amubarvimab (BRII-196) / Tsinghua University, Brii Biosci, Third Peoples Hospital of Shenzhen, Sinopharm - LARVOL DELTA

Implementation of a seamless phase 2/3 study design in the setting of an emergent infectious disease pandemic: Lessons learned from the ACTIV-2 platform COVID-19 treatment trial. (PubMed, Contemp Clin Trials) - "A seamless transition and approximately 20 % reduction in total sample size was achieved for one agent, amubarvimab plus romlusevimab. Using both simulation studies and actual results from graduation assessments of five ACTIV-2 candidate therapeutics, we provide a discussion of lessons learned from our implementation and recommendations for future seamless trials of interventions for emergent infections."

Journal • P2/3 data • Infectious Disease • Novel Coronavirus Disease

The effect of amubarvimab-romlusevimab on clinical outcomes in patients with COVID-19: a meta-analysis. (PubMed, J Infect) - No abstract available

Clinical data • Journal • Retrospective data • Infectious Disease • Novel Coronavirus Disease

Long-term outcomes of passive immunotherapy for COVID-19: A pooled analysis of a large multinational platform randomized clinical trial. (PubMed, Clin Microbiol Infect) - P3 | "In our large study of long half-life passive immunotherapy for hospitalized patients with COVID-19, we did not find evidence of a long-term effect on either mortality or rehospitalization."

Clinical • Journal • Retrospective data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Viral and symptom rebound following anti-SARS-CoV-2 monoclonal antibody therapy in a randomized placebo-controlled trial. (PubMed, J Infect Dis) - "We explored viral and symptom rebound after COVID-19 amubarvimab/romlusevimab monoclonal antibody therapy vs placebo in the randomized ACTIV-2/A5401 trial. Viral rebound was defined as RNA ≥3 and ≥0.5 log10 copies/mL increase from day 3 or 7, and symptom rebound as hospitalization or any moderate/severe symptom for ≥2 days after initial symptom improvement. There was no difference in viral rebound (∼5%/arm) (analysis population n=713) or symptom rebound among participants who initially improved (hazard ratio 0.95 (95% CI 0.52, 1.75, analysis population) n=574); <1% had both viral/symptom rebound."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Effect of amubarvimab-romlusevimab for treatment of severe COVID-19 in intensive care units: A retrospective cohort study. (PubMed, Heliyon) - "After including the above covariates, Multifactorial COX regression shows that the Amubarvimab - romlusevimab therapy(HR:0.392; CI:[0.211-0.729]; p:0.003), CRP, Lactate and PT-INR at admission are independent factors for mortality of severe COVID-19. Based on the current data, we conclude that amubarvimab-romlusevimab therapy is beneficial for patients with severe COVID-19."

Journal • Retrospective data • Cardiovascular • Critical care • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Post-acute COVID-19 outcomes including participant-reported long COVID: amubarvimab/romlusevimab versus placebo in the ACTIV-2 trial. (PubMed, EClinicalMedicine) - "National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences."

Clinical • Journal • Allergy • Immunology • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Sotrovimab in the treatment of coronavirus disease-2019 (COVID-19): a systematic review and meta-analysis of randomized clinical trials. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "The total population consisted of 5470 patients with COVID-19, 1921 (35%) in the sotrovimab group and 3549 (65%) in the control group (placebo or BRII-196 + BRII-198 or casirivimab + imdevimab or bamlanivimab + etesevimab, administered in a similar way to sotrovimab, in a single dose with a 60-min intravenous infusion)...The use of sotrovimab in the treatment of patients with COVID-19 had no significant impact on mortality and need for mechanical ventilation and did not appear to be safer compared to controls. However, there was evidence of effectiveness in reducing the rate of hospitalization, although the certainty of the evidence is moderate and the risk of bias is high."

Clinical • Journal • Retrospective data • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Early trajectories of virological and immunological biomarkers and clinical outcomes in patients admitted to hospital for COVID-19: an international, prospective cohort study. (PubMed, Lancet Microbe) - "Patients admitted to hospital with less favourable 5-day biomarker trajectories had worse prognosis, suggesting that persistent viral burden might drive inflammation in the pathogenesis of COVID-19, identifying patients that might benefit from escalation of antiviral or anti-inflammatory treatment."

