A First: Novartis AG Drug May Prevent Heart Attacks and Cut Lung Cancer Risk Too

August 28, 2017
By Alex Keown, BioSpace.com Breaking News Staff

BASEL, Switzerland -- An anti-inflammatory drug developed for cardiac patients has an exciting, yet unintended side effect – possible prevention of lung cancer.

Earlier this summer, Novartis AG said its Phase III drug candidate ACZ885 (canakinumab) was able to lower the risk of significant adverse cardiovascular events in patients by 15 percent in people who have already survived a heart attack and inflammatory atherosclerosis. Trial participants received either placebo or one of three doses of ACZ885 in combination with current standard of care therapies, with 91 percent of them taking lipid-lowering statins, Novartis said. ACZ885 (canakinumab) is a selective, high-affinity, fully human monoclonal antibody that inhibits IL-1ß, a key cytokine in the inflammatory pathway known to drive the continued progression of inflammatory atherosclerosis.

Now though researchers are suggesting it has an added benefit in preventing lung cancer. Data shows that ACZ885 may also be an important immuno-oncology therapy targeting IL-1ß for lung cancer, Novartis’ Chief Scientific Officer Vas Narasimhan said in a statement.

Narasimhan said the company plans to initiate a new Phase III trial based on its early findings to see how the drug does in the lung cancer setting. Novartis is already planning on seeking regulatory approval of ACZ885 in the cardiovascular setting.

The Phase III CANTOS trial took four years to complete. It was one of the longest trials Novartis conducted. In addition to testing the drug in patients with a prior heart attack and inflammatory atherosclerosis, researchers led by Paul Ridker, Director of the Center for Cardiovascular Disease Prevention at Brigham and Women's Hospital, also wanted to look at the possible effects of the drug on cancer risk as well, Stat News noted. In an interview with Stat, Ridker said as an inflammation specialist he knew the NLRP3 pathway increases the risk of cancer, including non-small cell lung cancer. He said there has been a hypothesis that “inflammation of the tumor microenvironment plays a role in the growth and metastases of tumors.” That was why, he told Stat, that Novartis decided to include an oncological arm to the study.

Varying doses of the drug resulted in significant de-risking of lung cancer. At the lowest dose, lung cancer rates dropped 26 percent, Stat reported. The medium dose saw lung cancer risks drop 39 percent and at the highest dose the risk of lung cancer fell at an impressive 67 percent. Not only that, but the patients who received the highest dosing of ACZ885 also had “half the rate of overall cancer death” in comparison to placebo patients.

The Phase III CANTOS study included more than 10,000 patients and took approximately six years. The primary endpoint of the study was time to first occurrence of major adverse CV event (MACE), a composite of cardiovascular death, non-fatal MI, and non-fatal stroke. Additional positive benefit observed in the CANTOS study was a reduction in the number of patients requiring unplanned revascularization for worsening chest pains.