Novartis’s canakinumab cancer test approaches

Will it be a new class of cancer drug or another failure for Novartis’s IL-1 inhibitor?

Novartis’s anti-IL-1 beta antibody canakinumab has already flopped in cardiovascular disease. Soon the company will find out whether its pivot to cancer has paid off, or whether it has thrown good money after bad.

Novartis spent nearly $1.5bn on its efforts in cardiovascular disease, and its cancer bet will amount to much less, according to Evaluate Omnium. Development in non-small-cell lung cancer, the oncology indication in which cana is most advanced, is estimated to come in at a much more manageable $360m.

Project Canakinumab
Company Novartis/Regeneron
Event Data from Canopy-2 and Canopy-1 NSCLC trials
Date H1 2021 & H2 2021, respectively

For Novartis, this seems like a risk worth taking, especially after the intriguing cancer findings reported in the Cantos cardiovascular outcomes study in non-cancer patients at the ESC meeting in 2017: cana was associated with a 67% lower risk of lung cancer incidence and a 77% lower risk of lung cancer death (ESC 2017 – Cancer death decrease might not save Cantos, August 27, 2017).

If anti-IL-1 drugs do turn out to have utility in cancer there is not much competition, with Cantargia’s CAN04 the only mid-stage rival.

The theory is that, in blocking IL-1 beta, cana could inhibit tumour-promoting inflammation. This theory has not yet been properly tested: Cantos was not prospectively designed to evaluate the drug’s effect in cancer, so the trial's findings should be treated with caution. 

Canakinumab is already on the market, sold as Ilaris, for several rare diseases. 

Anti-IL-1 projects in development for cancer
Product Company Description Indication(s)  Trial details & readouts
Phase III
Canakinumab Novartis Anti-IL-1 beta MAb NSCLC  Canopy-2, 2L (NCT03626545), data due H1 2021; Canopy-1, 1L (NCT03631199), data due H2 2021; Canopy-A, adjuvant (NCT03447769), data due 2022
Phase II
Can04 (nidanilimab) Cantargia Anti-IL1RAP MAb Solid tumours inc. pancreatic cancer, NSCLC Ph2 Canfour (NCT03267316), completed Dec 2020; Ph1 Keytruda combo (NCT04452214) completes Jan 2022
Phase I
VPM087 (gevokizumab) Novartis Anti-IL-1 beta MAb (allosteric inhibitor) Colorectal, renal, gastro-oesophageal cancers 1L (NCT03798626), completes Jan 2023
Kineret (anakinra) Swedish Orphan Biovitrum IL-1 antagonist CLL NCT04691765*, completes Apr 2021
*Investigator-sponsored study. Source: EvaluatePharma,

Jefferies analysts only give cana a 40% chance of success in its upcoming cancer trials, pointing out that there is no prior evidence of the drug’s efficacy in metastatic NSCLC, the setting for the Canopy-1 and Canopy-2 studies that are due to read out this year.

The first will be Canopy-2, in second or third-line metastatic NSCLC, with results expected in the first half. Patients in the study, who received cana plus docetaxel or docetaxel alone, had to have failed both PD-(L)1 inhibitors and platinum-based chemo, combined or sequentially.

The trial's chance of success is hard to handicap given the relatively new incorporation of checkpoint inhibitors into front-line standard of care. “The population given front-line IO alone has only just emerged,” Dr Jack West, a lung cancer specialist at the City of Hope Comprehensive Cancer Center, who is not involved in the Canopy trials, told Evaluate Vantage. “We have no data because we have no actual trials published that focus on this population.”

The design of Canopy-2 means it should be easy enough to see whether cana is an improvement over chemo.

Checkpoint approaching

Meanwhile, Canopy-1 should answer the question of whether cana adds anything to checkpoint inhibition, with data due in the second half. The study, in first-line metastatic NSCLC, is testing cana plus Keytruda plus chemo, versus Keytruda plus chemo. It is accepting all comers by PD-L1 status, but will stratify patients accordingly, a spokesperson for Novartis told Evaluate Vantage.

The most bullish case for cana in cancer took a blow last year when an interim analysis of the Canopy-1 study came and went without the trial being stopped early for efficacy.

If Canopy-1 and 2 fail, Novartis might cling to the hope of success in Canopy-A, in the adjuvant setting, where results are expected in 2022. Jefferies notes that even if Canopy-1 and 2 fail, there is a chance for Canopy-A as “reducing inflammation might still be useful in delaying disease progression at an earlier stage of the cancer”.

They put cana’s peak cancer sales at $2bn, helping to explain why Novartis decided to take the plunge here. Regeneron could also get a nice payday: that company receives royalties on cana under a 2009 agreement that also covers new indications, and the royalty rate would go up to 15% if annual sales exceed $1.5bn.

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