5 March 2021 - - China- and US-based drug developer Brii Biosciences' antibodies BRII-196 and BRII-198 failed to meet pre-specified efficacy criteria permitting expansion into the Phase 3 component of ACTIV-3, the company said.

The ACTIV-3 study evaluated the safety and efficacy of the BRII-196 and BRII-198 combination and the impact of this monoclonal antibody combination on clinical outcomes in approximately 150 hospitalized participants, relative to a standard of care comparison arm of approximately 150 participants.

As specified by protocol, data from 300 randomized patients at their day five ordinal scale were evaluated by the Data and Safety Monitoring Board for signs of clinical benefit against the current standard of care.

The DSMB determined that pre-specified efficacy criteria in this hospitalized population have not been met, and thus the study will not be expanded to enroll additional patients.

Brii Bio said it will work closely with the ACTIV-3 study team to further understand and to publish the data expediently.

The NIH's ongoing COVID-19 Therapeutic Interventions and Vaccines (ACTIV-3) master protocol is examining the clinical safety and efficacy of investigational agents, including the combination therapy of BRII-196 and BRII-198, relative to current standard of care therapy in hospitalized patients with more severe COVID-19.

An initial Phase 2 group of approximately 300 individuals, randomized 1: 1 to BRII-196 and BRII-198 or SOC, was evaluated by the DSMB for clinical improvement after 5 days, using a seven-point ordinal scale.

Following the decision not to progress into Phase 3, the evaluation of BRII-196 and BRII-198 will be unblinded, with data being submitted for publication as soon as is feasible.

This study (NCT04501978) commenced dosing with BRII-196 and BRII-198 in December 2020. The ACTIV-3 study is Sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health.

BRII-196 and BRII-198 are non-competing SARS-CoV-2 neutralizing antibodies derived from convalesced COVID-19 patients.

They have been specifically engineered to reduce the risk of antibody-dependent enhancement and prolong the plasma half-lives for potentially more durable treatment effect.

Their non-overlapping epitope binding regions provide a high degree of neutralization activity against SARS-CoV-2, with preliminary in vitro evidence suggesting continued antiviral activity against commonly circulating variants from UK and South Africa.

Phase 1 studies in healthy human volunteers in China have completed dosing and follow-up, providing safety and human PK profiles for both individual antibodies.

In addition to ACTIV-3, the BRII-196 and BRII-198 antibody cocktail is also under clinical investigation in the ongoing ACTIV-2 (NCT04518410), sponsored by the NIAID.

ACTIV-2 is a Phase 2/3 study evaluating the safety, antiviral activity and clinical efficacy investigational agents in ambulatory patients with COVID-19. The evaluation of BRII-196 and BRII-198 in ACTIV-2 will continue.

The combination of BRII-196 and BRII-198 is also being studied in Hong Kong to investigate the clinical safety and efficacy in Asian populations with COVID-19.

This study is expected to begin in 1Q 2021. BRII-196 and BRII-198 have been submitted as IND's to the US FDA, the Department of Health in Hong Kong, and in mainland China under an IND to the NMPA.

Brii Biosciences (Brii Bio) is a multi-national company with operations in the People's Republic of China and the United States. Brii Bio is developing treatments for illnesses with significant public health burdens, including infectious diseases, liver diseases, and CNS diseases.