ORLANDO, Fla.—When Novartis released results from a 10,000-patient trial examining canakinumab—already approved as rare disease med Ilaris—last year at the European Society of Cardiology, analysts initially questioned what its future might hold as a cardio drug. Now, the drugmaker is touting two subanalyses from the trial to help outline what that future might look like.
In short, it looks like a therapy for the highest-risk patients—and Novartis will work with payers to win reimbursement for those groups.
In two analyses—one in patients with chronic kidney disease and the other in diabetes—canakinumab "substantially" reduced the risk of major adverse cardiovascular events, Brigham and Women's Hospital researchers said this week at the American College of Cardiology conference in Orlando. Both groups of patients are at higher risk of heart attack, stroke and other cardiovascular complications.
In chronic kidney disease patients, the drug reduced the risk of events by 18% over placebo. For patients with diabetes, canakinumab cut risks by 10% in a composite measure of CV events, known as MACE, while those with prediabetes experienced a 14% risk reduction.
Still, the drug didn't prevent prediabetes patients from progressing to diabetes, according to ACC, which was a key secondary endpoint in the large Cantos trial.
Canakinumab works by suppressing inflammation, which is increasingly linked to a range of diseases, from cancer to heart disease as well as the more obviously inflammatory conditions such as rheumatoid arthritis. Investigators did the substudies to further explore the drug's profile in patients with the largest need for treatment, Novartis head of CV development David Soergel told FiercePharma Monday.
"Chronic kidney disease and diabetes are both inflammatory diseases; that was the idea behind looking at these populations within Cantos," he said.
Ilaris is already FDA-approved to treat certain rare inflammatory diseases, but Novartis conducted Cantos—a massive study in patients who had a prior heart attack and residual inflammatory risk—to test its merit as a CV therapy. Patients received the injection in addition to lipid-lowering drugs, and the entire group saw a 15% reduction in risks of a major CV event.
When that data were presented last summer, analysts were underwhelmed, partly because canakinumab patients suffered a higher risk of infections when compared to placebo. An accompanying editorial in the New England Journal of Medicine suggested the drug's benefits were unclear.
Then in November, the company presented data showing that patients with high-sensitivity C-reactive protein levels below 2 milligrams per liter three months after receiving canakinumab saw a 25% risk reduction in major adverse cardiovascular events—again compared with placebo—plus a 31% reduction in cardiovascular deaths and all-cause mortality.
At the time, Novartis CEO Vas Narasimhan said a "a simple test at three months can identify the patients who would benefit most, and that in general, lower (hsCRP) is better." In a new Fortune op-ed, Narasimhan called on drugmakers to better apply precision medicine in cardiovascular disease, citing how cancer drug testing has become increasingly targeted.
Now, Novartis is back with the new analyses in chronic kidney disease and diabetes. The company has already submitted an application for a new FDA nod, and it will "engage with payers, regulators, policymakers" on ways to use all the evidence to "optimize the delivery of the medicine," Soergel said Monday at ACC.
"We're particularly interested [that] patients who derive the greatest benefit and also have the highest unmet need have access to the medicine," he said. "When we run a 10,000-patient trial like Cantos, and we find a responder population like we have, we will be having conversations proactively about that with the [FDA]."
A key issue is pricing. If canakinumab does win approval as a mass-market drug, the company would likely have to change its pricing strategy from the current indication; in rare diseases, higher-priced treatments are common. Soergel said for patients that see the most benefit, the company would "have a conversation about ensuring patient access." As industry watchers know, payers have gotten tough on recent CV launches such as PCSK9 cholesterol drugs from Amgen, Sanofi and Regeneron and Novartis' own Entresto.