Beijing's Brii Bio (HK: 2137) reported data from a global Phase III trial that showed its combination mAb COVID-19 therapy was equally effective in patients who received the therapy in days 1-5 after onset of symptoms as those in days 6-10. The company said the data suggest the combination therapy will be effective among patients in later stages of their disease. Overall, Brii reported the candidate, which consists of two non-competing SARS-CoV-2 mAbs derived from convalesced COVID-19 patients, reduced hospitalizations and death by 78% among high-risk patients.

The Phase III trial was conducted in the US and other countries that have high levels of COVID infections. It did not include China.

Brii plans to file for US approval of the combination before the end of the year under Emergency Use rules. Last month, Brii said it had allocated $100 million for global filings and commercialization of the therapy.

Among the 837 patients in the trial, there were no deaths in the active drug cohort versus 8 deaths in the placebo group. In subjects who received treatment with BRII-196/BRII-198 within five days of symptom onset, 2% (4/196) progressed to hospitalization or death, compared with 11% (21/197) in the placebo arm.

The arm of the trial that contained subjects who were treated 6-10 days after symptom onset showed similar results:  2% (5/222) of subjects who received treatment with the combination progressed to hospitalization or death, compared with 11% (24/222) of those receiving placebo. Grade 3 or higher adverse events were less common in the BRII-196/BRII-198 arm than placebo.

BRII-196/BRII-198 exhibited neutralizing activity against pseudo-virus variants that contained spike mutations of a panel of ten commonly identified variants, including Delta. Because the pharmacokinetic (PK) profiles of BRII-196 and BRII-198 as a combination were consistent with their PK profiles as monotherapies, the data suggests there are no interactions between the two mAbs, Brii said.

"We're very encouraged by the significant reduction of hospitalizations or death among COVID-19 outpatients at high risk of clinical progression, with these interim Phase III results demonstrating that BRII-196/BRII-198 may have clinical utility in patients presenting as late as 10 days after symptom onset, providing another solution to healthcare providers and institutions that continue to deal with increasing hospital admission rates and an overburdened system," said Teresa H. Evering, MD, MS, Weill Cornell Medicine, co-lead investigator of BRII-196/BRII-198 in ACTIV-2.

"As we continue to grapple with the global effects of this pandemic, including increased incidence of disease based on current and newly-emerging variants, it is imperative that we prioritize and progress the development of safe and effective therapies for the prevention of severe disease," said Eric S. Daar, MD, Lundquist Institute at Harbor-UCLA Medical Center, co-lead investigator of ACTIV-2.

"This growing suite of positive data for combination BRII-196/BRII-198, including the consistently high risk reduction and improved safety profile across an expansive set of patients with varying disease progression, provides further validation of its potential to provide a novel therapeutic option for COVID-19 patients," said David Margolis, MD, MPH, Vice President and Head of Infectious Diseases Therapy at Brii Bio. "

Brii specializes in therapies for significant infectious diseases, such as hepatitis B, human immunodeficiency virus (HIV) infection, multi-drug resistant (MDR) or extensive drug resistant (XDR) gram-negative infections, along with other illnesses, such as the central nervous system (CNS) diseases, which have significant public health burdens in China and worldwide.

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Disclosure: none.