Safety and efficacy of astegolimab for COPD with frequent exacerbations regardless of baseline blood eosinophil counts (ALIENTO and ARNASA): randomised, double-blind, placebo-controlled, phase 2b and 3 trials.
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| Title: | Safety and efficacy of astegolimab for COPD with frequent exacerbations regardless of baseline blood eosinophil counts (ALIENTO and ARNASA): randomised, double-blind, placebo-controlled, phase 2b and 3 trials. |
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| Authors: | Papi, Alberto (AUTHOR), Greening, Neil J (AUTHOR), Bhatt, Surya P (AUTHOR), Roche, Nicolas (AUTHOR), Celli, Bartolome (AUTHOR), Wedzicha, Jadwiga A (AUTHOR), Agustí, Àlvar (AUTHOR), Tal-Singer, Ruth (AUTHOR), Han, MeiLan K (AUTHOR), Janssens, Wim (AUTHOR), Hanania, Nicola A (AUTHOR), Nair, Parameswaran (AUTHOR), Bremner, Peter (AUTHOR), Porpodis, Konstantinos (AUTHOR), Shibata, Yoko (AUTHOR), Korn, Stephanie (AUTHOR), Yang, Ting (AUTHOR), Gordon, Oliver (AUTHOR), Saenz, Rebecca (AUTHOR), Ng, Julie (AUTHOR) |
| Source: | Lancet. May2026, Vol. 407 Issue 10543, p2027-2039. 13p. |
| Subjects: | Chronic obstructive pulmonary disease, Disease exacerbation, Monoclonal antibodies, Patient safety, Interleukin-33, Clinical trials |
| Abstract: | Interleukin-33 and its receptor, ST2, are implicated in neutrophilic and eosinophilic inflammation during chronic obstructive pulmonary disease (COPD) exacerbations. We aimed to assess the efficacy and safety of astegolimab, an anti-ST2 human IgG2 monoclonal antibody, which were evaluated in two COPD pivotal trials. In two randomised, double-blind, placebo-controlled trials (phase 2b ALIENTO and phase 3 ARNASA), current or former smokers with COPD and a history of frequent exacerbations, irrespective of baseline blood eosinophils, were randomly assigned (1:1:1; stratification by smoking status and region) to receive subcutaneous astegolimab 476 mg every 2 weeks, every 4 weeks, or placebo, alongside optimised inhaled maintenance therapy over 52 weeks. The primary endpoint (analysed in participants receiving one or more doses) was annualised rate of moderate or severe exacerbations. Missing data were considered similar to data from other participants in the same treatment group with the same baseline characteristics. The trials were registered with ClinicalTrials.gov (NCT05037929 and NCT05595642). In ALIENTO, 1301 participants (astegolimab every 2 weeks, n=433; astegolimab every 4 weeks, n=437; and placebo, n=431) initiated treatment between Oct 5, 2021, and Feb 19, 2024. In ARNASA, 1375 participants (astegolimab every 2 weeks, n=459; astegolimab every 4 weeks, n=459; and placebo, n=457) initiated treatment between Jan 9, 2023, and June 25, 2024. Adjusted rate ratios versus placebo for the primary endpoint were 0·85 (95% CI 0·72–1·00; p=0·049) for astegolimab every 2 weeks and 0·93 (0·79–1·10; p=0·38) for astegolimab every 4 weeks in ALIENTO, and 0·85 (0·72–1·01; p=0·068) for astegolimab every 2 weeks and 0·82 (0·70–0·98; p=0·024) for astegolimab every 4 weeks in ARNASA. Adverse events were balanced between treatments, with most participants experiencing one or more adverse events (1093 [84·0%] of 1301 participants in ALIENTO and 1176 [85·5%] of 1375 in ARNASA). The most common non-COPD adverse event was nasopharyngitis in ALIENTO and upper respiratory chest infection in ARNASA. Deaths occurred in 40 (3·1%) of 1301 participants in ALIENTO and in 44 (3·2%) of 1375 participants in ARNASA, and were balanced across treatment groups. Across both trials, a total of three deaths (0·1%) were considered to be related to treatment by investigators. In ALIENTO, astegolimab every 2 weeks was associated with a lower annual rate of exacerbations versus placebo in patients with COPD and a history of frequent exacerbations. In ARNASA, these findings did not meet statistical significance. Together, these findings suggest a role for targeting the ST2/IL-33 pathway to reduce the frequency of COPD exacerbations in patients with limited treatment options. Genentech, a member of the Roche Group, and F Hoffmann-La Roche. