Canakinumab Study Fails to Meet Primary Endpoint

Novartis announced new data from an interim analysis for the randomized, double-blind, placebo-controlled CAN-COVID trial evaluating the efficacy and safety of canakinumab in hospitalized patients with COVID-19 pneumonia and cytokine release syndrome (CRS). The ongoing trial failed to meet its primary endpoint showing that treatment with canakinumab plus standard of care (SoC) did not demonstrate a significantly greater chance of survival for patients without the need for invasive mechanical ventilation, compared with placebo plus SoC up to Day 29. The trial did not meet its key secondary endpoint of reducing the COVID-19-related death rate during the 4-week period after treatment. The safety profiles of canakinumab plus SoC and placebo plus SoC were comparable.

“Though the CAN-COVID trial did not show the patient benefit we were hoping for, it helps improve the scientific understanding of COVID-19 and the role of interleukin-1β inhibition,” said John Tsai, M.D., Head of Global Drug Development and Chief Medical Officer for Novartis. “There’s still an urgent need for effective ways to combat COVID-19 and we will continue to apply our best scientific minds in support of the global pandemic response, including a Phase III trial of ruxolitinib. We’re deeply grateful to the patients who participated and their caregivers, as well as the healthcare professionals and hospital staff who made this research possible while fighting the pandemic on the front line.”

In the trial, the primary endpoint of survival without the need for mechanical ventilation was 88.8% for canakinumab plus SoC vs 85.7% for placebo plus SoC (P=0.29). The key secondary endpoint of COVID-19-related mortality up to 4 weeks was 4.9% for canakinumab plus SoC vs 7.2% for placebo plus SoC (P=0.33). Both the primary and key secondary endpoints trended in favor of canakinumab but did not reach statistical significance. No new safety signals for canakinumab were identified.

This interim analysis will be submitted to a peer-reviewed journal in the coming weeks. The CAN-COVID results do not affect any other ongoing trials for canakinumab, including investigations for the treatment of non-small cell lung cancer (NSCLC).

As part of its continued efforts to support the global pandemic response, Novartis in October announced a collaboration with Switzerland-based Molecular Partners to develop two DARPin® therapies designed for potential use against COVID-19. In addition, a Phase III trial for ruxolitinib in COVID-19 is ongoing, with preliminary results expected by year end.

CAN-COVID is a Phase III, multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of canakinumab plus standard of care (SoC) in hospitalized patients with COVID-19 pneumonia and cytokine release syndrome (CRS). Patients were hypoxic but not requiring intubation or invasive mechanical ventilation. The primary endpoint was to demonstrate the benefit of canakinumab plus SoC vs placebo plus SoC in increasing the chance of survival without the need for invasive mechanical ventilation up to Day 29. The key secondary endpoint was to reduce the COVID-19-related death rate during the 4-week period after trial treatment6. The trial enrolled 454 patients at multiple centers across the US, Russia and Europe. Both endpoints were analyzed at Day 29. The average age of trial participants was 58 years old, ranging from 18 to 98 years old. Approximately 30% were Hispanic or Latino, 16% were Black or African American and 4% were Asian. Interim analysis of Day 29 results is available. The trial is ongoing (to Day 127) with full results expected in early 2021.

Canakinumab is biologic medicine used in the treatment of a number of rare, debilitating auto-inflammatory diseases, for which there are limited options available. It is a monoclonal antibody that binds to and neutralizes interleukin-1 beta (IL-1β), blocking its action. Excessive production of IL-1β plays a prominent role in certain inflammatory diseases and immune responses. Canakinumab is an established medicine approved under the trade name Ilaris® in approximately 60 countries including the US, Europe and others. It is indicated for rare conditions including periodic fever syndromes, adult-onset Still’s disease (AOSD) and systemic juvenile idiopathic arthritis (SJIA). First approved in 2009, canakinumab has been proven to be highly effective and well tolerated as a treatment option for its approved indications based on previously reported clinical trials. As well as being studied in severe COVID-19, canakinumab is also being investigated for the treatment of a number of other diseases involving inflammation, including non-small cell lung cancer (NSCLC).