tetano
Editor, Senior Moderator
ERJ Open Res
. 2023 Oct 2;9(5):00249-2023.
doi: 10.1183/23120541.00249-2023. eCollection 2023 Sep. A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19: ACCORD-2
Tom Wilkinson[SUP] 1 [/SUP], Anthony De Soyza[SUP] 2 [/SUP], Miles Carroll[SUP] 3 [/SUP], James D Chalmers[SUP] 4 [/SUP], Michael G Crooks[SUP] 5 [/SUP], Gareth Griffiths[SUP] 6 7 [/SUP], Manu Shankar-Hari[SUP] 8 [/SUP], Ling-Pei Ho[SUP] 9 [/SUP], Alex Horsley[SUP] 10 [/SUP], Chris Kell[SUP] 11 [/SUP], Beatriz Lara[SUP] 12 [/SUP], Biswa Mishra[SUP] 13 [/SUP], Rachel Moate[SUP] 14 [/SUP], Clive Page[SUP] 15 [/SUP], Hitesh Pandya[SUP] 16 [/SUP], Jason Raw[SUP] 17 [/SUP], Fred Reid[SUP] 16 [/SUP], Dinesh Saralaya[SUP] 18 [/SUP], Ian C Scott[SUP] 19 [/SUP], Salman Siddiqui[SUP] 20 [/SUP], Andy Ustianowski[SUP] 21 [/SUP], Natalie van Zuydam[SUP] 22 [/SUP], Ashley Woodcock[SUP] 10 23 [/SUP], Dave Singh[SUP] 10 23 [/SUP]
Affiliations
Background: Increased serum interleukin (IL)-33 predicts poor outcomes in patients hospitalised with coronavirus disease 2019 (COVID-19). We examined the efficacy and safety of tozorakimab, a monoclonal antibody that neutralises IL-33, in improving outcomes in ACCORD-2 (EudraCT: 2020-001736-95).
Methods: ACCORD-2 was an open-label, phase 2a study in adults hospitalised with COVID-19. Patients were randomised 1:1 to tozorakimab 300 mg plus standard of care (SoC) or SoC alone. The primary end-point was time to clinical response (sustained clinical improvement of ≥2 points on the World Health Organization ordinal scale, discharge from hospital or fit for discharge) by day 29. Other end-points included death or respiratory failure, mortality and intensive care unit admission by day 29, and safety. Serum IL-33/soluble stimulated-2 (sST2) complex levels were measured by high-sensitivity immunoassay.
Results: Efficacy analyses included 97 patients (tozorakimab+SoC, n=53; SoC, n=44). Median time to clinical response did not differ between the tozorakimab and SoC arms (8.0 and 9.5 days, respectively; HR 0.96, 80% CI 0.70-1.31; one-sided p=0.33). Tozorakimab was well tolerated and the OR for risk of death or respiratory failure with treatment versus SoC was 0.55 (80% CI 0.27-1.12; p=0.26), while the OR was 0.31 (80% CI 0.09-1.06) in patents with high baseline serum IL-33/sST2 complex levels.
Conclusions: Overall, ACCORD-2 results suggest that tozorakimab could be a novel therapy for patients hospitalised with COVID-19, warranting further investigation in confirmatory phase 3 studies.
. 2023 Oct 2;9(5):00249-2023.
doi: 10.1183/23120541.00249-2023. eCollection 2023 Sep. A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19: ACCORD-2
Tom Wilkinson[SUP] 1 [/SUP], Anthony De Soyza[SUP] 2 [/SUP], Miles Carroll[SUP] 3 [/SUP], James D Chalmers[SUP] 4 [/SUP], Michael G Crooks[SUP] 5 [/SUP], Gareth Griffiths[SUP] 6 7 [/SUP], Manu Shankar-Hari[SUP] 8 [/SUP], Ling-Pei Ho[SUP] 9 [/SUP], Alex Horsley[SUP] 10 [/SUP], Chris Kell[SUP] 11 [/SUP], Beatriz Lara[SUP] 12 [/SUP], Biswa Mishra[SUP] 13 [/SUP], Rachel Moate[SUP] 14 [/SUP], Clive Page[SUP] 15 [/SUP], Hitesh Pandya[SUP] 16 [/SUP], Jason Raw[SUP] 17 [/SUP], Fred Reid[SUP] 16 [/SUP], Dinesh Saralaya[SUP] 18 [/SUP], Ian C Scott[SUP] 19 [/SUP], Salman Siddiqui[SUP] 20 [/SUP], Andy Ustianowski[SUP] 21 [/SUP], Natalie van Zuydam[SUP] 22 [/SUP], Ashley Woodcock[SUP] 10 23 [/SUP], Dave Singh[SUP] 10 23 [/SUP]
Affiliations
- PMID: 37868151
- PMCID: PMC10588785
- DOI: 10.1183/23120541.00249-2023
Background: Increased serum interleukin (IL)-33 predicts poor outcomes in patients hospitalised with coronavirus disease 2019 (COVID-19). We examined the efficacy and safety of tozorakimab, a monoclonal antibody that neutralises IL-33, in improving outcomes in ACCORD-2 (EudraCT: 2020-001736-95).
Methods: ACCORD-2 was an open-label, phase 2a study in adults hospitalised with COVID-19. Patients were randomised 1:1 to tozorakimab 300 mg plus standard of care (SoC) or SoC alone. The primary end-point was time to clinical response (sustained clinical improvement of ≥2 points on the World Health Organization ordinal scale, discharge from hospital or fit for discharge) by day 29. Other end-points included death or respiratory failure, mortality and intensive care unit admission by day 29, and safety. Serum IL-33/soluble stimulated-2 (sST2) complex levels were measured by high-sensitivity immunoassay.
Results: Efficacy analyses included 97 patients (tozorakimab+SoC, n=53; SoC, n=44). Median time to clinical response did not differ between the tozorakimab and SoC arms (8.0 and 9.5 days, respectively; HR 0.96, 80% CI 0.70-1.31; one-sided p=0.33). Tozorakimab was well tolerated and the OR for risk of death or respiratory failure with treatment versus SoC was 0.55 (80% CI 0.27-1.12; p=0.26), while the OR was 0.31 (80% CI 0.09-1.06) in patents with high baseline serum IL-33/sST2 complex levels.
Conclusions: Overall, ACCORD-2 results suggest that tozorakimab could be a novel therapy for patients hospitalised with COVID-19, warranting further investigation in confirmatory phase 3 studies.