tetano
Editor, Senior Moderator
Clin Transl Sci
. 2023 Oct 23.
doi: 10.1111/cts.13658. Online ahead of print. Enpatoran in COVID-19 pneumonia: Safety and efficacy results from a phase II randomized trial
John E McKinnon[SUP] 1 [/SUP], Joel Santiaguel[SUP] 2 [/SUP], Claudia Murta de Oliveira[SUP] 3 [/SUP], Dongzi Yu[SUP] 4 [/SUP], Mukhy Khursheed[SUP] 5 [/SUP], Flavie Moreau[SUP] 6 [/SUP], Lena Klopp-Schulze[SUP] 7 [/SUP], Jamie Shaw[SUP] 8 [/SUP], Sanjeev Roy[SUP] 9 [/SUP], Amy H Kao[SUP] 10 [/SUP]; ANEMONE Study Team
Collaborators, Affiliations
Enpatoran is a selective inhibitor of toll-like receptors 7 and 8 (TLR7/8) that potentially targets pro-inflammatory pathways induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A phase II study conducted in Brazil, the Philippines, and the USA during the early pandemic phase assessed the safety and efficacy of enpatoran in patients hospitalized with COVID-19 pneumonia (NCT04448756). A total of 149 patients, who scored 4 on the World Health Organization's (WHO) 9-point ordinal severity scale, were randomized 1:1:1 and received enpatoran 50 mg (n = 54) or 100 mg (n = 46), or placebo (n = 49) twice daily (b.i.d.) for 14 days plus standard of care. The primary objectives were safety and time to recovery (WHO 9-point scale ≤3). Clinical deterioration (WHO 9-point scale ≥ 5) was a key secondary objective. Treatment-emergent adverse events (TEAEs) were comparable across groups (56.5%-63.0%). Treatment-related TEAEs were numerically higher with enpatoran 50 mg (14.8%) than 100 mg (10.9%) or placebo (8.2%). Serious TEAEs were numerically lower with enpatoran (50 mg 9.3%, 100 mg 2.2%) than placebo (18.4%). The primary efficacy objective was not met; median time to recovery was 3.4-3.9 days across groups, with placebo-treated patients recovering on average faster than anticipated. Clinical deterioration event-free rates up to Day 7 were 90.6%, 95.6%, and 81.6% with enpatoran 50 mg, 100 mg, and placebo, respectively. Enpatoran was well tolerated by patients acutely ill and hospitalized with COVID-19 pneumonia. Positive signals in some secondary end points suggested potential beneficial effects, supporting further evaluation of enpatoran in patients with hyperinflammation due to infection or autoimmunity.
. 2023 Oct 23.
doi: 10.1111/cts.13658. Online ahead of print. Enpatoran in COVID-19 pneumonia: Safety and efficacy results from a phase II randomized trial
John E McKinnon[SUP] 1 [/SUP], Joel Santiaguel[SUP] 2 [/SUP], Claudia Murta de Oliveira[SUP] 3 [/SUP], Dongzi Yu[SUP] 4 [/SUP], Mukhy Khursheed[SUP] 5 [/SUP], Flavie Moreau[SUP] 6 [/SUP], Lena Klopp-Schulze[SUP] 7 [/SUP], Jamie Shaw[SUP] 8 [/SUP], Sanjeev Roy[SUP] 9 [/SUP], Amy H Kao[SUP] 10 [/SUP]; ANEMONE Study Team
Collaborators, Affiliations
- PMID: 37873555
- DOI: 10.1111/cts.13658
Enpatoran is a selective inhibitor of toll-like receptors 7 and 8 (TLR7/8) that potentially targets pro-inflammatory pathways induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A phase II study conducted in Brazil, the Philippines, and the USA during the early pandemic phase assessed the safety and efficacy of enpatoran in patients hospitalized with COVID-19 pneumonia (NCT04448756). A total of 149 patients, who scored 4 on the World Health Organization's (WHO) 9-point ordinal severity scale, were randomized 1:1:1 and received enpatoran 50 mg (n = 54) or 100 mg (n = 46), or placebo (n = 49) twice daily (b.i.d.) for 14 days plus standard of care. The primary objectives were safety and time to recovery (WHO 9-point scale ≤3). Clinical deterioration (WHO 9-point scale ≥ 5) was a key secondary objective. Treatment-emergent adverse events (TEAEs) were comparable across groups (56.5%-63.0%). Treatment-related TEAEs were numerically higher with enpatoran 50 mg (14.8%) than 100 mg (10.9%) or placebo (8.2%). Serious TEAEs were numerically lower with enpatoran (50 mg 9.3%, 100 mg 2.2%) than placebo (18.4%). The primary efficacy objective was not met; median time to recovery was 3.4-3.9 days across groups, with placebo-treated patients recovering on average faster than anticipated. Clinical deterioration event-free rates up to Day 7 were 90.6%, 95.6%, and 81.6% with enpatoran 50 mg, 100 mg, and placebo, respectively. Enpatoran was well tolerated by patients acutely ill and hospitalized with COVID-19 pneumonia. Positive signals in some secondary end points suggested potential beneficial effects, supporting further evaluation of enpatoran in patients with hyperinflammation due to infection or autoimmunity.