//Special note//---
Today, I have had a plan to share the contents
of the other article. However, the important articles which needs to urgently
communalize are published from Nature medicine and The New England Journal of
Medicine. Therefore, I change the original plan. I introduce a part of contents
about SARS-CoV-2 important reports exclusively today.
//Background//---
Aside from ongoing global vaccination,
treatment development for SARS-CoV-2 is prerequisite. To date, various
treatment options have been explored including the previous standard
treatment(2-4), convalescent plasma(5) and immunomodulators(4,6,7). In the
treatment options, passive humoral immunotherapy by intravenous infusion of
monoclonal antibody immediate to infection is effective to prevent SARS-CoV-2
symptom ingravescence(8). Two such neutralizing monoclonal antibodies,
bamlanivimab and etesevimab were isolated from convalescent plasma obtained
from patients with SARS-CoV-2 in the United States and China,
respectively(9,10).
---
(About antibodies)
*Bamlanivimab: Developed by Eli Lilly after
discovery by researches at AbCellera Biologics and at the Vaccine Research
Center of the National Institute of Allergy and Infectious Diseases.
*Etesevimab: Developed by the collaborative
efforts of Eli Lilly Junshi Biosciences, and the Institute of Microbiology of
the Chinese Academy of Sciences
---
(History, path)
*The FDA granted emergency use
authorization status for bamlanivimab plus etesevimab, administered together in
February 2021(11).
*The phase 2 and early portion of the phase
3 by BLAZE-1(#) shows efficacy against Covid-19-related hospitalization and
progression to severe disease.
(#)BLAZE-1: Blocking Viral Attachment and
Cell Entry with SARS-CoV-2 Neutralizing Antibodies
---
(The main clinical reports in this
Letter(1))
M.
Dougan, A. Nirula, M. Azizad et al report the findings from the latest portion
of the phase 3 BLAZE-1 trials for the adolescent(≧12
years) and adult patients with mild or moderate symptom who has high risk
factor for severe progression and received bamlanivimab plus etesevimab or
placebo in a comparative fashion.
//Condition(1)//---
*Place: The United States of America
*Period: 4/September/2020 to
8/December/2020 -- Enrolled time point.
*Participant: 1035
*Mean age: 53.8 years old.
*Drug Administration:
(2800 mg of bamlanivimab and 2800 mg of
etesevimab, administered together)
(Over a period of 1 hour)
*Participant condition: Outpatient setting
(mild or moderate symptom)
*Enrolling Timing: Within 3 days after
PCR-positive
*Risk factor(#): At least one → Enrolling
(#): An age ≥65
years; a body-mass index ≥35; chronic kidney disease, type 1 or type 2
diabetes, an immunocompromised condition, cardiovascular disease, hypertension,
and chronic respiratory disease; and receipt of immunosuppressive treatment
//Result(1)//---
By day 29
(The bamlanivimab-etesevimab group)
SARS-CoV-2 related hospitalization: 11 of
518 (2.1%) no death
(The placebo group)
SARS-CoV-2 related hospitalization: 36 of
517 (7.0%) 9 death
By day 7
Difference of Viral road reduction (Log)
-1.20 (CI:95%)
(Bamlanivimab-etesevimab group) / (placebo)
---
(Adverse Events)
Two group is almost same, but the adverse
event associated with immune response is slightly higher in monoclonal antibody
therapy groups.
//Discussion//---
*The viral road is significantly and rapid
reduced by 10^-4 (vs 10^-2.5 placebo), so symptom progression from 7 days to 10
days can be significantly prevented in monoclonal antibody therapy group. This
difference directly leads to clinical positive effect. In this clinical trial,
the patients were medically intervened in early phase immediate to infection.
Therefore, we need to adopt this therapy immediate after we confirm the symptom
in the case with any risk factor in order to replicate BLAZE-1 clinical study.
---
(Important note)
In
this trials, the B.1.351 lineage or P.1 lineage have been confirmed in only
less 5% of patients from viral sample(1). These lineages or the lineage with
escape mutant are dominant in the society. Monoclonal antibody efficacy
decreases in the lineage with escape mutants. Therefore, we need to modify
infused monoclonal antibody.
However, this clinical study shows efficacy of
early patient stratification in line with the risk factor and early efficient
anti-viral treatment. Therefore, we can utilize this medical protocol for
developing efficient anti-viral drugs.
//Support//---
Supported by Eli Lilly.
//Acknowledgment//---
We thank Lynn Naughton, Ph.D., of Eli
Lilly, for providing medical-writing and editorial support with an earlier
version of the manuscript.
