- The complete dataset from this study is evolving, including important sensitivity and sub-group analysis, which will help inform whether a treatment benefit can be observed in particular subgroups of hospitalized patients.
- Additional studies of the BRII-196 and BRII-198 combination are ongoing in ambulatory COVID-19 patients through ACTIV-2 clinical trial in collaboration with NIH-NIAID.
DURHAM, N.C., United States and BEIJING, China – 3 March 2021 – Brii Biosciences (“Brii Bio”), a multi-national company , today announced that its antibodies BRII-196 and BRII-198 failed to meet pre-specified efficacy criteria permitting expansion into the Phase 3 component of ACTIV-3.
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 & Safety Monitoring Board (DSMB) 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 will work closely with the ACTIV-3 study team to further understand and to publish the data expediently.
“We anticipated that it would be very difficult to demonstrate additional benefits in the study population on top of current standard of care including VEKLURY® (remdesivir) and dexamethasone,” said Zhi Hong, Ph.D., CEO of Brii Bio. “While we are disappointed that BRII-196 and BRII-198 have not shown clear benefits during the interim analysis against COVID-19 in hospitalized patients receiving the current standard of care, we remain committed to investigating this antibody combination in ambulatory COVID-19 patients through the ongoing ACTIV-2 trial. We continue to feel confident in this therapy and its antiviral activity against the newly emerging variants. I would like to thank the ACTIV-3 study team, investigators and participants for incredible efforts, as well as NIAID for the sponsorship.”
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 (SOC) 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 BRII196 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 U.S. National Institutes of Health (NIH).
About BRII-196 and BRII-198
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 U.K. 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 U.S FDA, the Department of Health in Hong Kong, and in mainland China under an IND to the NMPA.
About Brii Biosciences
Brii Biosciences (Brii Bio) is a multi-national company committed to serving patients' needs and improving public health by accelerating the development and delivery of breakthrough medicines through partnerships, best-in-class research and development, and the disruptive application of digital and data insight. With operations in the People's Republic of China and the United States, Brii Bio is poised to serve as a bridge to carry transformative medicines to patients, help create significant growth for our partners and establish an innovation engine to help improve the public health and wellbeing of patients around the world. Brii Bio is developing treatments for illnesses with significant public health burdens, including infectious diseases, liver diseases, and CNS diseases. For more information, visit www.briibio.com.