Dual 100% Efficacy Achieved: Neutralizing Antibody Therapies Break Through in Both Treatment and Prevention of COVID-19

In the development of therapies to combat the COVID-19 pandemic, the development of neutralizing antibodies has remained a key focus of research and development. By binding to the spike protein of SARS-CoV-2, neutralizing antibodies can prevent the virus from infecting cells. They can be used not only to treat patients infected with SARS-CoV-2 but also as a prophylactic therapy, providing passive immunity to high-risk populations susceptible to infection. Compared with vaccines, their advantage lies in their immediate efficacy following administration, and they remain effective in individuals who may not mount an adequate immune response to vaccination, including certain elderly individuals and immunocompromised patients.

Today, Eli Lilly and Company and Regeneron separately announced that their respective antibody combination therapies achieved 100% efficacy in preventing patient deaths and in preventing symptomatic COVID-19, respectively.

70% Reduction in Risk of Hospitalization/Death: Antibody Combination Therapy Meets Phase 3 Clinical Endpoints

Today, Eli Lilly and Company announced that the antibody combination therapy consisting of the neutralizing antibodies bamlanivimab (LY-CoV555) and etesevimab (LY-CoV016) met its primary endpoint in the Phase 3 BLAZE-1 clinical trial. Compared with the placebo group, the treatment group significantly reduced COVID-19-related hospitalizations and deaths among patients.

Bamlanivimab is a neutralizing antibody jointly developed by Eli Lilly and AbCellera, which has been granted Emergency Use Authorization (EUA) by the U.S. FDA for the treatment of mild to moderate COVID-19 in high-risk patients. Phase 3 clinical trial results released by Eli Lilly last week demonstrated that, as a prophylactic therapy, it reduced the risk of disease by 80% among elderly residents of nursing homes.

Etesevimab (LY-CoV016, also known as JS016) was initially co-developed by Junshi Biosciences and the Institute of Microbiology, Chinese Academy of Sciences. Last year, Eli Lilly obtained licensing rights from Junshi Biosciences to lead the clinical development globally outside the Greater China region. Both antibodies target the receptor-binding domain (RBD) of the spike protein but bind to different epitopes within the RBD; therefore, the combination therapy may yield superior therapeutic efficacy.

In the Phase 3 BLAZE-1 clinical trial, a total of 1,035 high-risk COVID-19 patients received either a neutralizing antibody combination therapy or placebo in addition to standard care. The trial results showed that 11 patients (2.1%) in the neutralizing antibody combination therapy group experienced hospitalization or death, compared with 36 patients (7.0%) in the control group, indicating that the antibody combination therapy reduced the risk of hospitalization and death by 70% (p=0.0004).

Regarding patient mortality data, the difference between the two groups was more pronounced. A total of 10 patient deaths occurred in the study, all of which were in the placebo group; there were no deaths in the antibody combination therapy group.

Furthermore, the neutralizing antibody combination also met multiple secondary endpoints in the clinical trial. For example, it significantly reduced viral load in patients at various time points after treatment compared with placebo.

Eli Lilly and Company stated that it has submitted an Emergency Use Authorization (EUA) application to the U.S. FDA for the use of this combination therapy in treating mild to moderate COVID-19 in high-risk patients. In collaboration with Amgen, the company expects to produce 1 million doses of the bamlanivimab and etesevimab combination therapy by mid-year. To enhance the convenience of administering this therapy, the company has provided data to the U.S. FDA supporting a reduction in intravenous infusion time from 60 minutes to 16 minutes.

100% Efficacy in Preventing Symptomatic COVID-19; Positive Interim Results for Regeneron Antibody Combination Therapy

Regeneron Announces Positive Interim Results from Phase 3 Trial of REGEN-COV (casirivimab and imdevimab) for the Prevention of COVID-19Regeneron announced today that its neutralizing antibody combination therapy, REGEN-COV (casirivimab and imdevimab), achieved positive interim results in a Phase 3 clinical trial for the prevention of COVID-19. The trial evaluated the efficacy of REGEN-COV as a passive vaccine in preventing COVID-19 among individuals at heightened risk of infection due to household exposure to a person with COVID-19. The results demonstrated a reduction in infection rates within one week of administration, and the therapy showed 100% efficacy in preventing symptomatic COVID-19.

