Pub Date : 2026-02-12Epub Date: 2025-11-06DOI: 10.1056/NEJMoa2510198
Richard Lafayette, Sean J Barbour, Robert M Brenner, Kirk N Campbell, Tom Doan, Necmi Eren, Jürgen Floege, Vivekanand Jha, Beom Seok Kim, Adrian Liew, Bart Maes, Atanu Pal, Roberto Pecoits-Filho, Richard K S Phoon, Dana V Rizk, Hitoshi Suzuki, Vladimir Tesař, Hernán Trimarchi, Xuelian Wei, Hong Zhang, Jonathan Barratt
Background: IgA nephropathy, the most common primary glomerulopathy worldwide, is a kidney disorder of B-cell origin characterized by mesangial accumulation of IgA-containing immune complexes. In at least 50% of patients, IgA nephropathy leads to kidney failure or death within 10 to 20 years after diagnosis. Atacicept is a native human transmembrane activator and calcium-modulator and cyclophilin-ligand interactor (TACI)-Fc fusion protein that inhibits two key immunoregulatory cytokines - B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) - that are thought to be central to the pathophysiology of IgA nephropathy.
Methods: In this ongoing, phase 3, multicenter, double-blind, randomized, placebo-controlled trial, we assigned patients with IgA nephropathy in a 1:1 ratio to receive atacicept at a dose of 150 mg once weekly, administered subcutaneously by patients at home, or matching placebo. The primary end point was the percentage change from baseline in the 24-hour urinary protein-to-creatinine ratio at week 36. Safety was also evaluated.
Results: A total of 203 patients were included in the prespecified interim analysis: 106 patients in the atacicept group and 97 in the placebo group. At week 36, the percentage reduction from baseline in the urinary protein-to-creatinine ratio was 45.7% in the atacicept group and 6.8% in the placebo group, with a geometric mean between-group difference of 41.8 percentage points (95% confidence interval, 28.9 to 52.3; P<0.001). Adverse events were observed in 59.3% of the patients in the atacicept group and in 50.0% in the placebo group; most were mild or moderate in severity.
Conclusions: In this prespecified interim analysis, treatment with atacicept resulted in a significantly greater reduction in proteinuria than placebo at week 36 in patients with IgA nephropathy. (Funded by Vera Therapeutics; ORIGIN 3 ClinicalTrials.gov number, NCT04716231.).
{"title":"A Phase 3 Trial of Atacicept in Patients with IgA Nephropathy.","authors":"Richard Lafayette, Sean J Barbour, Robert M Brenner, Kirk N Campbell, Tom Doan, Necmi Eren, Jürgen Floege, Vivekanand Jha, Beom Seok Kim, Adrian Liew, Bart Maes, Atanu Pal, Roberto Pecoits-Filho, Richard K S Phoon, Dana V Rizk, Hitoshi Suzuki, Vladimir Tesař, Hernán Trimarchi, Xuelian Wei, Hong Zhang, Jonathan Barratt","doi":"10.1056/NEJMoa2510198","DOIUrl":"10.1056/NEJMoa2510198","url":null,"abstract":"<p><strong>Background: </strong>IgA nephropathy, the most common primary glomerulopathy worldwide, is a kidney disorder of B-cell origin characterized by mesangial accumulation of IgA-containing immune complexes. In at least 50% of patients, IgA nephropathy leads to kidney failure or death within 10 to 20 years after diagnosis. Atacicept is a native human transmembrane activator and calcium-modulator and cyclophilin-ligand interactor (TACI)-Fc fusion protein that inhibits two key immunoregulatory cytokines - B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) - that are thought to be central to the pathophysiology of IgA nephropathy.</p><p><strong>Methods: </strong>In this ongoing, phase 3, multicenter, double-blind, randomized, placebo-controlled trial, we assigned patients with IgA nephropathy in a 1:1 ratio to receive atacicept at a dose of 150 mg once weekly, administered subcutaneously by patients at home, or matching placebo. The primary end point was the percentage change from baseline in the 24-hour urinary protein-to-creatinine ratio at week 36. Safety was also evaluated.</p><p><strong>Results: </strong>A total of 203 patients were included in the prespecified interim analysis: 106 patients in the atacicept group and 97 in the placebo group. At week 36, the percentage reduction from baseline in the urinary protein-to-creatinine ratio was 45.7% in the atacicept group and 6.8% in the placebo group, with a geometric mean between-group difference of 41.8 percentage points (95% confidence interval, 28.9 to 52.3; P<0.001). Adverse events were observed in 59.3% of the patients in the atacicept group and in 50.0% in the placebo group; most were mild or moderate in severity.</p><p><strong>Conclusions: </strong>In this prespecified interim analysis, treatment with atacicept resulted in a significantly greater reduction in proteinuria than placebo at week 36 in patients with IgA nephropathy. (Funded by Vera Therapeutics; ORIGIN 3 ClinicalTrials.gov number, NCT04716231.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"647-657"},"PeriodicalIF":78.5,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145454040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Paget's Disease of the Breast.","authors":"","doi":"10.1056/NEJMx260001","DOIUrl":"https://doi.org/10.1056/NEJMx260001","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"394 7","pages":"728"},"PeriodicalIF":78.5,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146168001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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{"title":"Targeting the Pathogenesis of IgA Nephropathy - A New Treatment Approach?","authors":"Marcello Tonelli","doi":"10.1056/NEJMe2518418","DOIUrl":"https://doi.org/10.1056/NEJMe2518418","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"394 7","pages":"712-713"},"PeriodicalIF":78.5,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146168039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-12Epub Date: 2026-02-07DOI: 10.1056/NEJMp2511798
John D Halamka, Micky Tripathi
{"title":"The Next Chapter in Health Care Interoperability.","authors":"John D Halamka, Micky Tripathi","doi":"10.1056/NEJMp2511798","DOIUrl":"https://doi.org/10.1056/NEJMp2511798","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"394 7","pages":"628-630"},"PeriodicalIF":78.5,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146214984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-12Epub Date: 2026-02-07DOI: 10.1056/NEJMp2515454
Heather Howard, Carmel Shachar
{"title":"The Rural Health Transformation Program - An Avenue for Promoting Administrative Policies.","authors":"Heather Howard, Carmel Shachar","doi":"10.1056/NEJMp2515454","DOIUrl":"https://doi.org/10.1056/NEJMp2515454","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"394 7","pages":"625-627"},"PeriodicalIF":78.5,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hooman A Azad, Dana Goin, Lisa M Nathan, Dena Goffman, Sonali Rajan, Uma Reddy, Mary E D'Alton, Danielle Laraque-Arena
{"title":"Overdose, Homicide, and Suicide as Causes of Maternal Death in the United States.","authors":"Hooman A Azad, Dana Goin, Lisa M Nathan, Dena Goffman, Sonali Rajan, Uma Reddy, Mary E D'Alton, Danielle Laraque-Arena","doi":"10.1056/NEJMc2512078","DOIUrl":"https://doi.org/10.1056/NEJMc2512078","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"394 7","pages":"722-723"},"PeriodicalIF":78.5,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146167966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Paul K Fadakar, Ali Pourvaziri, Adam S Feldman, Danielle B Pier, Thomas Denize
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