Biomarker • Clinical data • Journal • Chronic Kidney Disease • Infectious Disease • Inflammation • Nephrology • Novel Coronavirus Disease • Renal Disease • Respiratory Diseases • CRP • IL6

Characterization of treatment resistance and viral kinetics in the setting of single- versus dual-active monoclonal antibodies against SARS-CoV-2. (PubMed, J Infect Dis) - "Compared to single-active mAb therapy, dual-active mAbs led to similar clinical outcomes, but significantly faster viral load decline and a lower risk of emergent resistance."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Treatment for Covid-19 with SARS-CoV-2 neutralizing antibody BRII-196(Ambavirumab) plus BRII-198(Lomisivir): a retrospective cohort study. (PubMed, BMC Pharmacol Toxicol) - "The neutralizing antibody therapy, BRII-196 plus BRII-198 could shorten LOS and interval of Covid-19 nucleic acid from positive to negative. However, it didn't show efficacy for improving clinical outcomes among severe or critical cases."

Journal • Retrospective data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Efficacy of the combination of BRII-196/BRII-198 in the treatment of COVID-19 vaccine breakthrough infections. (PubMed, Am J Transl Res) - "The initial levels of SARS-CoV-2 IgG antibody and lymphocytes in fully vaccinated patients with breakthrough infections are inversely correlated with the severity of the disease. Early treatment with BRII-196/BRII-198 can shorten NA negative conversion time in severe COVID-19 patients and increase in vivo neutralizing antibody levels post-conversion, providing lasting protection. However, BRII-196/BRII-198 does not influence lymphocyte count recovery in patients with either ordinary and/or severe COVID-19."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Viral and Symptom Rebound After COVID-19 Monoclonal Antibody Therapy in the ACTIV-2 Trial (CROI 2024) - "Background: Risk of viral and symptom rebound after monoclonal antibody (mAb) therapy for COVID-19 is unknown.Viral and symptom rebound in a randomized placebo-controlled trial of combination mAbs Amubarvimab/Romlusevimab (A/R), which had been shown to reduce hospitalization/death by 79%, were explored. This randomized trial found no significant differences in symptom experiences or viral rebound between mAb- vs placebo-treated participants. With or without treatment, rebound rates were low following sustained symptom improvement or resolution."

Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Impact of BA.1, BA.2, and BA.4/BA.5 Omicron mutations on therapeutic monoclonal antibodies. (PubMed, Comput Biol Med) - "We conducted a systematic molecular dynamics (MD) simulation to investigate how the RBD mutations of these subvariants affect the interactions with broad mAbs including AstraZeneca (COV2-2196 and COV2-2130), Brii Biosciences (BRII-196), Celltrion (CT-P59), Eli Lilly (LY-CoV555 and LY-CoV016), Regeneron (REGN10933 and REGN10987), Vir Biotechnology (S309), and S2X259. We introduce a mutational escape map for each mAb to identify the key RBD sites and the corresponding critical mutations. Overall, our findings suggest that the majority of therapeutic mAbs have diminished or missing activity against Omicron subvariants, indicating the urgent need for a new therapeutic mAb with a better design."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

TICO: ACTIV-3: Therapeutics for Inpatients With COVID-19 (clinicaltrials.gov) - P3 | N=2753 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease

ACTIV-2: A Study for Outpatients With COVID-19 (clinicaltrials.gov) - P2/3 | N=4044 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease

Potent antibodies against immune invasive SARS-CoV-2 Omicron subvariants. (PubMed, Int J Biol Macromol) - "Most nAbs (COV2-2130, ZCB11, REGN10933) or combinations of nAbs (COV2-2196 + COV2-2130, REGN10933 + REGN10987, Brii-196 + Brii-198) have either greatly reduced or lost their neutralizing ability against Omicron, but several nAbs such as SA55, SA58, S309, LY-CoV1404 are still effective in neutralizing most Omicron subvariants. This paper focuses on Omicron subvariants mutations and mechanisms of current therapeutic antibodies that remain efficacious against Omicron subvariants, which will guide us in exploring a new generation of broad nAbs as key therapeutics to tackle SARS-CoV-2 and accelerate the exploration of novel clinical antiviral reagents."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Effect of the Timing of Amubarvimab/Romlusevimab (BRII-196/198) Administration on Progression to Severe Disease in Elderly Patients with COVID-19 Infection: A Retrospective Cohort Study. (PubMed, Intensive Care Res) - "The multivariate Cox regression analysis revealed low flow oxygen support prior to BRII-196/198 administration (HR 3.53, 95% CI 1.42-8.77, P < 0.01) and PLT class (HR 3.68, 95% CI 1.37-9.91, P < 0.01) as independent predictors of disease progression. In elderly patients with mild or moderate COVID-19 disease, who do not require oxygen support and had the risk factors for disease progression to severe COVID-19 disease, the administration of BRII-196/198 within 3 days resulted in a beneficial trend in terms of preventing disease progression."

