Novartis canakinumab (ACZ885) reduced cardiovascular risk by 25 percent in subgroup of CANTOS Phase III trial participants.
Novartis announced results from a new analysis of the Phase III CANTOS study presented by Dr. Paul Ridker at the American Heart Association (AHA) Scientific Sessions 2017 and published simultaneously in The Lancet.1
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 percent reduction in major adverse cardiovascular events (MACE) versus placebo (HRadj=0.75, 95 percent CI 0.66-0.85, p<0.0001).1
The patients also had a significant reduction of 31 percent in the rate of cardiovascular (CV) death (HRadj=0.69, 95 percent CI 0.56-0.85, p=0.0004) and all-cause death (HRadj=0.69, 95 percent CI 0.58-0.81, p<0.0001).1 There was no significant reduction in these endpoints observed among those treated with canakinumab who achieved hsCRP levels equal to or above 2mg/L.1
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.2,3 It also demonstrates that treating inflammation in addition to lowering cholesterol may significantly reduce the risk of recurrent CV events.1
“This CANTOS analysis suggests that the initial biologic response to canakinumab may provide a simple method to identify which patients are most likely to obtain long-term benefits,” said Dr. Paul Ridker, M.D., CANTOS study chairman and director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital. “Importantly, these data also support the value of targeting inflammation when treating patients who have had a heart attack in the past, reinforcing that ‘lower is better’ when it comes to levels of inflammation.”
The analysis also evaluated the number of patients needed to treat (NNT). NNT is an epidemiological measure used to communicate the effectiveness of a healthcare 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.
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.1 As previously announced, initial data from the CANTOS study showed that quarterly treatment with 150mg canakinumab resulted in a statistically significant 15 percent reduction in MACE — a composite of CV death, non-fatal myocardial infarction, and stroke — in people with a prior heart attack and inflammatory atherosclerosis.3
Pending final regulatory discussions, Novartis plans to file CANTOS CV data for regulatory approval in Q4 2017.
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References:
1 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.
2 AHA. Invasive Tests and Procedures. Available at: https://www.heart.org/HEARTORG/Conditions/HeartAttack/SymptomsDiagnosisofHeartAttack/Invasive-Tests-and-Procedures_UCM_303931_Article.jsp#.WUlhC-vythF. Last accessed June 2017.
3 Ridker PM, et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017.
(Source: Novartis Pharmaceuticals Corp. via PR Newswire)
Filed Under: Drug Discovery
