The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into a global pandemic and become a serious public health and socioeconomic burden, and thus there is an urgent need for effective means of control. Antibodies already have good precedents of application in the prevention and treatment of sudden and virulent infectious diseases. Many new effective antiviral therapies with fewer side effects have emerged with the flourishing of human’s biomedicine, and neutralizing antibodies are a dazzling one among them.
What are neutralizing antibodies?
Neutralizing antibodies are antibodies produced by B lymphocytes when pathogenic microorganisms invade the body. When viruses, bacteria and other pathogenic microorganisms invade the body, it activates the body’s immune system and stimulates B lymphocytes to produce a variety of antibodies. However, only some of these antibodies can rapidly recognize the pathogenic microorganisms, bind to the antigens on their surfaces and prevent the pathogenic microorganisms from invading the cells by binding to the receptors on the surfaces of the target cells, thereby protecting the body from infection. This process is called neutralization, and the acting antibodies are called neutralizing antibodies.
Antiviral mechanism of SARS-CoV-2 neutralizing antibodies
The COVID-19 pathogen SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2) on human cells via the spike protein (S protein) and undergoes a cell membrane infusion process, thereby allowing the virus to enter the cells to replicate through endocytosis and process and infect the body.
For SARS-CoV-2, the blocking neutralizing antibody in the RBD (receptor-binding region) of S protein can prevent the RBD of S protein from binding to ACE2, thereby preventing the virus from invading the host cells and ultimately preventing viral infection. This is an important way for neutralizing antibodies to exert their antiviral effects.
R&D progress of anti-SARS-CoV-2 neutralizing antibodies
Etesevimab（JS016/LY-CoV016）/ Bamlanivimab（LY-CoV555）
Junshi Biosciences announced on Jan. 27, 2021 that the double-antibody therapy of its neutralizing antibody etesevimab, developed in collaboration with Eli Lilly, and Eli Lilly’s bamlanivimab met the primary endpoint in the Phase 3 BLAZE-1 clinical trial, which significantly reduced hospitalizations and deaths in high-risk patients diagnosed with COVID-19. Many other healthcare supply companies also made contributions to helping those patients.
BLAZE-1 (NCT04427501) that met the primary endpoint is a randomized, double-blind, placebo-controlled Phase 2/3 study designed to assess the efficacy and safety of bamlanivimab alone or bamlanivimab and etesevimab together for the treatment of symptomatic COVID-19 in the outpatient setting. To be eligible, patients were required to have mild or moderate symptoms of COVID-19 as well as a positive SARS-CoV-2 test based on a sample collected no more than three days prior to drug infusion.
The primary endpoint measure for the Phase 3 portion of the BLAZE-1 trial was the percentage of participants who experience COVID-related hospitalizations or death from any cause by day 29. The key secondary endpoints were change from baseline to day 7 in SARS-CoV-2 viral load, persistently high SARS-CoV2 viral load on day 7, time to sustained symptom resolution, and COVID-related hospitalization, emergency room visit or death from any cause from baseline by day 29.
According to the results, across 1,035 patients, there were 11 events (2.1 percent) in patients taking the double-antibody therapy and 36 events (7.0 percent) in patients taking placebo, representing a 70 percent risk reduction (p= 0.0004). The double-antibody treatment group also demonstrated statistically significant improvements on all key secondary endpoints, providing strong evidence that the therapy reduced viral load and accelerated symptom resolution. The safety profile was consistent with observations from other Phase 1, Phase 2 and Phase 3 trials. Serious adverse events were reported at a similar frequency with the placebo group.
The FDA issued an emergency use authorization (EUA) on Nov. 10, 2020 for bamlanivimab for the treatment of mil...
(All Rights Reserved)