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Text: Availability: 0 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 193959016 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Safety and efficacy of astegolimab for COPD with frequent exacerbations regardless of baseline blood eosinophil counts (ALIENTO and ARNASA): randomised, double-blind, placebo-controlled, phase 2b and 3 trials. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Papi%2C+Alberto%22">Papi, Alberto</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Greening%2C+Neil+J%22">Greening, Neil J</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bhatt%2C+Surya+P%22">Bhatt, Surya P</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Roche%2C+Nicolas%22">Roche, Nicolas</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Celli%2C+Bartolome%22">Celli, Bartolome</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wedzicha%2C+Jadwiga+A%22">Wedzicha, Jadwiga A</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Agustí%2C+Àlvar%22">Agustí, Àlvar</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Tal-Singer%2C+Ruth%22">Tal-Singer, Ruth</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Han%2C+MeiLan+K%22">Han, MeiLan K</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Janssens%2C+Wim%22">Janssens, Wim</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hanania%2C+Nicola+A%22">Hanania, Nicola A</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Nair%2C+Parameswaran%22">Nair, Parameswaran</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bremner%2C+Peter%22">Bremner, Peter</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Porpodis%2C+Konstantinos%22">Porpodis, Konstantinos</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Shibata%2C+Yoko%22">Shibata, Yoko</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Korn%2C+Stephanie%22">Korn, Stephanie</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yang%2C+Ting%22">Yang, Ting</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gordon%2C+Oliver%22">Gordon, Oliver</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Saenz%2C+Rebecca%22">Saenz, Rebecca</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ng%2C+Julie%22">Ng, Julie</searchLink> (AUTHOR) – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Lancet%22">Lancet</searchLink>. May2026, Vol. 407 Issue 10543, p2027-2039. 13p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Chronic+obstructive+pulmonary+disease%22">Chronic obstructive pulmonary disease</searchLink><br /><searchLink fieldCode="DE" term="%22Disease+exacerbation%22">Disease exacerbation</searchLink><br /><searchLink fieldCode="DE" term="%22Monoclonal+antibodies%22">Monoclonal antibodies</searchLink><br /><searchLink fieldCode="DE" term="%22Patient+safety%22">Patient safety</searchLink><br /><searchLink fieldCode="DE" term="%22Interleukin-33%22">Interleukin-33</searchLink><br /><searchLink fieldCode="DE" term="%22Clinical+trials%22">Clinical trials</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Interleukin-33 and its receptor, ST2, are implicated in neutrophilic and eosinophilic inflammation during chronic obstructive pulmonary disease (COPD) exacerbations. We aimed to assess the efficacy and safety of astegolimab, an anti-ST2 human IgG2 monoclonal antibody, which were evaluated in two COPD pivotal trials. In two randomised, double-blind, placebo-controlled trials (phase 2b ALIENTO and phase 3 ARNASA), current or former smokers with COPD and a history of frequent exacerbations, irrespective of baseline blood eosinophils, were randomly assigned (1:1:1; stratification by smoking status and region) to receive subcutaneous astegolimab 476 mg every 2 weeks, every 4 weeks, or placebo, alongside optimised inhaled maintenance therapy over 52 weeks. The primary endpoint (analysed in participants receiving