Canakinumab for secondary prevention of atherosclerotic disease

ABSTRACT

Introduction: The widespread prevalence of cardiovascular disease (CVD) and its impact on morbidity and mortality requires effective secondary prevention measures. For years, inflammation has been advocated as a key mediator of atherosclerosis and its associated complications. Drugs for secondary prevention of CVD events include interventions aimed at risk factors control and antithrombotic management, but there is no drug currently recommended that specifically targets inflammation. Recently, the inflammatory hypothesis of atherosclerosis has been confirmed by a randomized clinical trial of canakinumab, a monoclonal antibody that blocks an inflammatory pathway mediated by interleukin-1β.

Areas covered: This article reviews the pharmacology of canakinumab, its current clinical development status and upcoming regulatory perspectives.

Expert opinion: In the CANTOS trial, canakinumab 150 mg met the pre-specified criteria of statistical significance, showing a reduction in combined cardiovascular events, myocardial infarction, re-hospitalization due to urgent revascularization and any coronary revascularization, but no impact on all-cause or cardiovascular death. There were more death attributed to sepsis or infection with canakinumab than placebo, but fewer reports of arthritis, gout, osteaoarthritis and cancer-related death. Because interleukin-1β is only one of the potential pro-inflammatory pathways that may serve as a target for atherothrombotic protection, other anti-inflammatory drugs may be the object of future investigations. If approved, the initial penetration of canakinumab will face hurdles in view of cost issues, but costs are likely to decrease if the drug loses its present status of orphan drug with the new indication.

KEYWORDS:

• Canakinumab
• interleukin-1β
• inflammation

Declaration of interest

D Capodanno has received consulting fees or honoraria from Daiichi-Sankyo, The Medicines Company, AstraZeneca, Sanofi, and Bayer. D Angiolillo has received payments as an individual for a consulting fee or honorarium from Amgen, AstraZeneca, Bayer, Chiesi, Daiichi-Sankyo, Eli Lilly, Janssen, Merck, PLx Pharma, Pfizer, and Sanofi; participation in review activities from CeloNova and St. Jude Medical; and has received institutional payments for grants from Amgen, AstraZeneca, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Matsutani Chemical Industry Co., Merck, Novartis, and Renal Guard Solutions. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

One of the three reviewers declares that serve on a scientific advisory board for Novartis, which makes canukinumab. No other reviewers declare any potential conflict of interest.

Additional information

Funding

No funding to declare.