Event – Novartis hopes Cantos will not cause more heartache
Novartis’s cardiovascular strategy, already under question after the recent serelaxin failure and lacklustre Entresto launch, will come under further scrutiny with the readout of its Cantos trial of Ilaris in mid-2017.
Hopes are not high for the study, which is testing whether the IL-1β inhibitor reduces the risk of cardiovascular events in patients who have had a heart attack. The theory that targeting inflammation could decrease cardiovascular risk is an enduring one, but so far it has not been proven.
Analysts are not confident that Cantos will be any different from the trials that have gone before it, with Berenberg only giving the study a 10% chance of success.
Novartis already markets Ilaris, but so far the drug is only approved in rare disorders, with sales of just $283m in 2016. Previous efforts to expand into rheumatoid arthritis and gout have fallen short.
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The product could still become a blockbuster if Cantos does report positive results, with the Berenberg analysts forecasting revenues of $4.4bn if the cardiovascular indication is approved.
This is a big if, and failure would leave Novartis trying to justify its investment in another large outcomes trial, especially coming so soon after the serelaxin miss in the Relax-AHF-2 study (Serelaxin setback puts focus on Entresto, March 22, 2017).
That was a blow to the Swiss firm's credibility: Bernstein noted that this was the second time serelaxin had disappointed, the first being its 2014 rejection by the FDA. “Both times Novartis was loudly confident in serelaxin's chances. And both times Novartis got it wrong,” they wrote.
If the company has erred again with Ilaris and Cantos this will hit investor sentiment further and heap even more pressure on Entresto, its underperforming heart failure pill.
Yes we Cantos?
Novartis will hope that it does not come to that. Cantos is testing Ilaris dosed at 50mg, 150mg or 300mg every three months versus placebo in over 10,000 post-myocardial infarction patients with persistent elevation of high-sensitivity C-reactive protein (hsCRP), defined as over 2mg/l.
The primary endpoint is the time to first occurrence of a major adverse cardiovascular event, which is a composite of cardiovascular death, non-fatal MI and stroke.
Earlier data are not too promising: phase II trials found that Ilaris lowered levels of the inflammatory markers CRP and IL-6, but also led to a 10% increase in blood triglycerides at higher doses, a potentially negative cardiovascular risk signal.
The Cantos results should also give a clue about the fate of a similar investigator-led trial, Cirt. That study, which is sponsored by the US National Heart, Lung and Blood Institute, is evaluating low-dose methotrexate – another drug with anti-inflammatory effects – in 7,000 post-MI patients with type 2 diabetes or metabolic syndrome, with a similar primary endpoint.
Cirt has a primary completion date of December 2018, according to Clinicaltrials.gov.
Ultimately, Cantos is a high-risk/high-reward bet for Novartis. Most seem convinced that it will not pay off – but if it does, against the odds, the company’s other cardiovascular missteps might be forgiven.