Novartis' closely watched canakinumab hits a snag in lung cancer. What's next for the anti-inflammatory drug?

Novartis headquarters
Novartis' canakinumab, sold in inflammatory diseases under the brand Ilaris, failed a phase 3 test in previously treated non-small cell lung cancer. (Novartis)

First it was heart disease, now it’s non-small cell lung cancer (NSCLC). Novartis can’t seem to make its canakinumab injection work outside immunology, where the drug’s currently sold as Ilaris.

The interleukin-1 beta (IL-1beta) inhibitor, used in tandem with chemotherapy, didn’t top solo chemo at extending the lives of previously treated NSCLC patients whose disease had progressed on one platinum-based chemo and one PD-1/L1 inhibitor, Novartis said Tuesday.

Despite this phase 3 Canopy-2 failure, the data provide “valuable insights into IL-1beta inhibition,” John Tsai, M.D., Novartis’ chief medical officer, said in a statement. Details from this trial will be shared at an upcoming medical meeting.

Jefferies analyst Peter Welford put his money on earlier lines of use, especially in post-surgery patients. He forecasts $2 billion in peak canakinumab sales based on a 40% probability that it will succeed in earlier-stage disease.

Two other phase 3 trials remain ongoing for canakinumab in NSCLC. The Canopy-1 study is evaluating whether adding canakinumab to current standard of care—Merck & Co.’s PD-1 megablockbuster Keytruda plus chemotherapy—can stave off cancer progression or improve survival in newly diagnosed NSCLC patients. That study passed an interim analysis last fall without reading out a definite answer, so it will continue with top-line data now expected in the second half of 2021.

The Canopy-A trial is evaluating canakinumab as an adjuvant therapy to see if it can prevent cancer from returning for NSCLC patients who’ve had their tumors surgically removed. And a phase 2 nonregistrational trial dubbed Canopy-N is looking at the pairing of canakinumab and Keytruda as a pre-surgery therapy.

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Novartis launched the Canopy NSCLC programs in 2018 after noticing a significantly lower-than-expected rate of lung cancer death among heart failure patients in the drug’s phase 3 Cantos cardiovascular trial. At the highest, 300-mg dose tested, canakinumab patients had a 51% lower rate of death from any cancer compared with the placebo group, with the reduction in lung cancer death at 77%.

IL-1 has previously been linked to the progression and aggressiveness of lung cancer. Novartis argues that by targeting IL-1beta, canakinumab could potentially inhibit pro-tumor inflammation that may drive cancer-promoting mechanisms while suppressing anti-tumor immune responses.

Treating cancer by reducing inflammation remains a novel territory, Welford noted in a report Tuesday. So he previously had low expectations that the Canopy-2 trial would succeed, given the patients’ advanced disease, plus the fact that the Canopy-1 trial didn’t yield a strong enough efficacy signal at its interim analysis. But he suspects reducing inflammation with canakinumab might yield greater benefit earlier in the course of the disease.

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Ilaris is currently approved in several inflammatory diseases, mostly rare ones, with 2020 sales of $873 million after 30% year-over-year growth.

Novartis previously tried to position canakinumab as a treatment for certain patients who have had a prior heart attack based on results from the Cantos trial. But the FDA rejected that filing in 2018 for insufficient data, and Novartis subsequently withdrew the application from the European Medicines Agency.

The Swiss pharma recently tried to pivot the med to COVID-19 as a potential therapy for controlling a dangerous inflammatory response called cytokine release syndrome in hospitalized patients. But the CAN-COVID trial found that adding the drug to standard of care didn’t reduce the need for invasive ventilation or COVID-19-related death.