- A rare disease drug made by Swiss pharma Novartis AG proved effective in preventing cardiac attacks by reducing inflammation levels, a finding that could open up new possibilities to treating heart disease beyond lowering cholesterol or cutting blood pressure.
- Results from a large trial of canakinumab, currently marketed by Novartis as Ilaris for several inherited diseases, showed the drug significantly reduced cardiovascular risk by 15% compared to placebo. Intriguingly, canakinumab also appeared to prevent deaths from lung cancer, although more studies will be needed to corroborate that effect.
- Novartis said it plans to seek regulatory approval for canakinumab as a heart treatment this year. Yet the drug's current high cost — roughly $200,000 a year in the U.S. to treat a rare childhood form of arthritis — would make use prohibitively expensive in a broader population. Safety concerns tied to a higher rate of serious infection could also temper interest.
For years, targeting inflammation has been a way to treating cardiovascular disease, in addition to well-validated approaches such as lowering cholesterol levels. Yet there are no strictly anti-inflammatory drugs currently approved for atherosclerosis. Other heart drugs that reduce inflammation also have effects which could account for the observed benefits.
In a bid to prove this inflammatory hypothesis, the pharma giant tested canakinumab in one of its longest running and largest clinical studies, dubbed CANTOS. Over 17,000 patients were screened and more than 10,000 enrolled in a trial that lasted six years.
Novartis focused on patients who had a prior heart attack and inflammatory atherosclerosis, screened using a biomarker known as C-reactive protein (CRP). Patients were randomized to three doses of canakinumab or placebo and followed for a median of 3.7 years.
Those on the 150 mg dose of canakinumab saw a statistically significant 15% relative risk reduction of a composite of major adverse cardiovascular events (nonfatal myocardial infarction, nonfatal stroke or cardiovascular death).
That benefit was mainly driven by a 24% lowering in the risk of heart attack. Fewer patients treated with canakinumab died than in the placebo group, but that result was not statistically significant.
Despite the landmark results, some cautioned the benefit seen might not be enough to regularly add canakinumab into the rotation of drugs used to treat heart disease.
"The modest absolute clinical benefit of canakinumab cannot justify its routine use in patients with previous myocardial infarction until we understand more about the efficacy and safety trade-offs and unless a price restructuring and formal cost-effectiveness evaluation supports it," wrote Robert Harrington, chairman of the Stanford University Department of Medicine, in a corresponding editorial in The New England Journal of Medicine.
With canakinumab, Novartis faces a challenging decision. The drug is currently priced for a rare disease market and has had some success: sales rose by 20% to $283 million last year. While canakinumab would be dosed less frequently (once a quarter) for treating heart disease, the list price as it stands would likely be a non-starter for the mass market. Yet, repricing could complicate marketing the drug for its rare disease indications.
Jeffrey Holford, an analyst at Jefferies, believes the CANTOS study results could drive net peak sales of over $3 billion for canakinumab — even after factoring in $500 million in lost revenue from Ilaris rare disease sales due to a price reduction.
Not just a cardiovascular drug
Novartis noted canakinumab's benefit was even greater in a sub-group of patients who quickly responded to the drug after one injection. For those patients, treatment with 150 mg of canakinumab led to a 27% relative risk reduction compared to placebo.
Vas Narasimhan, Novartis' chief medical officer, said on a call with reporters Saturday that the pharma would focus on this subgroup in its discussions with regulators about expanding canakinumab's label.
But it's the lung cancer finding that could change the company's calculus the most. Over the course of the study, patients taking the highest dose of canakinumab were at a 67% lower risk of developing lung cancer and an even higher 77% lower risk of dying from lung cancer compared to the placebo group.
Canakinumab inhibits an inflammatory cytokine called interluekin-1 beta (IL-1ß) that is thought to play a role in cancer progression and metastases. Novartis believes that by blocking IL-1ß, canakinumab may have an effect on undetected or undetectable cancers.
The results, though exciting, will need to be confirmed by further study. Novartis plans to launch a Phase 3 trial of canakinumab in non-small cell lung cancer in the first quarter of next year, with further trials in other inflammation-driven cancers to follow.