New England Journal of Medicine

John P.H. Wilding, D.M., Rachel L. Batterham, M.B., B.S., Ph.D., Salvatore Calanna, Ph.D., Melanie Davies, M.D., Luc F. Van Gaal, M.D., Ph.D., Ildiko Lingvay, M.D., M.P.H., M.S.C.S., Barbara M. McGowan, M.D., Ph.D., Julio Rosenstock, M.D., Marie T.D. Tran, M.D., Ph.D., Thomas A. Wadden, Ph.D., Sean Wharton, M.D., Pharm.D., Koutaro Yokote, M.D., Ph.D., Niels Zeuthen, M.Sc., and Robert F. Kushner, M.D. for the STEP 1 Study Group*

doi : 10.1056/NEJMoa2032183

N Engl J Med 2021; 384:989-1002

Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed.

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Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition

Lawrence Corey, M.D., Peter B. Gilbert, Ph.D., Michal Juraska, Ph.D., David C. Montefiori, Ph.D., Lynn Morris, Ph.D., Shelly T. Karuna, M.D., Srilatha Edupuganti, M.D., Nyaradzo M. Mgodi, M.B., Ch.B., M.Med., Allan C. deCamp, Ph.D., Erika Rudnicki, M.S., Yunda Huang, Ph.D., Pedro Gonzales, M.D., Robinson Cabello, M.D., Catherine Orrell, M.B., Ch.B., Ph.D., Javier R. Lama, M.D., M.P.H., Fatima Laher, M.B., B.Ch., Erica M. Lazarus, M.B., Ch.B., Jorge Sanchez, M.D., M.P.H., Ian Frank, M.D., Juan Hinojosa, M.D., Magdalena E. Sobieszczyk, M.D., M.P.H., Kyle E. Marshall, M.S., Pamela G. Mukwekwerere, M.B., Ch.B., Joseph Makhema, M.B., Ch.B., Lindsey R. Baden, M.D., James I. Mullins, Ph.D., Carolyn Williamson, Ph.D., John Hural, Ph.D., M. Juliana McElrath, M.D., Ph.D., Carter Bentley, Ph.D., Simbarashe Takuva, M.B., Ch.B., Margarita M. Gomez Lorenzo, M.D., David N. Burns, M.D., Nicole Espy, Ph.D., April K. Randhawa, Ph.D., Nidhi Kochar, M.S., Estelle Piwowar-Manning, M.T., Deborah J. Donnell, Ph.D., Nirupama Sista, Ph.D., Philip Andrew, R.N., James G. Kublin, M.D., Glenda Gray, M.B., B.Ch., Julie E. Ledgerwood, D.O., John R. Mascola, M.D., and Myron S. Cohen, M.D. for the HVTN 704/HPTN 085 and HVTN 703/HPTN 081 Study Teams*

doi : 10.1056/NEJMoa2031738

N Engl J Med 2021; 384:1003-1014

Whether a broadly neutralizing antibody (bnAb) can be used to prevent human immunodeficiency virus type 1 (HIV-1) acquisition is unclear.

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Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19

Michael J. Joyner, M.D., Rickey E. Carter, Ph.D., Jonathon W. Senefeld, Ph.D., Stephen A. Klassen, Ph.D., John R. Mills, Ph.D., Patrick W. Johnson, B.S., Elitza S. Theel, Ph.D., Chad C. Wiggins, Ph.D., Katelyn A. Bruno, Ph.D., Allan M. Klompas, M.B., B.Ch., B.A.O., Elizabeth R. Lesser, M.S., Katie L. Kunze, Ph.D., Matthew A. Sexton, M.D., Juan C. Diaz Soto, M.D., Sarah E. Baker, Ph.D., John R.A. Shepherd, M.D., Noud van Helmond, M.D., Nicole C. Verdun, M.D., Peter Marks, M.D., Ph.D., Camille M. van Buskirk, M.D., Jeffrey L. Winters, M.D., James R. Stubbs, M.D., Robert F. Rea, M.D., David O. Hodge, M.S., Vitaly Herasevich, M.D., Ph.D., Emily R. Whelan, B.S., Andrew J. Clayburn, B.S., Kathryn F. Larson, M.D., Juan G. Ripoll, M.D., Kylie J. Andersen, B.S., Matthew R. Buras, M.S., Matthew N.P. Vogt, M.D., Joshua J. Dennis, B.S., Riley J. Regimbal, B.S., Philippe R. Bauer, M.D., Ph.D., Janis E. Blair, M.D., Nigel S. Paneth, M.D., M.P.H., DeLisa Fairweather, Ph.D., R. Scott Wright, M.D., and Arturo Casadevall, M.D., Ph.D.

doi : 10.1056/NEJMoa2031893

N Engl J Med 2021; 384:1015-1027

Convalescent plasma has been widely used to treat coronavirus disease 2019 (Covid-19) under the presumption that such plasma contains potentially therapeutic antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be passively transferred to the plasma recipient. Whether convalescent plasma with high antibody levels rather than low antibody levels is associated with a lower risk of death is unknown.

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Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria

Peter Hillmen, M.B., Ch.B., Ph.D., Jeff Szer, M.B., B.S., Ilene Weitz, M.D., Alexander R?th, M.D., Britta H?chsmann, M.D., Jens Panse, M.D., Kensuke Usuki, M.D., Ph.D., Morag Griffin, B.M.Sc., M.B., Ch.B., Jean-Jacques Kiladjian, M.D., Ph.D., Carlos de Castro, M.D., Hisakazu Nishimori, M.D., Ph.D., Lisa Tan, R.N., Mohamed Hamdani, M.S., Pascal Deschatelets, Ph.D., Cedric Francois, M.D., Ph.D., Federico Grossi, M.D., Ph.D., Temitayo Ajayi, M.D., Antonio Risitano, M.D., Ph.D., and Régis Peffault de la Tour, M.D., Ph.D.

doi : 10.1056/NEJMoa2029073

N Engl J Med 2021; 384:1028-1037

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disease characterized by chronic complement-mediated hemolysis. C5 inhibition controls intravascular hemolysis in untreated PNH but cannot address extravascular hemolysis. Pegcetacoplan, a pegylated peptide targeting proximal complement protein C3, potentially inhibits both intravascular and extravascular hemolysis.

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