpoints, showing that CSL112 does not cause significant changes in liver or kidney function and demonstrating that it is well tolerated when administered in the acute MI setting. The study also provided confirmation of CSL112's unique mechanism of action, cholesterol efflux enhancement, as demonstrated by an immediate, up to four-fold increase compared to baseline in cholesterol efflux capacity.

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 MACE (Major Adverse Cardiac Event), defined as cardiovascular death, myocardial infarction, and stroke in acute coronary syndrome (ACS) patients who are receiving evidence-based medical therapy, diagnosed with either ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI), including those managed with percutaneous coronary intervention (PCI) or medically managed. AEGIS-II is expected to complete over a four-year period, with patient enrollment beginning in early 2018.

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.

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 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.

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.

CSL Behring operates one of the world's largest plasma collection networks, CSL Plasma. The parent company, CSL Limited (ASX: CSL; USOTC: CSLLY), headquartered in Melbourne, Australia, employs nearly 20,000 people, and delivers its life-saving therapies to people in more than 60 countries. For more information visit www.cslbehring.com and follow us on www.Twitter.com/CSLBehring.

Natalie de Vane
CSL Behring
Mobile: 610-999-8756
Office: 610-878-4468

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Company Codes: Australia:CSL, OTC-PINK:CSLLY, OTC-BB:CSLLY

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