Novel polyclonal antibody therapy meets the criteria for graduation to phase 3 in ACTIV-2 trial

The AIDS Clinical Trials Group (ACTG), the largest global HIV research network, which recently expanded its focus to include evaluating outpatient treatment for COVID-19, today announced that SAB-185, a novel polyclonal antibody therapy, has demonstrated safety and efficacy in phase 2 that meet the criteria for graduation to phase 3 in the ACTIV-2 Outpatient Monoclonal Antibodies and Other Therapies Trial (ACTG A5401).

SAB-185 is the second agent to graduate to phase 3 in ACTIV-2, which is evaluating multiple investigational agents to treat early, symptomatic COVID-19 in non-hospitalized individuals. The combination monoclonal antibody treatment BRII-196/BRII-198 graduated to phase 3 in May 2021 and recently reported positive data.

SAB-185 (developed by SAB Biotherapeutics), is the first polyclonal antibody (a treatment containing a variety of targeted, highly potent antibodies) to be evaluated in ACTIV-2. SAB-185 is made by Tc Bovines™ that have been genetically engineered to make fully human antibodies. Once the bovines develop an immune response and generate antibodies against the spike protein on the surface of SARS-CoV-2 (the virus that causes COVID-19), their plasma is collected, and the antibodies are separated out and purified.

The graduation of SAB-185 from phase 2 to phase 3 in ACTIV-2 is an important milestone as we evaluate a variety of potential treatments for people who have COVID-19 but aren't sick enough to be hospitalized. We are thrilled that, per the study protocol, the interim analysis of phase 2 data from participants receiving SAB-185 demonstrated sufficient safety and efficacy to justify advancement to phase 3."

Judith Currier, M.D., M.Sc., University of California, Los Angeles

The phase 2 study of SAB-185 evaluated two doses, both of which met pre-defined criteria for graduation to phase 3. Evaluations are ongoing to determine which of these doses will advance to phase 3. The planned phase 3 study will evaluate the safety and efficacy of SAB-185 to prevent hospitalization and death in non-hospitalized adults with COVID-19. The study will enroll 1,200 participants at high risk of progressing to severe COVID-19. Half of the participants will receive SAB-185 and half will receive casirivimab and imdevimab, Regeneron's combination monoclonal antibody treatment. Both will be administered as an intravenous infusion.

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 within the same trial infrastructure.

"We are pleased to advance a second agent to phase 3 in the ACTIV-2 study," said Babafemi Taiwo, M.B.B.S., Professor of Medicine and Chief of Infectious Diseases at Northwestern University and lead investigator of SAB-185 in ACTIV-2. "We are especially enthusiastic about the first polyclonal antibody therapy being evaluated in ACTIV-2. Because it contains a diverse mix of antibodies, SAB-185 can simultaneously attack SARS-CoV-2 at different points, rendering it a very promising treatment option."

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 Eric S. Daar, M.D., Lundquist Institute at Harbor-UCLA Medical Center (vice-chairs) and supported by Dr. Currier and ACTG Co-Chair Joseph J. Eron, M.D., UNC.

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 the 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.