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Data are consistent with the results of the global Phase 3 ACTIV-2 trial, demonstrating a favorable safety and tolerability profile in people with both severe and non-severe SARS-CoV-2 infections in China
Clinical benefits were observed in efficacy indicators such as RNA conversion rate, resolution of COVID-19 symptoms, and risk of progressing to severe disease
DURHAM, N.C. and BEIJING, June 9, 2022 /PRNewswire/ -- Brii Biosciences Limited ("Brii Bio" or the "Company", stock code: 2137.HK) a multi-national company developing innovative therapies for diseases with significant unmet medical needs and large public health burdens, and TSB Therapeutics (Beijing) Co., Ltd. ("TSB Therapeutics"), a joint venture majority-owned by the Company, today announced, positive data from a randomized, single-blind clinical study (NCT04787211) of its long-acting COVID-19 neutralizing antibody therapy, the amubarvimab/romlusevimab combination, in China.
In June 2021, in parallel with the National Institutes of Health (NIH)-sponsored global ACTIV-2 Phase 3 clinical trial of the amubarvimab/romlusevimab combination, TSB Therapeutics initiated a clinical study in China to evaluate the safety, tolerability, and preliminary clinical efficacy of the combination treatment in people infected with SARS-CoV-2 (virus that causes COVID-19). Under the leadership of Prof. Nanshan Zhong, the leading principal investigator of the study, and the Guangzhou National Laboratory, the clinical centers successfully completed the enrollment of 48 subjects as planned, marking the combination therapy's first study in China.
The results of the study in China show that the amubarvimab/romlusevimab combination was generally safe and well-tolerated in both severe and non-severe SARS-CoV-2 infected subjects. No drug-related serious adverse events (SAEs), infusion reactions, dose discontinuation, or reduction due to adverse events were observed. All eight subjects with severe SARS-CoV-2 infections were enrolled and treated with the combination therapy, and their viral loads were significantly reduced from baseline levels with no subjects experiencing exacerbations that required mechanical ventilation or led to death. Among the 40 subjects with non-severe SARS-CoV-2 infections treated with the combination therapy, there were several clinical benefits observed, including RNA conversion rate (93% in treatment arm vs. 64% in placebo arm), median time to symptom resolution (8 days in treatment arm vs. 10 days in placebo arm), and proportion of progression to severe cases (0% in treatment arm vs. 5% in placebo arm). These findings are consistent with the results of the global ACTIV-2 Phase 3 trial conducted in 837 subjects.
"This is the first study of our long-acting COVID-19 neutralizing antibody therapy, the amubarvimab/romlusevimab combination, in COVID-19 patients in China. We are pleased to see that the study results further enrich the safety and efficacy of the combination therapy, providing important data for its clinical application. These data alongside the real-world data of the nearly 1,000 patients who received emergency treatment in China last year further support the currently approved indications and dosing regimen of the combination therapy in China," said Rogers Luo, President and General Manager, Greater China of Brii Bio, and Chief Executive Officer of TSB Therapeutics. "As the pandemic continues to affect the health of Chinese people, 20 Healthcare Security Administrations of provinces and cities in China have included the amubarvimab/romlusevimab combination for reimbursement under local health insurance funds. In addition, we have received purchase orders and stockpiling requests from over 20 provincial Health Commissions as well as more than 100 healthcare institutions and commercial organizations. We are rapidly advancing the preparation of our production to ensure we are in a position to provide the combination therapy to patients in need as soon as possible."
Previously, the live virus and pseudovirus testing data from multiple independent labs demonstrate that amubarvimab/romlusevimab combination retains neutralizing activity against Omicron BA.2 subvariant and all previous variants of concern. In addition, according to the preprint article posted on bioRxiv on May 26, 2022, by Prof. David Ho's team from Columbia University, in vitro pseudovirus testing data demonstrate that the IC50 of amubarvimab/romlusevimab combination against Omicron BA.4/5 subvariant is 2.445ug/ml. Based on the PK/PD model, the serum concentration of intravenous amubarvimab 1000mg and romlusevimab 1000mg on day 7 is 126-fold of the IC50 against BA.4/5 subvariant. Additional testings including live virus assays are being conducted to confirm the neutralizing activity against BA.4/5 and BA.2.12.1.
About Long-Acting COVID-19 Neutralizing Antibody Therapy, Amubarvimab/Romlusevimab Combination
Amubarvimab and Romlusevimab are non-competing SARS-CoV-2 monoclonal neutralizing antibodies derived from convalesced COVID-19 patients developed in collaboration with the 3rd People's Hospital of Shenzhen and Tsinghua University. 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.
Based on the final results from the U.S. National Institutes of Health (NIH)-sponsored ACTIV-2 Phase 3 clinical trial with 837 enrolled outpatients, the amubarvimab/romlusevimab combination demonstrates a statistically significant 80% reduction of hospitalization and death with fewer deaths through 28 days in the treatment arm (0) relative to placebo (9), and improved safety outcome over placebo in non-hospitalized COVID-19 patients at high risk of clinical progression to severe disease. 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 live virus testing data as well as pseudovirus testing data from multiple independent labs demonstrate that the amubarvimab/romlusevimab combination 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), AY.4.2 (Delta Plus), C.37 (Lambda), B.1.621 (Mu), B.1.1.529-BA.1 (Omicron), and BA.1.1 and BA.2 (Omicron subvariants).
On December 8, 2021, the National Medical Products Administration (NMPA) of China approved the amubarvimab/romlusevimab combination for the treatment of adults and pediatric patients (age 12-17 weighing at least 40 kg) with mild and normal type of COVID-19 at high risk for progression to severe disease, including hospitalization or death. The indication of pediatric patients (age 12-17 weighing at least 40 kg) is under a conditional approval. On March 15, 2022, the National Health Commission of China added the amubarvimab/romlusevimab combination to its COVID-19 Diagnosis and Treatment Guidelines (9th Pilot Edition) for the treatment of COVID-19.
In October 2021, the Company initiated and subsequently completed the rolling submission of an emergency use authorization (EUA) application with the U.S. Food and Drug Administration. In addition, the Company is pursuing additional efforts and regulatory filings for the amubarvimab/romlusevimab combination in established and emerging markets with an initial focus on securing access in countries where clinical trials were conducted and where significant gaps in access to highly effective treatments have been identified. The Company is planning further studies in China, to evaluate the use of the amubarvimab/romlusevimab combination among immunocompromised population as an additional measure of prophylaxis.
About Brii Bio
Brii Biosciences Limited ("Brii Bio", stock code: 2137.HK) is a biotechnology company based in China and the United States committed to advancing therapies for significant infectious diseases, such as hepatitis B, COVID-19, human immunodeficiency virus (HIV) infection, multi-drug resistant (MDR) or extensive drug resistant (XDR) gram-negative infections, and other illnesses, such as the central nervous system (CNS) diseases, which have significant public health burdens in China and worldwide. For more information, visit www.briibio.com.
About TSB Therapeutics
TSB Therapeutics (Beijing) Co., Ltd. ("TSB Therapeutics", or the "Company") is a holding company of Brii Bio. TSB Therapeutics was jointly established in Beijing in May 2020 by Brii Bio, the 3rd People's Hospital of Shenzhen and Tsinghua University. The Company is committed to developing the amubarvimab/romlusevimab combination. TSB Therapeutics holds exclusive rights to develop and commercialize the amubarvimab/romlusevimab combination in Greater China.
