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Amubarvimab / Romlusevimab (BRII-196/BRII-198) Monoclonal Antibody

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January 12, 2022
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Amubarvimab / Romlusevimab (BRII-196, BRII-198) Monoclonal Antibody Description

Brii Biosciences Limited Amubarvimab / Romlusevimab (BRII-196, BRII-198) are non-competing SARS-CoV-2 monoclonal neutralizing antibodies derived from convalesced COVID-19 patients. The monoclonal antibodies (mAbs) have been specifically engineered to reduce the risk of antibody-dependent enhancement and prolong the plasma half-lives for potentially more durable treatment effect. In addition, their non-overlapping epitope binding regions provide a high degree of neutralization activity against the SARS-CoV-2 betacoronavirus.

The combination of BRII-196/BRII-198 was generally safe and well-tolerated in Phase 1 studies. In addition to the collaboration with NIAID, Brii Biosciences is conducting additional studies in China, evaluating the pharmacokinetics and safety of combination BRII-196/BRII-198 and a Phase 2 efficacy study of combination BRII-196/BRII-198 for the treatment of COVID-19.

On August 24, 2021, Brii Biosciences announced that its mAbs combination therapy, BRII-196/BRII-198, demonstrated a statistically significant reduction of 78% relative risk ([95% CI]: 0.22 [0.05, 0.86], p<0.00001 in the combined endpoint of hospitalization and death compared with placebo in 837 non-hospitalized COVID-19 patients at high risk of clinical progression, in the ongoing phase 2/3 study.

The China National Medical Products Administration (NMPA) approved on December 9, 2021, for the amubarvimab/romlusevimab combination (previously  BRII-196/BRII-198 combination), for the treatment in adults and pediatric patients (age 12-17 weighing at least 40 kg) with the mild and typical type of COVID-19, at high risk for progression to severe disease, including hospitalization or death. The NMPA approval is based on the phase 3 study final results demonstrated a statistically significant 80% (78% in interim results) reduction of hospitalization and death with fewer deaths through 28 days in the treatment arm (0) relative to placebo (9). In addition, they improved safety outcomes over placebo in non-hospitalized COVID-19 patients at high risk of clinical progression to severe disease. Furthermore, similar efficacy rates were observed in participants initiating therapy early (0-5 days) and late (6-10 days), following symptom onset, providing critically needed clinical evidence in COVID-19 patients who were late for treatment.

The Company confirmed (Dec. 12, 2021) investigational New Drug applications had been submitted for the combination therapy to the U.S. Food and Drug Administration.

Brii Bio (stock code: 2137. HK) is a multi-national company based in DURHAM, N.C., United States, and BEIJING, China, developing innovative therapies for diseases with significant unmet medical needs large public health burdens. Brii Biosciences Limited has been included as a constituent stock of the Hang Seng Composite Index. October 2021 corporate presentation. For more information, visit www.briibio.com. On Dec. 5, 2021, Brii Biosciences Limited was added to the Hong Kong Stock Connect. 

Amubarvimab / Romlusevimab Monoclonal Antibody Effectiveness Against Coronavirus Variants (Omicron)

As of January 8, 2022, the U.S. NIH OpenData Portal reported SARS-CoV-2 Variants & Therapeutics - Omicron. As does the Stanford HIVDB team website.

Brii Bio announced vitro tests against the Omicron variant in pseudovirus show that Amubarvimab/Romlusevimab Combination retains neutralizing activity against the Omicron variant and other variants of concern such as Delta and Delta Plus. The ACTIV-2 study dataset includes participants enrolled in the United States, Brazil, South Africa, Mexico, Argentina, and the Philippines between January and July of 2021 – a period of the global emergence of novel SARS-CoV-2 variants. Data on the clinical efficacy of combination BRII-196/BRII-198 by variant type will also be evaluated as part of the study. Current in vitro pseudovirus testing data suggests that combination BRII-196/BRII-198 retains activity against major SARS-CoV-2 variants of concern, including the following commonly identified variants, B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.429 (Epsilon), B.1.617.2 (Delta), and C.37 (Lambda).

Amubarvimab / Romlusevimab Monoclonal Antibody History

In early 2020, the Company partnered with Tsinghua University and Shenzhen Third People's Hospital to establish TSB Therapeutics to develop BRII-196 and BRII-198. Amubarvimab and Romlusevimab are non-competing SARS-CoV-2 monoclonal neutralizing antibodies derived from convalesced COVID-19 patients.