The interim analysis included approximately 400 evaluable participants who were randomly assigned to receive either REGEN-COV or placebo. The trial results showed:

As a passive vaccine, REGEN-COV demonstrated 100% efficacy in preventing symptomatic COVID-19. In the placebo group, 3.58% (8/223) of participants contracted COVID-19, whereas no cases were observed in the REGEN-COV group (0/186). When asymptomatic infections were included, REGEN-COV reduced the overall risk of infection by 50%.

All infected patients in the REGEN-COV group had asymptomatic infections, and their peak viral loads and duration of viral shedding were significantly lower than those in the control group. The mean peak viral load in infected patients in the placebo group was 100 times higher than that in the treatment group. The duration of infection in patients in the REGEN-COV group did not exceed one week, whereas approximately 40% of patients in the placebo group had infections lasting 3–4 weeks.

“Clinical data on REGEN-COV as a passive vaccine show that it not only reduces viral load and disease symptoms in infected patients, but may also lower the risk of viral transmission,” said Dr. George D. Yancopoulos, President and Chief Scientific Officer at Regeneron. “Although highly effective vaccines are now available, we continue to see tens of thousands of people becoming infected every day, potentially transmitting the virus to those closest to them. REGEN-COV may help break this chain of transmission by providing immediate passive immunity to individuals at elevated risk of infection.”

In addition to Eli Lilly and Regeneron, there are currently more than 15 neutralizing antibody development projects for SARS-CoV-2 in clinical trials. Among them, AstraZeneca’s long-acting neutralizing antibody AZD7442 and VIR-7831, jointly developed by Vir Biotechnology and GlaxoSmithKline (GSK), have both entered Phase III clinical trials. BRII-196/BRII-198, jointly developed by Brii Biosciences, Tsinghua University, and Shenzhen Third People’s Hospital, has recently been included in a Phase II/III clinical trial sponsored by the U.S. National Institute of Allergy and Infectious Diseases (NIAID).

We look forward to more neutralizing antibody therapies achieving positive outcomes in the treatment and prevention of COVID-19, thereby providing another powerful tool against the pandemic alongside COVID-19 vaccines.

Note: This article aims to introduce medical and health research and does not constitute a recommendation for treatment plans. For guidance on treatment options, please consult a licensed hospital.

References:

[1] New data show treatment with Lilly's neutralizing antibodies bamlanivimab (LY-CoV555) and etesevimab (LY-CoV016) together reduced risk of COVID-19 hospitalizations and death by 70 percent. Retrieved January 26, 2021, from https://investor.lilly.com/news-releases/news-release-details/new-data-show-treatment-lillys-neutralizing-antibodies

[2] REGENERON REPORTS POSITIVE INTERIM DATA WITH REGEN-COV™ ANTIBODY COCKTAIL USED AS PASSIVE VACCINE TO PREVENT COVID-19. Retrieved January 26, 2021, from https://investor.regeneron.com/news-releases/news-release-details/regeneron-reports-positive-interim-data-regen-covtm-antibody

[3] COVID-19 Long-Acting AntiBody (LAAB) combination AZD7442 rapidly advances into Phase III clinical trials. Retrieved January 26, 2021, from https://www.astrazeneca.com/media-centre/press-releases/2020/covid-19-long-acting-antibody-laab-combination-azd7442-rapidly-advances-into-phase-iii-clinical-trials.html

[4] Large clinical trial will test combination monoclonal antibody therapy for mild/moderate COVID-19. Retrieved January 26, 2021, from https://www.nih.gov/news-events/news-releases/large-clinical-trial-will-test-combination-monoclonal-antibody-therapy-mild-moderate-covid-19

[5] COVID-19 therapies and vaccines: Clinical. Retrieved January 26, 2021, from https://www.biocentury.com/clinical-vaccines-and-therapies

[6] Yang et al, (2020) COVID-19 Antibody Therapeutics Tracker: A Global Online Database of Antibody Therapeutics for the Prevention and Treatment of COVID-19, Antibody Therapeutics, tbaa020, https://doi.org/10.1093/abt/tbaa020

[7] SARS-CoV-2 Neutralizing Antibody Program Update. Retrieved January 26, 2021, from https://investor.lilly.com/static-files/081a5ef7-f5d6-4acc-b0d2-7ae4daf9e953

[8] Large clinical trial will test combination monoclonal antibody therapy for mild/moderate COVID-19. Retrieved January 26, 2021, from https://www.nih.gov/news-events/news-releases/large-clinical-trial-will-test-combination-monoclonal-antibody-therapy-mild-moderate-covid-19.

▽Follow [WuXi AppTecDe】WeChat Official Account