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 (mAbs) derived from convalesced COVID-19 patients. The mAbs have been specifically engineered to reduce the risk of antibody-dependent enhancement and prolong the plasma half-lives for a 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.
This mAbs was developed in collaboration with the 3rd People's Hospital of Shenzhen and Tsinghua University. 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. In addition, in 2021, Brii Bio donated nearly 3,000 doses of the amubarvimab/romlusevimab combination for emergency use in 22 hospitals in 21 cities to ensure humanitarian access and to help curb the outbreaks of the delta variants.
The China National Medical Products Administration (NMPA) approved on December 9, 2021, 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's 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.
Based on the final results from the U.S. National Institutes of Health (NIH) - National Institute of Allery and Infectious Diseases-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 Company confirmed (Dec. 12, 2021) that an Investigational New Drug application had been submitted to the U.S. Food and Drug Administration for the combination therapy.
On March 21, 2022, the NMPA of China issued a notice to temporarily include the newly added drugs in the reimbursement guidelines by the provincial health insurance fund. Since March 22, 2022, the Healthcare Security Administrations of various provinces and cities, including Hunan, Beijing, Shanghai, Zhejiang, Jiangsu, Sichuan, Shanxi, Guizhou, Liaoning, and Anhui, have successively implemented the instructions of the notice and included amubarvimab/romlusevimab into the reimbursement of the local health insurance fund.
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 and 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 Against Omicron and BA.x Sublineages
On July 26, 2022, Brii Biosciences announced new live virus data confirming the amubarvimab/romlusevimab combination retains neutralizing activity against the Omicron BA.4/5 and BA.2.12.1 SARS-CoV-2 subvariants. Brii Bio previously 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. 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).
As of Jul. 14, 2022, the U.S. NIH OpenData Portal reported SARS-CoV-2 Variants & Therapeutics - Omicron. As does the Stanford HIVDB team website.
Amubarvimab / Romlusevimab Availability
The amubarvimab/romlusevimab combination was commercially launched in China on July 7, 2022. In the USA, the U.S. FDA is currently reviewing Brii Bio's Emergency Use Authorization application for the amubarvimab/romlusevimab combination as of July 26, 2022.
Amubarvimab / Romlusevimab 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. As of March 29, 2022, TSB Therapeutics has received purchase intention and stockpiling requests from nearly 20 provincial Health Commissions, over 100 healthcare institutions, and commercial organizations.
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 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. In addition, the Company announced on December 12, 2021, that 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 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 News
August 24, 2022 - The Company confirmed a randomized, double-blind, and placebo-controlled Phase 2 study is under planning by the First Affiliated Hospital of Guangzhou Medical University, aiming to evaluate the level of enhanced SARS-CoV-2 specific immunity after a single infusion of mAb therapy, the amubarvimab/romlusevimab combination in the immunocompromised population.
July 26, 2022 - The Company confirmed: Data from the live virus neutralization assay performed at a University of Maryland lab certified by the U.S. National Institutes of Health (NIH) and National Institute of Allergy and Infectious Diseases (NIAID) predict that total serum concentrations of the amubarvimab/romlusevimab combination will remain greater than 170 times the level required for greater than 90% neutralization (Neut99: 0.94 μg/mL) against the live virus, 14 days post-dose. As a result, adequate therapeutic exposures are expected to persist throughout the treatment period.
July 19, 2022 - Brii Biosciences Limited today announced that TSB Therapeutics Co., Ltd. is partnering with China Resources Pharmaceutical Commercial Group Co., Ltd. to advance stockpiling, channel distribution, and hospital access for the Company's amubarvimab/romlusevimab combination.
July 6, 2022 - Brii Biosciences Limited and TSB Therapeutics Co., Ltd. announced the commercial launch of the amubarvimab/romlusevimab combination, a long-acting COVID-19 neutralizing antibody therapy in China.
April 5, 2022 - A peer-reviewed study found SARS-CoV-2 BA.1 variant evades most convalescent serum and therapeutic antibodies. Other cocktail products (Amubarvimab: Romlusevimab) remained potent to varying degrees.
March 30, 2022 - Brii Biosciences Limited announced that TSB Therapeutics Co., Ltd., a joint venture majority-owned by the Company, is partnering with Sinopharm Holding Co., Ltd. to advance stockpiling, channel distribution, and regional access of the Company's long-acting neutralizing monoclonal antibody therapy, the amubarvimab/romlusevimab combination, to help contribute to COVID-19 pandemic prevention and control efforts in China.
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 China's first locally discovered and approved SARS-CoV-2 target-specific treatment.
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 treating COVID-19.
October 8, 2021 - Brii Biosciences Limited filed 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 most patients late to treatment, potentially extending its clinical benefit in a real-world setting, where rapid access to care can be challenging.
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.