In less than 20 months, Brii Bio progressed the amubarvimab/romlusevimab combination from discovery to completion of Phase 3 development leading to this rapid approval by the NMPA. This approval represents the highly successful partnership with the best scientists and clinical investigators in China and around the globe on a shared mission, including the 3rd People's Hospital of Shenzhen and Tsinghua University, who discovered these neutralizing antibody leads; the U.S. National Institute of Health, the AIDS Clinical Trial Group, who sponsored and led the ACTIV-2 trial.

Amubarvimab / Romlusevimab Monoclonal Antibody Indication

BRII-196/BRII-198 Monoclonal Antibody is indicated to treat non-hospitalized COVID-19 patients at high risk of clinical progression. The indication of pediatric patients (age 12-17 weighing at least 40 kg) is under conditional approval in China. The Company announced on December 12, 2021, in vitro tests against the Omicron pseudovirus show that Amubarvimab/Romlusevimab combination retains neutralizing activity against the Omicron variant and other variants of concern such as Delta and Delta Plus.

On December 23, 2021, The Lancet published the first phase 3 clinical trial (sponsored by the University of Minnesota) to report results of anti-SARS-CoV-2 mAbs therapies with unique mechanisms (BRII-196 plus BRII-198) for the treatment of patients hospitalized with COVID-19. The results for BRII-196 plus BRII-198 suggested potential heterogeneity of treatment effect, possibly with more favorable treatment effects among patients without than with endogenous neutralizing anti-SARS-CoV-2 antibodies.

The U.S. published a Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide on December 16, 2021.

Amubarvimab / Romlusevimab Monoclonal Antibody News

December 12, 2021 - "These latest findings underscore that our combination antibody therapy holds up well against the Omicron variant that poses a significant public health threat worldwide," said Zhi Hong, Ph.D., Chairman and Chief Executive Officer of Brii Bio.

December 9, 2021 - The Company announced that China's National Medical Products Administration had approved the Company's monoclonal neutralizing antibody therapy, the amubarvimab/romlusevimab combination (previously  BRII-196/BRII-198 combination). The approval marks the first locally discovered and approved SARS-CoV-2 target-specific treatment in China.

November 25, 2021 - Local media reported: How a Chinese Covid-19 drug was created instantly – after years in the making.

November 17, 2021 - Brii Biosciences Limited announced it had received the "R&D Achievement of the Year" Award, sponsored by BayHelix, at the 2021 BioCentury China Healthcare Summit in Shanghai China. The recognition is for the R&D achievements of Brii Bio's investigational monoclonal neutralizing antibody combination therapy, BRII-196/BRII-198, for the treatment of COVID-19.

October 8, 2021 -  Brii Biosciences Limited announced the filing of an emergency use authorization application for its investigational SARS-CoV-2 combination monoclonal antibody therapy, BRII-196/BRII-198, with the U.S. FDA. 

October 3, 2021 - Brii Biosciences Limited presented interim results from Phase 3 of the ACTIV-2 trial, which showed that BRII-196/BRII-198 ("combination BRII-196/BRII-198"), the Company's neutralizing monoclonal antibody (mAb) combination therapy for the SARS-CoV-2 coronavirus, achieved a similar reduction in hospitalization or death among patients who initiated treatment early (within five days) versus late (six to 10 days) following symptom onset. These initial results suggest that combination BRII-196/BRII-198 may remain effective in a majority of patients who are late to treatment, potentially extending its clinical benefit in a real-world setting, where rapid access to care can be a challenge.

September 7, 2021 - Brii Biosciences Limited announced that the Company is committing an additional US$100 million to advance global regulatory filings and commercial efforts for its investigational SARS-CoV-2 combination therapy BRII-196/BRII-198.

August 24, 2021 - Brii Biosciences Limited announced that its SARS-CoV-2 neutralizing monoclonal antibody combination therapy, BRII-196/BRII-198, demonstrated a statistically significant reduction of 78% relative risk in the combined endpoint of hospitalization and death compared with placebo in 837 non-hospitalized COVID-19 patients at high risk of clinical progression.

July 20, 2021 - Brii Biosciences Initiates Phase 2 Clinical Trial in China for Neutralizing Antibodies, BRII-196, and BRII-198.

Amubarvimab / Romlusevimab (BRII-196/BRII-198) Monoclonal Antibody Clinical Trials

Clinical Trial NCT04787211 - The aim of this phase 2 study is to evaluate the safety and efficacy of single-dose IV infusion of BRII-196 and BRII-198 given as combination therapy in patients with severe COVID-19 and mild to moderate COVID-19 and asymptomatic carrier.