Journal • Retrospective data • Geriatric Disorders • Infectious Disease • Novel Coronavirus Disease

Safety and Efficacy of Combination SARS-CoV-2 Neutralizing Monoclonal Antibodies Amubarvimab Plus Romlusevimab in Nonhospitalized Patients With COVID-19. (PubMed, Ann Intern Med) - P2/3 | "Amubarvimab plus romlusevimab was safe and significantly reduced the risk for hospitalization and/or death among nonhospitalized adults with mild to moderate SARS-CoV-2 infection at high risk for progression to severe disease. National Institute of Allergy and Infectious Diseases of the National Institutes of Health."

Journal • Allergy • Immunology • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

"The brief commercial run of Brii Biosciences' long-acting antibody combination of amubarvimab and romlusevimab is over. https://t.co/Beovrt8OSJ" (@FiercePharma)

BRII-196/BRII-198 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial) (clinicaltrials.gov) - P3 | N=361 | Completed | Sponsor: University of Minnesota

New P3 trial • Infectious Disease • Novel Coronavirus Disease

POST-ACUTE COVID OUTCOMES: AMUBARVIMAB/ROMLUSEVIMAB VS PLACEBO IN THE ACTIV-2 TRIAL (CROI 2023) - "While A+R was highly effective in preventing all-cause hospitalizations and deaths in high-risk outpatients with mild-to-moderate COVID-19, there was no meaningful effect of treatment on measures of Long COVID at 36 weeks. Additional interventions are needed for Long COVID prevention. Week 36 Long COVID, Hospitalizations, and Death by Amubarvimab+Romlusevimab (Active) vs Placebo Treatment"

Clinical • Novel Coronavirus Disease • Respiratory Diseases

Neutralizing monoclonal antibody in patients with coronavirus disease 2019: an observational study. (PubMed, Virol J) - "The results of this study suggest that the application of BRII-196 and BRII-198 antibody therapy improved clinical status in patients with SARS-CoV-2 delta variant infection."

Journal • Observational data • Cardiovascular • Cough • Diabetes • Fatigue • Hypertension • Infectious Disease • Metabolic Disorders • Musculoskeletal Pain • Novel Coronavirus Disease • Pain • Respiratory Diseases

Impact of combination preventative interventions on hospitalization and death under the pandemic of SARS-CoV-2 Omicron variant in China. (PubMed, J Med Virol) - "Oral antiviral medications for COVID-19 (e.g. BRII-196/BRII-198) and non-pharmaceutical interventions (NPIs) such as social distancing and antigen self-testing were considered in subsequent scenarios. Sensitivity analysis showed that interventions can be adjusted to meet certain conditions to reduce the total number of infections and deaths. In conclusion, after sufficient respiratory and ICU beds are prepared and the relaxed NPIs are in place, the SARS-CoV-2 Omicron variant would not seriously impact the health system."

Journal • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Preclinical characterization of amubarvimab and romlusevimab, a pair of non-competing neutralizing monoclonal antibody cocktail, against SARS-CoV-2. (PubMed, Front Immunol) - "In a Syrian golden hamster model of SARS-CoV-2 infection, animals receiving combination of amubarvimab and romlusevimab either pre- or post-infection demonstrated less weight loss, significantly decreased viral load in the lungs, and reduced lung pathology compared to controls. These preclinical findings support their development as an antibody cocktail therapeutic option against COVID-19 in the clinic."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Randomized, placebo-controlled, single-blind phase 1 studies of the safety, tolerability, and pharmacokinetics of BRII-196 and BRII-198, SARS-CoV-2 spike-targeting monoclonal antibodies with an extended half-life in healthy adults. (PubMed, Front Pharmacol) - P1 | " BRII-196 and BRII-198 are safe, well-tolerated, and suitable therapeutic or prophylactic options for SARS-CoV-2 infection. Clinical Trial Registration: ClinicalTrials.gov under identifiers NCT04479631, NCT04479644, and NCT04691180."

Journal • P1 data • PK/PD data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases