Regulatory, Setbacks

FDA slaps down Novartis’ blockbuster pitch for canakinumab — so what went wrong?

In a major setback, Novartis used its quarterly earnings report to flag an FDA slapdown on their application to market canakinumab for cardio risk reduction.

Vas Narasimhan

Touted as a blockbuster indication, the pharma giant steered this drug through a big late-stage development program, even pulling out data on a large subgroup of patients that could benefit from the drug. The then development chief Vas Narasimhan was promoted to CEO in part on the success he had with this drug — only to get hit with a complete response letter.

A spokesperson for the company offered an explanation for what went wrong at the FDA:

Based on the correspondence from the FDA, the CANTOS data would not support labeling for the use of canakinumab as a targeted therapy for those patients with cardiovascular disease who achieved a reduction of hsCRP below the 2 mg/L target. At this time, we are evaluating the feedback provided and plans further discussions with the FDA.

That said, we are continuing to study canakinumab to treat non-small cell lung cancer in several Phase 3 studies, with the first trial completion expected in 2022.

The rejection is a particularly bitter pill for Novartis to swallow now, after touting the drug following the collapse of its effort to get their other cardio drug serelaxin approved.

Tim Anderson

The anti-inflammatory drug, sold as Ilaris for a niche market, earned $380 million last year. And considering data on an added risk of infection as well as some experts fretting about the somewhat fuzzy clarity of the benefit initially on display, Tim Anderson pegged the peak sales at a consensus of $800 million, while noting that patent protection should run out in only 7 years.

Other analysts were much more upbeat, with Bank Vontobel offering good odds of $2 billion in peak sales — money Novartis needs to spur revenue growth.

Jefferies’ Michael Yee noted:

Although overall the drug showed a 15% CV benefit on the primary endpoint, based on prior commentary, it is likely NVS was seeking to include the pre-specified sub-group of pts who are able to get to >1.7-2.0mg of hsCRP reduction which led to much larger 25-27% CV benefits. NVS may feel this is the population that has significant benefit and would drive sufficient commercial opportunity rather than the more modest 15% CV benefit in the overall enrolled population. While doc commentary has suggested that NVS would target perhaps a segment (ie 30-40%) of overall high CV risk market (pts who had prior MI too) and not really compete much for the pts taking AMGN PCSK9, it would be keen to watch this as a 25-27% benefit would be compelling for pts in the market…As a reminder, ESPR has also shown a significant 40% reduction in hsCRP as well in its studies which may help add confidence to overall treatment effect in their CVOT study (we look to upcoming important Phase III safety data coming H2 October…if clean and no major imbalances, this could bode well for ESPR).

The treatment is designed to inhibit IL-1ß, a key cytokine, for a prolonged period, tamping down on inflammation to lower risk to patients.

Researchers also pulled out positive subgroup data on gout from the CANTOS study, which tracked more than 10,000 patients for more than 6 years — one of the biggest studies in the pharma giant’s history.

There is a side benefit to this drug that Novartis has been puzzling out. The drug produced a reduction in lung cancer mortality of 77%, underscoring their theory that inhibiting IL-1ß could produce promising data in oncology.


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Scientist, Quality Control
Molecular Templates Austin, TX
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Molecular Templates Austin, TX
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Flagship Pioneering Cambridge, MA

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