Investigational anti-inflammatory drug meets primary endpoint in global Phase III CANTOS outcome study
In line with the ground-breaking concept of REPROGRAM not only the cholesterol lowering PCSK9 inhibitors seem to be effective. But now, a purely anti-inflammatory cardiovascular trial with the IL-1ß blocker was positive. Thus, both hypotheses seem to be correct, the cholesterol and the inflammation hypotheses of treating cardiovascular disease.
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, has met its primary endpoint. The CANTOS study evaluated treatment with ACZ885 in over 10,000 patients. The median follow-up time was 3.8 years and study ran for approximately six years.
The full data from the study will be submitted for presentation at this summer’s ESC congress and for peer-reviewed publication later this year.
ACZ885 is a selective, high-affinity, fully human monoclonal antibody that inhibits IL-1β, a key cytokine in the inflammatory pathway known to drive the continued progression of inflammatory atherosclerosis. ACZ885 works by blocking the action of IL-1β for a sustained period of time, therefore inhibiting inflammation that is caused by its over- production.
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 in the prevention of recurrent 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 (50 mg, 150 mg and 300 mg) 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. The CANTOS study was powered to detect a 20% relative risk reduction in MACE. The study required a relative risk reduction of 15% or more in MACE to meet its primary objective The median follow-up time was 3.8 years. The study ran for approximately six years.
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.
“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.”
It has been shown that in about four in ten people, the risk of recurrent CV events after MI is directly related to increased inflammation associated with atherosclerosis. 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.
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