The AIDS Clinical Trials Group (ACTG), the largest global HIV research network, which has expanded its focus to include evaluating outpatient treatment for COVID-19, today announced positive data for the monoclonal antibody combination therapy BRII-196/BRII-198 from the ACTIV-2 study of Outpatient Monoclonal Antibodies and Other Therapies. In an interim analysis of the phase 3 evaluation of BRII-196/BRII-198, the combination demonstrated a 78 percent reduction in the combined endpoint of hospitalization and death compared with placebo in more than 800 non-hospitalized COVID-19 participants who were at high risk of clinical progression.

BRII-196 and BRII-198 (developed by Brii Biosciences) were derived from antibodies isolated from people who had recovered from COVID-19. Administered as two separate infusions as a one-time dose, they target two different parts of SARS-CoV-2 (the virus that causes COVID-19). In the ACTIV-2 group receiving BRII-196/BRII-198, there were 12 hospitalizations and one death, compared to 45 hospitalizations and nine deaths among the group receiving placebo. There were no safety concerns.

This interim analysis of this fully enrolled study included 837 participants who were at high risk of progressing to severe COVID-19, including being age 60 or older, being a current smoker, or having one of the following conditions: chronic lung, kidney, or liver disease; obesity; hypertension; cardiovascular disease; diabetes; or current cancer or immunosuppression. Participants were enrolled within 10 days of COVID-19 symptom onset across six countries (United States, Argentina, South Africa, Brazil, Philippines, and Mexico). Nearly two-thirds of participants had follow-up through 28 days following treatment.

The ACTG is very excited to announce such positive data from the ACTIV-2 study, particularly as we continue to see cases of COVID-19 skyrocket as a result of the Delta variant. These data offer very convincing evidence of the clinical benefit of the combination of BRII-196/BRII-198 among people at high risk of progressing to severe COVID-19."

Judith Currier, M.D., M.Sc., ACTG Chair, University of California, Los Angeles (UCLA)

Today's data were revealed by the ACTIV-2 Data Safety Monitoring Board (DSMB) based on an interim analysis of the trial. The DSMB recommended that the study continue in a blinded manner for longer term follow-up, and all participants continue to be followed.

The study will ultimately evaluate the clinical efficacy of BRII-196/BRII-198 by SARS-CoV-2 variants. Participants were enrolled during a period when a number of variants of concern were circulating, including Alpha, Beta, Gamma, and Delta. Current in vitro pseudovirus testing data suggest that BRII-196/BRII-198 is active against all major SARS-CoV-2 variants, including the Delta variant. In addition, ACTIV-2 will conduct analyses to better understand the clinical benefits of BRII-196/BRII-198 treatment among participants who received it within five days compared to within six to 10 days of symptom onset.

"The recent surge in COVID-19 hospitalizations and deaths serves as a stark reminder of the importance of early treatment for this devastating illness," said Teresa H. Evering, M.D., M.S., Weill Cornell Medicine, co-lead investigator of BRII-196/BRII-198 in ACTIV-2.

"These data suggest that BRII-196/BRII-198 will be a potent new treatment option for COVID-19," said Eric S. Daar, M.D., Lundquist Institute at Harbor-UCLA Medical Center, co-lead investigator of BRII-196/BRII-198 in ACTIV-2. "ACTIV-2 will provide us with vital insights that will help clinicians make real-world treatment decisions for the many people who continue to be affected by COVID-19."

ACTIV-2 is a randomized, blinded, controlled adaptive platform that allows promising therapies to be added and removed over the course of the study to efficiently test a variety of new agents against placebo within the same trial infrastructure. In addition to studying the safety and efficacy of investigational therapies, ACTIV-2 also aims to determine whether they can decrease viral shedding, thereby potentially preventing transmission of SARS-CoV-2.

ACTIV-2 is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), which also funds the ACTG. ACTIV-2 is part of NIH's Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), a public-private partnership program to create a coordinated research strategy that prioritizes and speeds development of the most promising treatments and vaccines. It also receives support from the Federal COVID Response – Therapeutics, the U.S. government's multi-agency effort to accelerate the development, manufacturing, and distribution of COVID-19 vaccines, therapeutics, and diagnostics. The phase 3 trial was a continuation of the phase 2 trial in which BRII-196/BRII-198 met study-defined safety and efficacy criteria.

ACTIV-2 is led by Kara W. Chew, M.D., M.S., UCLA and Davey Smith, M.D., University of California, San Diego (protocol chairs) and David Alain Wohl, M.D., University of North Carolina (UNC) and Dr. Daar (vice-chairs) and supported by Dr. Currier and Joseph J. Eron, M.D., UNC (ACTG Co-Chair).