Novartis homes in on heart biomarker for canakinumab

When Novartis files canakinumab for cardiovascular disease by the end of the year it will focus on a subgroup of high responders.

While this might help convince the US FDA after a lacklustre result in all-comers earlier this year, the company could still find it hard to win round payers – although a promise to provide the first dose for free, while response is evaluated, could help.

Still, Novartis’s pricing strategy is likely to be closely watched. Canakinumab, trademarked as Ilaris, is already approved in several rare diseases, where it is thought to cost around $200,000 per year.

If the product does get the go-ahead in cardiovascular disease, its price tag will need to be much lower. Different dosing schedules might help facilitate this: in its rare disease indications canakinumab is given monthly, whereas in its cardiovascular disease study it was dosed quarterly.

When asked about pricing plans during an R&D day yesterday, Novartis executives said it was too soon to give details, but its incoming chief executive Vasant Narasimhan added: “If we get the labelling we need, we will price sensibly for a cardiovascular drug.”

On this point, Novartis investors will hope that the company has learned some lessons from the disappointing launch of Entresto.

Pre-planned subgroup

The decision on canakinumab’s label now rests with the regulators. The Novartis execs seemed optimistic that the FDA would look favourably on the drug's latest data, despite the fact that this came from a subgroup analysis of the Cantos trial – albeit a pre-planned one, according to the company.

That study had already found a statistically significant 15% reduction in major adverse cardiovascular events (MACE) with a 150mg dose of canakinumab – something that Mr Narasimhan yesterday admitted would not be compelling enough for payers (ESC 2017 – Cancer death decrease might not save Cantos, August 27, 2017). 

But homing in on the responder subgroup could give Novartis a path forward with canakinumab. A new analysis, presented yesterday at the AHA meeting in Anaheim, California, and published simultaneously in The Lancet, found a 25% MACE reduction in patients on the 150mg dose who had hsCRP levels of below 2mg/l after three months.

This was driven by a 31% reduction in cardiovascular death and a 30% fall in myocardial infarction (MI); the previously reported all-comers benefit primarily came from a reduction in MI.

Around 55% of patients in Cantos – which enrolled post-MI patients with a high inflammatory burden, classed as hsCRP levels of 2mg/l or above – met the newly defined threshold for response. The addressable population is around 260,000 of the 1.3 million post-MI patients in the US and five biggest EU markets, Novartis estimates.

However, Novartis had to work hard to get to this final data package; notably, the threshold for hsCRP response had been set at a different level in a previous analysis. With all this data mining, surely a request from the FDA for a second trial in this indication cannot be ruled out.

Adcom approaching?

Novartis will hope that the agency's seemingly more lenient stance will work in canakinumab’s favour. Mr Narasimhan noted that the agency had been “very open” to the cardiovascular proposal, but did say that an advisory committee meeting was likely.

As for any worries that hsCRP testing could hold back the adoption of canakinumab, the executives pointed out that it was easy to carry out and cheap, at around $1-3 per test. However, analysts attending the R&D day seemed keen on a prospective biomarker of response, something that has so far not been identified.

Cantos also found an intriguing reduction in cancer deaths, particularly lung cancer, but Novartis appears to have given up on any hope of getting these data into the efficacy section of canakinumab’s label, for now at least.

This could change with more oncology data, with three studies set to start in the first half of next year in non-small cell lung cancer. One will assess canakinumab as an adjuvant therapy, one will evaluate the drug in first-line disease in combination with an anti-PD-1 agent, and the other will look at second-line therapy in patients who have relapsed after anti-PD-1 treatment.

With results some way off, however, Novartis’s near-term hopes for canakinumab hinge on success in cardiovascular disease. The company’s decision to focus on a niche looks smart after disappointments with other cardiovascular drugs like the PCSK9 inhibitors – but ultimately the FDA and payers will have the final say on the wisdom of this approach.

To contact the writer of this story email Madeleine Armstrong in London at madeleinea@epvantage.com or follow @ByMadeleineA on Twitter

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