one or more doses) was annualised rate of moderate or severe exacerbations. Missing data were considered similar to data from other participants in the same treatment group with the same baseline characteristics. The trials were registered with ClinicalTrials.gov (NCT05037929 and NCT05595642). In ALIENTO, 1301 participants (astegolimab every 2 weeks, n=433; astegolimab every 4 weeks, n=437; and placebo, n=431) initiated treatment between Oct 5, 2021, and Feb 19, 2024. In ARNASA, 1375 participants (astegolimab every 2 weeks, n=459; astegolimab every 4 weeks, n=459; and placebo, n=457) initiated treatment between Jan 9, 2023, and June 25, 2024. Adjusted rate ratios versus placebo for the primary endpoint were 0·85 (95% CI 0·72–1·00; p=0·049) for astegolimab every 2 weeks and 0·93 (0·79–1·10; p=0·38) for astegolimab every 4 weeks in ALIENTO, and 0·85 (0·72–1·01; p=0·068) for astegolimab every 2 weeks and 0·82 (0·70–0·98; p=0·024) for astegolimab every 4 weeks in ARNASA. Adverse events were balanced between treatments, with most participants experiencing one or more adverse events (1093 [84·0%] of 1301 participants in ALIENTO and 1176 [85·5%] of 1375 in ARNASA). The most common non-COPD adverse event was nasopharyngitis in ALIENTO and upper respiratory chest infection in ARNASA. Deaths occurred in 40 (3·1%) of 1301 participants in ALIENTO and in 44 (3·2%) of 1375 participants in ARNASA, and were balanced across treatment groups. Across both trials, a total of three deaths (0·1%) were considered to be related to treatment by investigators. In ALIENTO, astegolimab every 2 weeks was associated with a lower annual rate of exacerbations versus placebo in patients with COPD and a history of frequent exacerbations. In ARNASA, these findings did not meet statistical significance. Together, these findings suggest a role for targeting the ST2/IL-33 pathway to reduce the frequency of COPD exacerbations in patients with limited treatment options. Genentech, a member of the Roche Group, and F Hoffmann-La Roche. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/S0140-6736(26)00637-9 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 13 StartPage: 2027 Subjects: – SubjectFull: Chronic obstructive pulmonary disease Type: general – SubjectFull: Disease exacerbation Type: general – SubjectFull: Monoclonal antibodies Type: general – SubjectFull: Patient safety Type: general – SubjectFull: Interleukin-33 Type: general – SubjectFull: Clinical trials Type: general Titles: – TitleFull: Safety and efficacy of astegolimab for COPD with frequent exacerbations regardless of baseline blood eosinophil counts (ALIENTO and ARNASA): randomised, double-blind, placebo-controlled, phase 2b and 3 trials. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Papi, Alberto – PersonEntity: Name: NameFull: Greening, Neil J – PersonEntity: Name: NameFull: Bhatt, Surya P – PersonEntity: Name: NameFull: Roche, Nicolas – PersonEntity: Name: NameFull: Celli, Bartolome – PersonEntity: Name: NameFull: Wedzicha, Jadwiga A – PersonEntity: Name: NameFull: Agustí, Àlvar – PersonEntity: Name: NameFull: Tal-Singer, Ruth – PersonEntity: Name: NameFull: Han, MeiLan K – PersonEntity: Name: NameFull: Janssens, Wim – PersonEntity: Name: NameFull: Hanania, Nicola A – PersonEntity: Name: NameFull: Nair, Parameswaran – PersonEntity: Name: NameFull: Bremner, Peter – PersonEntity: Name: NameFull: Porpodis, Konstantinos – PersonEntity: Name: NameFull: Shibata, Yoko – PersonEntity: Name: NameFull: Korn, Stephanie – PersonEntity: Name: NameFull: Yang, Ting – PersonEntity: Name: NameFull: Gordon, Oliver – PersonEntity: Name: NameFull: Saenz, Rebecca – PersonEntity: Name: NameFull: Ng, Julie IsPartOfRelationships: – BibEntity: Dates: – D: 23 M: 05 Text: May2026 Type: published Y: 2026 Identifiers: – Type: issn-print Value: 01406736 Numbering: – Type: volume Value: 407 – Type: issue Value: 10543 Titles: – TitleFull: Lancet Type: main |
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