Novartis announces analysis published in The Lancet showing ACZ 885 (canakinumab) reduced the rate of lung cancer mortality among study participants by 77%.

Novartis has revealed primary data from the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), a Phase III study evaluating the role of ACZ 885, an interleukin-1beta antibody, in people with a prior heart attack and inflammatory atherosclerosis as measured by high-sensitivity C-reactive protein (hsCRP), a known marker of inflammation, at levels of more than=2mg/L. An additional pre-planned analysis showed that ACZ 885 reduced the rate of lung cancer incidence and mortality among study participants. Effects were dose-dependent with a relative risk reduction of 67% finding for lung cancer (HR 0.33 [95% CI: 0.18-0.59]) and 77% for lung cancer mortality (HR 0.23 [95% CI: 0.10-0.54]) observed among patients receiving the 300mg dose of ACZ 885 every three months. As part of the study design, all cases of cancers were reviewed by an independent panel of oncologists unaware of study drug allocation. Details of the lung cancer analysis were presented alongside the cardiovascular outcomes data, at the European Society of Cardiology (ESC) Congress and published simultaneously in The Lancet. The details of the cardiovascular findings were also presented at ESC and simultaneously published in The New England Journal of Medicine.

With more than 10,000 patients enrolled in the study over the last six years, CANTOS was one of the largest and longest-running clinical trials in Novartis' history. Trial participants with a prior history of atherosclerosis, a hsCRP level of more than =2mg/L, and who were free of previously-diagnosed cancer, received either placebo or one of three doses of ACZ 885 (50mg, 150mg, and 300mg subcutaneously every 3 months). All participants received current standard of care therapies, with 91% of participants taking lipid-lowering statins. During a median follow up of 3.7 years, as compared to placebo, ACZ 885 resulted in dose dependent reduction in hsCRP of 26 to 41% and a dose-dependent reduction in IL-6 of 25 to 43% (p=<0.0001). for all cancer related mortality n="196" across treatment acz 885 resulted in a significant reduction compared to placebo at the 300mg dose hr 0.49: 95 ci: 0.31-0.75 p="0.0009)." incident lung cancer n="129" across treatment was reduced at the 300mg dose versus placebo hr 0.33 95 ci: 0.18-0.59 p=""><0.0001) and the 150mg dose versus placebo hr 0.61 95 ci: 0.39-0.97 p="0.034)." lung cancer mortality was significantly less common at the 300mg dose versus placebo hr 0.23 95 ci: 0.10-0.54 p="0.0002)." the overall rates of adverse events aes serious aes and discontinuations due to aes were similar to placebo across all acz 885 doses. in the six year-long study serious infections were reported in 11.7 vs 10.2 and malignancies were reported in 6.7 vs 7.1 of participants acz 885 300mg vs placebo respectively. fatal infections occurred in about one per 1000 patients in placebo. although rare this occurrence was higher in the combined acz 885 group than placebo. on the other hand cancer deaths were cut in half by acz 885 such that there was a non-significant reduction in death from any cause.>

"These data provide proof that inflammation inhibition, in the absence of lipid lowering, can improve atherothrombotic outcomes and potentially alter the progression of some fatal cancers," said the lead researcher Paul Ridker of the Brigham and Women�s Hospital, Boston.

Comment: Canakinumab (ACZ 885) can lower the risk of lung cancer as well as cardiovascular disease by reducing inflammation according to the data from the CANTOS study. Researchers say the findings are a validation of the inflammation hypothesis in atherosclerosis, ushering in a new era in cardiovascular disease prevention, and at the same time opening up new possibilities in cancer treatment.

See- "Effect of interleukin-1 beta inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial."- Prof Paul M Ridker, MD, Jean G MacFadyen, BA, Tom Thuren, MD, Brendan M Everett, MD, Prof Peter Libby, MD,, Prof Robert J Glynn, ScD on behalf of the CANTOS Trial Group. Published: 27 August 2017 DOI: http://dx.doi.org/10.1016/S0140-6736(17)32247-X.