Canakinumab Drug Phase III Study Reducing Heart Attacks

Canakinumab Drug Phase III Study Reducing Heart Attacks

Novartis Phase III study shows ACZ885 (canakinumab) reduces cardiovascular risk in people who survived a heart attack

  • Phase III CANTOS study met the primary endpoint, a composite of heart attack, stroke and cardiovascular death, showing that ACZ885 (canakinumab) in combination with standard of care therapy reduces cardiovascular risk in people with a prior heart attack and inflammatory atherosclerosis
  • Despite current treatments about 40% of heart attack survivors remain at increased risk of  recurrent heart attack, stroke or cardiovascular death because of high-risk inflammatory atherosclerosis[1]; 25% experience another event within five years[2]

 

Basel, June 22, 2017 – Novartis today announced topline results from the global Phase III CANTOS study investigating the efficacy, safety and tolerability of ACZ885 (canakinumab) in combination with standard of care in people with a prior heart attack and inflammatory atherosclerosis. With more than 10,000 patients enrolled in the study over the last six years, CANTOS is one of the largest and longest-running clinical trials in Novartis’ history.

The CANTOS study met the primary endpoint, demonstrating that when used in combination with standard of care ACZ885 reduces the risk of major adverse cardiovascular events (MACE), a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke, in patients with a prior heart attack and inflammatory atherosclerosis. The full data from the study will be submitted for presentation at a medical congress and for peer reviewed publication later this year.

“Despite current treatment, about 25 percent of heart attack survivors will have another cardiovascular event within five years, making the outcome of the CANTOS study a promising new development for patients,” said Vas Narasimhan, Global Head, Drug Development and Chief Medical Officer, Novartis. “ACZ885 is the first and only investigational agent which has shown that selectively targeting inflammation reduces cardiovascular risk. Our priority now is to thoroughly analyze these important data and discuss them with regulatory agencies.”

Heart attack occurs in about 580,000 people every year in EU5 and 750,000 people in the United States alone[3],[4]. In 2015 there were an estimated 7.29 million heart attacks globally[5]. Despite standard treatment, people with a prior heart attack live with a higher ongoing risk of having another event or dying, and it has been shown that in about four in 10 people, this risk is directly related to increased inflammation associated with atherosclerosis[1]. The recurrent MACE in patients with inflammatory atherosclerosis are associated with increased morbidity, mortality and reduced quality of life and currently represent a major economic burden on patients and healthcare systems around the world.

About CANTOS
The Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) (NCT01327846) is a randomized, double-blind, placebo-controlled, event-driven Phase III study designed to evaluate the efficacy, safety and tolerability of quarterly subcutaneous injections of ACZ885 (also known as canakinumab) in combination with standard of care in the prevention of recurrent cardiovascular (CV) events among 10,061 people with a prior myocardial infarction (MI) and with a high-sensitivity C-reactive protein (hsCRP) level of >=2mg/L. The study evaluated three different doses of ACZ885 vs placebo. The primary endpoint of the study was time to first occurrence of major adverse CV event (MACE), a composite of CV death, non-fatal MI, and non-fatal stroke. Secondary endpoints included time to first occurrence of the composite CV endpoint consisting of CV death, non-fatal MI, non-fatal stroke and hospitalization for unstable angina requiring unplanned revascularization; time to new onset type 2 diabetes among people with pre-diabetes at randomization; time to occurrence of non-fatal MI, non-fatal stroke or all-cause mortality; and time to all-cause mortality. The median follow-up time was 3.8 years. The study ran for approximately six years.

About heart attack and inflammatory atherosclerosis
Heart attack occurs in about 580,000 people every year in EU5 and 750,000 people in the United States alone[3],[4]. In 2015 there were an estimated 7.29 million heart attacks globally[5]. Despite standard treatment, patients who have had a prior heart attack live with a higher ongoing risk of secondary major adverse cardiovascular events (MACE), a composite of cardiovascular (CV) death, non-fatal MI, and non-fatal stroke. It has been shown that in about four in 10 people, this risk is directly related to the increased inflammation associated with inflammatory atherosclerosis as measured by a high-sensitivity C-reactive protein (hsCRP) biomarker level of >= 2mg/L[1]. The recurrent MACE in people with inflammatory atherosclerosis are associated with increased morbidity, mortality and reduced quality of life and currently represent a major economic burden on patients and healthcare systems around the world.

About ACZ885
ACZ885 (canakinumab) is a selective, high-affinity, fully human monoclonal antibody that inhibits IL-1ß, a key cytokine in the inflammatory pathway known to drive the continued progression of inflammatory atherosclerosis[6]-[10]. ACZ885 works by blocking the action of IL-1ß for a sustained period of time, therefore inhibiting inflammation that is caused by its over-production[11],[12]. ACZ885 is the first and only agent which has shown that selectively targeting inflammation significantly reduces cardiovascular risk in patients who have had a prior heart attack and have an increased cardiovascular inflammatory burden.

 


 

References
[1] Ridker P. How Common Is Residual Inflammatory Risk? Circ Res. 2017;120:617-619
[2] Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation. 2017;135:e146-e603
[3] EU5 MI trend. Based on Eurostat discharge data. Novartis data on file.
[4] Mozaffarian D, et al. Heart Disease and Stroke Statistics – 2016 Update: A Report From the American Heart Association. Circulation. 2017; 135(23):e1-324.
[5] Roth G, et al. Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015. JACC. Available online May 17, 2017.
[6] Fearon WF, Fearon DT. Inflammation and cardiovascular disease: role of the interleukin-1 receptor antagonist. Circulation. 2008;117:2577-2579.
[7] Duewell P, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature. 2010;464(7293):1357-61.
[8] Rajamaki K, et al. Cholesterol Crystals Activate the NLRP3 Inflammasome in Human Macrophages: A Novel Link between Cholesterol Metabolism and Inflammation. PLoS One. 2010; 5(7):e11765.
[9] Ridker PM, Luscher TF. Anti-inflammatory therapies for cardiovascular disease. Eur Heart J. 2014; 35(27):1782-91.
[10] Ridker PM. From C-Reactive Protein to Interleukin-6 to Interleukin-1. Circ Res. 2016; 118:145-156.
[11] Ridker PM, et al. Effects of Interleukin-1ß Inhibition with Canakinumab on Hemoglobin A1c, C-Reactive Protein, Interleukin-6 and Fibrinogen. Circulation. 2012; 126(23):2739-48.
[12] Ridker PM, et al. Interleukin-1ß inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J. 2011; 162(4):597-605.


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