tetano
Editor, Senior Moderator
J Infect Dis
. 2021 Jan 28;jiab036.
doi: 10.1093/infdis/jiab036. Online ahead of print.
Human Monoclonal Antibody Cocktail for the Treatment or Prophylaxis of Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV)
Sumathi Sivapalasingam[SUP] 1 [/SUP], George A Saviolakis[SUP] 2 [/SUP], Kirsten Kulcsar[SUP] 3 [/SUP], Aya Nakamura[SUP] 4 [/SUP], Thomas Conrad[SUP] 4 [/SUP], Mohamed Hassanein[SUP] 1 [/SUP], Giane Sumner[SUP] 1 [/SUP], Chinnasamy Elango[SUP] 1 [/SUP], Mohamed A Kamal[SUP] 1 [/SUP], Simon Eng[SUP] 1 [/SUP], Christos A Kyratsous[SUP] 1 [/SUP], Bret J Musser[SUP] 1 [/SUP], Matthew Frieman[SUP] 3 [/SUP], Joel Kantrowitz[SUP] 1 [/SUP], David M Weinreich[SUP] 1 [/SUP], George Yancopoulos[SUP] 1 [/SUP], Neil Stahl[SUP] 1 [/SUP], Leah Lipsich[SUP] 1 [/SUP]
Affiliations
Abstract
Background: REGN3048 and REGN3051 are human monoclonal antibodies (mAb) targeting the Spike (S) glycoprotein on the Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV), which binds to the receptor dipeptidyl peptidase-4 (DPP4) and is necessary for infection of susceptible cells.
Methods: Preclinical study: REGN3048, REGN3051 and isotype immunoglobulin G (IgG) were administered to huDPP4 mice 1 day prior to and 1 day after infection with MERS-CoV (Jordan strain). Virus titers and lung pathology were assessed. Phase 1 study: healthy adults received the combined mAb (n = 36) or placebo (n = 12) and followed for 121 days. Six dose levels were studied. Strict safety criteria were met prior to dose escalation.
Results: Preclinical study: REGN3048 plus REGN3051 prophylactically or therapeutically, is substantially more effective for reducing viral titer, lung inflammation and pathology in huDPP4 mice compared with control antibodies and to each antibody monotherapy. Phase 1 study: REGN3048 plus REGN3051 was well tolerated with no dose-limiting adverse events, deaths, serious adverse events, or infusion reactions. Each mAb displayed pharmacokinetics expected of human IgG1 antibodies; it was not immunogenic.
Conclusions: REGN3048 and REGN3051 in combination were well-tolerated. The clinical and preclinical data support further development for the treatment or prophylaxis of MERS-CoV infection.
Keywords: MERS; animal efficacy; first-in-human study; immunogenicity; monoclonal antibodies; pharmacokinetics; safety; tolerability.
. 2021 Jan 28;jiab036.
doi: 10.1093/infdis/jiab036. Online ahead of print.
Human Monoclonal Antibody Cocktail for the Treatment or Prophylaxis of Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV)
Sumathi Sivapalasingam[SUP] 1 [/SUP], George A Saviolakis[SUP] 2 [/SUP], Kirsten Kulcsar[SUP] 3 [/SUP], Aya Nakamura[SUP] 4 [/SUP], Thomas Conrad[SUP] 4 [/SUP], Mohamed Hassanein[SUP] 1 [/SUP], Giane Sumner[SUP] 1 [/SUP], Chinnasamy Elango[SUP] 1 [/SUP], Mohamed A Kamal[SUP] 1 [/SUP], Simon Eng[SUP] 1 [/SUP], Christos A Kyratsous[SUP] 1 [/SUP], Bret J Musser[SUP] 1 [/SUP], Matthew Frieman[SUP] 3 [/SUP], Joel Kantrowitz[SUP] 1 [/SUP], David M Weinreich[SUP] 1 [/SUP], George Yancopoulos[SUP] 1 [/SUP], Neil Stahl[SUP] 1 [/SUP], Leah Lipsich[SUP] 1 [/SUP]
Affiliations
- PMID: 33507266
- DOI: 10.1093/infdis/jiab036
Abstract
Background: REGN3048 and REGN3051 are human monoclonal antibodies (mAb) targeting the Spike (S) glycoprotein on the Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV), which binds to the receptor dipeptidyl peptidase-4 (DPP4) and is necessary for infection of susceptible cells.
Methods: Preclinical study: REGN3048, REGN3051 and isotype immunoglobulin G (IgG) were administered to huDPP4 mice 1 day prior to and 1 day after infection with MERS-CoV (Jordan strain). Virus titers and lung pathology were assessed. Phase 1 study: healthy adults received the combined mAb (n = 36) or placebo (n = 12) and followed for 121 days. Six dose levels were studied. Strict safety criteria were met prior to dose escalation.
Results: Preclinical study: REGN3048 plus REGN3051 prophylactically or therapeutically, is substantially more effective for reducing viral titer, lung inflammation and pathology in huDPP4 mice compared with control antibodies and to each antibody monotherapy. Phase 1 study: REGN3048 plus REGN3051 was well tolerated with no dose-limiting adverse events, deaths, serious adverse events, or infusion reactions. Each mAb displayed pharmacokinetics expected of human IgG1 antibodies; it was not immunogenic.
Conclusions: REGN3048 and REGN3051 in combination were well-tolerated. The clinical and preclinical data support further development for the treatment or prophylaxis of MERS-CoV infection.
Keywords: MERS; animal efficacy; first-in-human study; immunogenicity; monoclonal antibodies; pharmacokinetics; safety; tolerability.