ESC: Novartis faces an uphill battle turning niche drug Ilaris into a cardio blockbuster

For 6 of the last 10 years that Novartis’ canakinumab has been available, the company has been conducting a study designed to vastly expand the market for the drug, which is currently sold under the name Ilaris to a small group of patients with rare inflammatory diseases.

On Sunday, Novartis presented data from that study at the European Society of Cardiology (ESC) Congress, and now it plans to seek FDA approval for use of the drug to reduce the risk of major cardiovascular events in patients with prior heart attack and atherosclerosis. But the data—which included a surprise anticancer effect—raised doubts among analysts about what, exactly, the future of canakinumab might be.

During the trial, known as Cantos, patients treated with the second-highest dose of canakinumab showed a 15% reduction in the risk for major cardiovascular events. Investigators also observed a 10% reduction in the risk of cardiovascular death.

Lowering cancer risk wasn’t an endpoint of the study, but during a safety analysis the company discovered a 77% reduction in deaths from lung cancer and a 67% drop in lung cancer diagnoses among patients on the highest of the three doses of canakinumab that were tested.

Novartis plans to seek FDA approval for use of the drug in patients with prior cardiovascular events in the fourth quarter of this year. And it’s starting discussions with the agency about how it might pursue an additional approval in the oncology setting. The company’s ultimate goal is to greatly expand sales of the drug, which is expected to bring in only about $380 million this year.

But analysts were underwhelmed by the CANTOS results, particularly in the context of the side effects reported during the study. They included a risk of fatal infections that was higher in patients taking canakinumab than it was in the placebo group. Futhermore, when the cardiovascular and cancer data were published simultaneously in the New England Journal of Medicine and The Lancet respectively, they were both accompanied by editorials suggesting an unclear clinical benefit in either indication.

Thus the consensus estimate that canakinumab will only reach peak sales of $800 million "may not change very much" predicted Bernstein analyst Tim Anderson after the ESC presentation. Further complicating the issue, he added, is that the drug loses patent protection in 2024, severely limiting the timetable for Novartis to reap any meaningful benefit from an expanded market.

One bright point in the data was that the drug produced a significantly higher benefit in a particular subgroup of patients. During the trial, investigators measured levels of an inflammatory marker called high-sensitivity C-reactive protein (hsCRP). They discovered that half of patients who achieved lower-than-median hsCRP levels after the first injection of canakinumab had a 27% reduced risk of major cardiac events.

Then there was the cancer benefit. Canakinumab acts by targeting an inflammatory pathway known as interleukin 1 beta (IL1b). Inflammation can affect tumor formation, growth and spread, so the reduction in lung cancer mortality adds fuel to the hypothesis that targeting inflammation could be a viable approach to treating and preventing cancer, Novartis executives believe. They intend to talk to the FDA about including a cancer indication on the cardiovascular label for the drug, as well as pursuing a separate oncology indication.

"The biological rationale for neutralizing interleukin 1 beta is equally strong in cancer formation … as well as in the treatment of advanced malignancy," said Jay Bradner, president of the Novartis Institutes for BioMedical Research, in a media conference call held during ESC. Studying the mechanism as a monotherapy as well as in combination with immuno-oncology approaches "has an equally compelling potential," he said.

Still, even if the cardiovascular and oncology indications pan out, questions remain about whether Novartis will be able to slap a high enough price on canakinumab to fully realize its blockbuster potential. The company won’t offer any hints on pricing at this point, though Novartis Chief Medical Officer Vas Narasimhan said during the media call that he thinks the new data will give Novartis plenty of leeway. "In view of the additional oncology findings, we don’t think you should just think of this as a cardiovascular drug per se," he said.

Ilaris, with its current orphan indications, costs $64,000 a year—a price that may work in oncology but that will most likely run into resistance in the cardiovascular world. Witness the brouhaha that ensued over Amgen’s PCSK9 cholesterol drug Repatha and Sanofi and Regneron’s similar Praluent, both of which cost more than $14,000 a year. The companies have faced plenty of backlash from payers, and the Institute for Clinical and Economic Review (ICER) said Repatha is worth only $5,404 to $7,735. Then, in June of this year, ICER looked at Amgen’s cardiovascular outcomes data and said Repatha may not even be worth that much.

So what’s the bottom line for canakinumab? The ambitious CANTOS study program turned out results that are interesting, but may not be so lucrative.

"The bet paid off scientifically, and opens up wider two new fields of additional research—the role of inflammation in CV disease, and the potential role of IL1b in cancer," wrote Sanford Bernstein’s Anderson in a note to investors. "But the direct commercial payoff, in terms of higher canakinumab sales, will probably remain elusive."