Novartis' Canakinumab Meets Endpoint in Phase III CANTOS Trial

​Swiss multinational pharmaceutical company Novartis has announced that canakinumab (ACZ885), a monoclonal antibody for the treatment of cardiovascular risk, has met the primary endpoint of the phase III CANTOS trial.

In the trial, canakinumab was shown to reduce cardiovascular risk in people with prior heart attack and inflammatory atherosclerosis, when taken in combination with standard of care therapy.

Canakinumab was originally approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in 2009 for the treatment of cryopyrin-associated period syndromes (CAPS). It is currently sold under the trade name Ilaris.

The new phase III CANTOS results are particularly notable, a Novartis statement said, because despite standard treatment, people with a prior heart attack have a higher ongoing risk of experiencing another event or dying. In about 40% of people who have had a heart attack, that risk is directly related to increased inflammation associated with atherosclerosis.

“Despite current treatment, about 25% 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 of Drug Development and Chief Medical Officer at Novartis. “ACZ885 [canakinumab] 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.”

According to Novartis, full data from the study will be submitted for presentation at a medical congress and for peer reviewed publication later this year.

The Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) is a randomized, placebo-controlled, event-driven phase III study to evaluate the efficacy, safety and tolerability of quarterly subcutaneous injections of canakinumab in combination with standard of care therapy for the prevention of recurrent cardiovascular events.

The study monitored 10,061 people with a prior heart attack and a high sensitivity to C-reactive proteins. Three different doses of canakinumab were evaluated versus placebo.

The primary endpoint was time to first occurrence of major adverse cardiovascular event, which is a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The first secondary endpoint was time to first occurrence of the composite cardiovascular endpoint, which consisted of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalization for unstable angina requiring unplanned revascularization. The second was time to new onset type 2 diabetes among people with pre-diabetes at randomization, the third was time to occurrence of non-fatal myocardial infarction non-fatal stroke or all-cause mortality, and the fourth was time to all-cause mortality.

The study ran for roughly 6 years, with a median follow-up time of 3.8 years.