(Reference)
(1)
Michael Dougan, M.D., Ph.D., Ajay Nirula,
M.D., Ph.D., Masoud Azizad, M.D., Bharat Mocherla, M.D., Robert L. Gottlieb,
M.D., Ph.D., Peter Chen, M.D., Corey Hebert, M.D., Russell Perry, M.D., Joseph
Boscia, M.D., Barry Heller, M.D., Jason Morris, M.D., Chad Crystal, M.D., Awawu
Igbinadolor, M.D., Gregory Huhn, M.D., M.P.H.T.M., Jose Cardona, M.D., Imad
Shawa, M.D., Princy Kumar, M.D., Andrew C. Adams, Ph.D., Jacob Van Naarden,
B.S., Kenneth L. Custer, Ph.D., M.B.A., Michael Durante, M.S., Gerard Oakley,
M.D., Andrew E. Schade, M.D., Ph.D., Timothy R. Holzer, Ph.D., Philip J. Ebert,
Ph.D., Richard E. Higgs, M.S., Nicole L. Kallewaard, Ph.D., Janelle Sabo,
Pharm.D., Dipak R. Patel, M.D., Ph.D., Matan C. Dabora, M.D., M.B.A., Paul
Klekotka, M.D., Ph.D., Lei Shen, Ph.D., and Daniel M. Skovronsky, M.D., Ph.D.
for the BLAZE-1 Investigators*
Bamlanivimab plus Etesevimab in Mild or
Moderate Covid-19
The New England Journal of Medicine July
14, 2021
---
Drs. Dougan and Nirula contributed equally
to this article.
Author Affiliations
From Massachusetts General Hospital and
Harvard Medical School, Boston (M. Dougan); Eli Lilly (A.N., A.C.A., J.V.N.,
K.L.C., M. Durante, G.O., A.E.S., T.R.H., P.J.E., R.E.H., N.L.K., J.S., D.R.P.,
M.C.D., P. Klekotka, L.S., D.M.S.), and Franciscan Health (I.S.) — both in
Indianapolis; Valley Clinical Trials–Northridge, Northridge (M.A.), the
Department of Medicine, Women’s Guild Lung Institute, Cedars–Sinai Medical
Center, Los Angeles (P.C.), and Long Beach Clinical Trials, Long Beach (B.H.) —
all in California; the Las Vegas Medical Research Center, Las Vegas (B.M.); Baylor
University Medical Center and Baylor Scott and White Research Institute, Dallas
(R.L.G.), and Gadolin Research, Beaumont (R.P.) — both in Texas; NOLA Research
Works, New Orleans (C.H.), and Clinical Trials of Southwest Louisiana, Lake
Charles (J.M.) — both in Louisiana; Vitalink Research, Union, SC (J.B.);
Eastside Research Associates, Redmond, WA (C.C.); Monroe Biomedical Research,
Monroe, NC (A.I.); Cook County Health, Chicago (G.H.); Indago Research and
Health Center, Hialeah, FL (J.C.); and Georgetown University, Washington, DC
(P. Kumar).
(2)
Cavalcanti AB, Zampieri FG, Rosa RG, et al.
Hydroxychloroquine with or without Azithromycin
in mild-to-moderate Covid-19.
N Engl J Med 2020; 383: 2041-52.
(3)
Beigel JH, Tomashek KM, Dodd LE, et al.
Remdesivir for the treatment of Covid-19 —
final report.
N Engl J Med 2020; 383: 1813-26.
(4)
The RECOVERY Collaborative Group.
Dexamethasone in
hospitalized patients with Covid-19.
N
Engl J Med
2021; 384: 693-704.
(5)
Joyner MJ, Senefeld JW, Klassen SA, et al.
Effect of convalescent plasma on
mortality among hospitalized
patients with COVID-19: initial
three-month experience.
August
12, 2020 (https://www . medrxiv . org/ content/
10 . 1101/ 2020 . 08 . 12 .
20169359v1). preprint.
(6)
Salama C, Han J, Yau L, et al.
Tocilizumab
in patients hospitalized
with Covid-19 pneumonia.
N Engl J Med 2021; 384: 20-30.
(7)
Roche.
Roche provides an update on the phase III
COVACTA Trial of Actemra/RoActemra in hospitalised patients with severe
COVID-19 associated pneumonia.
July
29, 2020 (https://www . roche . com/ investors/
updates/ inv - update - 2020 - 07
- 29 . htm).
(8)
Marston
HD, Paules CI,
Fauci AS.
Monoclonal antibodies for emerging
infectious diseases — borrowing from history.
N Engl J Med 2018; 378: 1469-72.
(9)
Jones BE, Brown-Augsburger PL, Corbett KS,
et al.
LY-CoV555, a rapidly isolated potent
neutralizing antibody, provides protection in a non-human primate model of
SARS-CoV-2 infection.
October
1, 2020 (https://pubmed . ncbi .
nlm . nih . gov/ 33024963/ ). preprint.
(10)
Shi R, Shan C, Duan X, et al.
A human neutralizing antibody
targets the receptor-binding site
of SARS-CoV-2.
Nature 2020; 584: 120-4.
(11)
Coronavirus (COVID-19) Update: FDA
authorizes monoclonal antibodies
for treatment of COVID-19.
News release ofthe Food and Drug
Administration, Silver Spring, MD, February
9, 2021
(https://www . fda . gov/ news - events/ press - announcements/ coronavirus - covid - 19 - update - fda -
authorizes - monoclonal - antibodies - treatment - covid - 19 - 0).
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