New data shows 31% reduction in CardioVascular death with canakinumab

Announced at the American Heart Association (AHA) Scientific Sessions 2017 and published simultaneously in The Lancet.

The pre-planned secondary analysis of an exploratory endpoint showed that people with a prior heart attack who achieved hsCRP levels below 2mg/L at three months after the first dose of canakinumab had a 25% reduction in major adverse cardiovascular events (MACE) versus placebo (HRadj=0.75, 95% CI 0.66-0.85, p<0.0001). These patients also had a significant reduction of 31% in the rate of cardiovascular (CV) death (HRadj=0.69, 95% CI 0.56-0.85, p=0.0004) and all-cause death (HRadj=0.69, 95% CI 0.58-0.81, p<0.0001). There was no significant reduction in these endpoints observed among those treated with canakinumab who achieved hsCRP levels equal to or above 2mg/L. This analysis indicates that on-treatment hsCRP testing may offer a quick and reliable way to identify the patients most likely to achieve the greatest benefits from long-term canakinumab treatment. It also demonstrates that treating inflammation in addition to lowering cholesterol may significantly reduce the risk of recurrent CV events.The analysis also evaluated the number of patients needed to treat (NNT). NNT is an epidemiological measure used to communicate the effectiveness of a health-care intervention in which the lower the NNT, the more effective the intervention.

The estimated NNT of the subgroup of patients was 16, indicating that 16 patients treated with canakinumab whose hsCRP values dropped below 2mg/L would need to be treated for five years to prevent one death, heart attack, stroke or coronary revascularization. The NNT for the CANTOS cohort as a whole was 24. Canakinumab has been shown to have major effects on inflammation, which is associated with atherothrombosis, the main cause of acute coronary syndromes and CV death. People with elevated inflammatory biomarkers, such as hsCRP (high-sensitivity C-reactive protein), are at an increased risk of CV events. The hsCRP test is a simple, inexpensive and widely available blood biomarker test that may also be used for residual inflammatory risk. This subgroup analysis by Dr. Paul Ridker included patients whose level of hsCRP at three months was 2mg/L or greater, as well as those whose level was less than 2mg/L, which is a commonly used clinical cut point for hsCRP measuring residual inflammatory risk. The analysis supports that patients who achieve an hsCRP level of less than 2mg/L by the third month on treatment may receive the greatest benefit from long-term treatment with canakinumab. The safety profile of canakinumab in the subgroup of patients whose hsCRP levels dropped below 2mg/L was consistent with the overall study population.

The overall rates of adverse events (AEs), serious AEs, and discontinuations due to AEs in CANTOS were similar to placebo across all canakinumab doses. There was no relationship between on-treatment hsCRP levels and adverse events. With more than 10,000 patients enrolled in the study over six years, CANTOS was one of the largest and longest-running clinical trials in Novartis history. As previously announced, initial data from the CANTOS study showed that quarterly treatment with 150mg canakinumab resulted in a statistically significant 15% reduction in MACE - a composite of CV death, non-fatal myocardial infarction, and stroke - in people with a prior heart attack and inflammatory atherosclerosis. Pending final regulatory discussions, Novartis plans to file CANTOS CV data for regulatory approval in Q4 2017.

See- Ridker PM, et al. "Relationships of C-Reactive Protein Reduction to Cardiovascular Event Reduction Following Treatment with Canakinumab: Analyses from the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS)". The Lancet. 2017.