Experimental drug shows evidence of lowering cholesterol, reducing risk of cardiovascular disease, and potentially treating lung cancer.
Novartis recently released data from the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), which explored the efficacy of ACZ885 in patients with a history of heart attack and inflammatory atherosclerosis, measured by high-sensitivity C-reactive protein (hsCRP).
The results of a planned analysis showed that ACZ885 may reduce the rate of lung cancer and associated mortality, according to a press release. The results of the study, published by The Lancet,were reviewed by independent oncologists and presented at the European Society of Cardiology Congress.
While the effects were observed to be dose-dependent, Novartis reported that treatment with ACZ885 reduced the relative risk of lung cancer by 67% and lung cancer mortality by 77%. These patients received 300-mg of the drug every 3 months.
"The results of CANTOS are exciting because we now have clear evidence that in addition to lowering cholesterol, targeting inflammation reduces patients' risk of cardiovascular disease, and perhaps even lung cancer," said Paul Ridker, MD, CANTOS study chairman and director of the Center for Cardiovascular Disease Prevention at Brigham and Women's Hospital. "From a cardiologist perspective, these findings represent a novel approach to the treatment of heart disease with the potential to also help patients with certain cancers."
ACZ885 is an interleukin (IL)-1ß antibody. The IL-1ß cytokine is known to continue the progression of inflammatory atherosclerosis, according to Novartis. By inhibiting the cytokine through ACZ885, the CANTOS study aimed to determine whether the drug could stop the progression of cancer.
"By targeting the IL-1ß pathway, CANTOS study findings provide further insights into the role of inflammation in lung cancer and medical researchers additional data to conduct trials to prove this important hypothesis," said Howard A. "Skip" Burris, MD, president of Clinical Operations and chief medical officer, Sarah Cannon Research Institute and chair of the CANTOS Cancer Adjudication Committee.
More than 10,000 patients were enrolled in the CANTOS study. Patients with a history of atherosclerosis with a hsCRP level of >=2mg/L and who never had cancer received either placebo or 1 of 3 doses of ACZ885 (50-mg, 150-mg, and 300-mg subcutaneously every 3 months) in addition to standard therapies, including statins.
The investigators found that ACZ885 resulted in the reduction in hsCRP of 26% to 41% and a reduction in IL-6 of 25% to 43%, according to the release.
ACZ885 300-mg also reduced cancer-related morality significantly compared with placebo. Lung cancer incidence was reduced at both the 150-mg dose and 300-mg dose versus placebo.
Novartis reported that overall rates of adverse events (AEs) and discontinuations due to AEs were similar between ACZ885 and placebo, suggesting the drug may be safe for this patient population, according to Novartis.
"These data are a significant milestone because they show that selectively targeting inflammation with ACZ885 reduces cardiovascular risk and that ACZ885 may also be an important immuno-oncology therapy targeting IL-1ß for lung cancer," said Vas Narasimhan, global head, Drug Development and chief medical officer, Novartis. "We look forward to submitting the CANTOS cardiovascular data to regulatory authorities for approval and initiating additional phase III studies in lung cancer.”