Brii Bioscience (HK: 2137), a Beijing-North Carolina company, reported that its combination monoclonal antibody therapy reduced hospitalization and death in early-stage COVID-19 patients. In an interim analysis of the US Phase II/III trial that enrolled 837 non-hospitalized patients, the BRII-196/BRII-198 combination lowered hospitalization/death by 73% compared to placebo. Brii will continue analysis of subgroups to identify the clinical benefits of early (≤5 days) versus late (6-10 days) treatment, which will be useful for making clinical treatment decisions. Brii has also started a China trial of the combination therapy.  

BRII-196 and BRII-198 are non-competing SARS-CoV-2 monoclonal 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 to increase the treatment effect. Their non-overlapping epitope binding regions provide a high degree of neutralization activity against SARS-CoV-2, the company said.

Ultimately, the full analysis of the ACTIV-2 dataset will include participants enrolled in the United States, Brazil, South Africa, Mexico, Argentina and the Philippines between January and July of 2021. Brii notes that the seven-month enrollment included the rise of a number of novel SARS-CoV-2 variants. The assessment will include data on the clinical efficacy by variant type. It added that in vitro testing suggests the mAb therapy retains activity against major SARS-CoV-2 strains.

The BRII-196/BRII-198 arm of the Phase II/III ACTIV-2 trial evaluated 837 outpatients, enrolled within 10 days of symptom onset and at high risk of clinical progression (age ≥ 60 or the presence of other medical conditions at any age). Following clear trends toward statistical significance, which evaluated approximately 69% of participants through the primary endpoint in the pre-specified review, the independent data safety monitoring board allowed the early release of the results.

"We are thrilled to announce the interim Phase III results from ACTIV-2, which demonstrate a significant reduction in the endpoint of hospitalizations or death among non-hospitalized people with mild COVID-19 who were treated with BRII-196/BRII-198," said Teresa H. Evering, MD, MS, Weill Cornell Medicine, co-lead investigator of BRII-196/BRII-198 in ACTIV-2. "The devastating resurgence in COVID-19 cases over the past several months is a sobering reminder of how desperately we need treatment options."

"ACTIV-2 has shown the benefits of BRII-196/BRII-198 as a treatment for people who were at high risk for progression to severe disease and we expect that the final study results will solidify this combination monoclonal antibody treatment as a new COVID-19 therapeutic option," said Eric S. Daar, MD, Lundquist Institute at Harbor-UCLA Medical Center, co-lead investigator of BRII-196/BRII-198 in ACTIV-2.

"We are very pleased with the positive results of this important global trial," said Zhi Hong, PhD, CEO of Brii Biosciences. "As we all continue to research and evolve our understanding of this novel virus, Brii Biosciences is committed to advancing global standards of treatment for a broad range of patients at various stages of disease as well as those affected by the newly-emerging COVID-19 variants."

In early 2020, Brii Biosciences partnered with Tsinghua University and Shenzhen Third People's Hospital to establish TSB Therapeutics to develop BRII-196 and BRII-198. The Phase II China clinical trial, currently underway, is led by Dr. Nanshan Zhong, the Academician of the Chinese Academy of Engineering and Director of the National Clinical Medical Research Center for Respiratory Diseases at the First Affiliated Hospital of Guangzhou Medical University.

Brii develops therapies for infectious diseases, such as hepatitis B virus (HBV), human immunodeficiency virus (HIV), multi-drug resistant (MDR) or extensive drug resistant (XDR) gram-negative infections and other illnesses including CNS diseases. Founded three years ago, Brii was raised with $260 million in initial capital. Earlier this year, it staged a $319 million IPO on the Hong Kong Exchange.

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Disclosure: none.