Enpatoran in COVID‐19 pneumonia: Safety and efficacy results from a phase II randomized trial
Abstract 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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-12-01
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| Series: | Clinical and Translational Science |
| Online Access: | https://doi.org/10.1111/cts.13658 |
| _version_ | 1797391751578648576 |
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| author | John E. McKinnon Joel Santiaguel Claudia Murta de Oliveira Dongzi Yu Mukhy Khursheed Flavie Moreau Lena Klopp‐Schulze Jamie Shaw Sanjeev Roy Amy H. Kao the ANEMONE Study Team |
| author_facet | John E. McKinnon Joel Santiaguel Claudia Murta de Oliveira Dongzi Yu Mukhy Khursheed Flavie Moreau Lena Klopp‐Schulze Jamie Shaw Sanjeev Roy Amy H. Kao the ANEMONE Study Team |
| author_sort | John E. McKinnon |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-08T23:37:13Z |
| format | Article |
| id | doaj.art-dac7d19bf3f140e78fae2fdc00bbf872 |
| institution | Directory Open Access Journal |
| issn | 1752-8054 1752-8062 |
| language | English |
| last_indexed | 2024-03-08T23:37:13Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Science |
| spelling | doaj.art-dac7d19bf3f140e78fae2fdc00bbf8722023-12-14T06:03:04ZengWileyClinical and Translational Science1752-80541752-80622023-12-0116122640265310.1111/cts.13658Enpatoran in COVID‐19 pneumonia: Safety and efficacy results from a phase II randomized trialJohn E. McKinnon0Joel Santiaguel1Claudia Murta de Oliveira2Dongzi Yu3Mukhy Khursheed4Flavie Moreau5Lena Klopp‐Schulze6Jamie Shaw7Sanjeev Roy8Amy H. Kao9the ANEMONE Study TeamDivision of Infectious Disease, Department of Medicine Medical University of South Carolina Charleston South Carolina USADivision of Pulmonary Medicine University of the Philippines Manila PhilippinesAmbulatório de Pesquisa Clínica, Santa Casa de Misericórdia Belo Horizonte BrazilGlobal Clinical Development, EMD Serono Billerica Massachusetts USAGlobal Patient Safety Merck Serono Ltd. Feltham, UK, an affiliate of Merck KGaA Darmstadt GermanyGlobal Biostatistics, EMD Serono Billerica Massachusetts USATranslational Medicine, the healthcare business of Merck KGaA Darmstadt GermanyTranslational Medicine, EMD Serono Billerica Massachusetts USAGlobal Clinical Development Ares Trading SA, Eysins, Switzerland, an affiliate of Merck KGaA Darmstadt GermanyResearch Unit – Neuroscience & Immunology EMD Serono Billerica Massachusetts USAAbstract 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.https://doi.org/10.1111/cts.13658 |
| spellingShingle | John E. McKinnon Joel Santiaguel Claudia Murta de Oliveira Dongzi Yu Mukhy Khursheed Flavie Moreau Lena Klopp‐Schulze Jamie Shaw Sanjeev Roy Amy H. Kao the ANEMONE Study Team Enpatoran in COVID‐19 pneumonia: Safety and efficacy results from a phase II randomized trial Clinical and Translational Science |
| title | Enpatoran in COVID‐19 pneumonia: Safety and efficacy results from a phase II randomized trial |
| title_full | Enpatoran in COVID‐19 pneumonia: Safety and efficacy results from a phase II randomized trial |
| title_fullStr | Enpatoran in COVID‐19 pneumonia: Safety and efficacy results from a phase II randomized trial |
| title_full_unstemmed | Enpatoran in COVID‐19 pneumonia: Safety and efficacy results from a phase II randomized trial |
| title_short | Enpatoran in COVID‐19 pneumonia: Safety and efficacy results from a phase II randomized trial |
| title_sort | enpatoran in covid 19 pneumonia safety and efficacy results from a phase ii randomized trial |
| url | https://doi.org/10.1111/cts.13658 |
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