Novel mAb combo therapy cuts death risk in COVID-19 outpatients, even in late users

The monoclonal antibody (mAb) combination therapy comprising BRII-196 and BRII-198 significantly reduced the risk of hospitalization and death by more than three-quarters in non-hospitalized COVID-19 patients who were at high risk of worsening illness, according to an interim analysis of the ACTIV*-2 trial presented at IDWeek 2021.

Of note, the benefit was seen regardless of whether the treatment was initiated early (within 5 days) or late (at 6 to 10 days of symptom onset) — potentially extending its utility in the real-world setting whereby ready access to COVID-19 care can be a challenge. 

“[These] results demonstrating that BRII-196/BRII-198 may have clinical utility in patients presenting as late as 10 days after symptom onset provides another solution to healthcare providers and institutions that continue to deal with increasing hospital admission rates and an overburdened system,” said presenting author Dr Teresa Evering of Weill Cornell Medicine in New York, New York, US.

At day 28 of follow-up, BRII-196/BRII-198 led to a significant reduction by 78 percent for the combined primary outcome of hospitalization and death compared with placebo (incidence, 2.4 percent vs 11.1 percent; relative risk, 0.22; one-sided nominal p=0.00001). [IDWeek 2021, abstract LB2]

By day 28, eight patients in the placebo arm had died compared with none in the combination mAb arm. Similarly, 45 patients on placebo were hospitalized whereas only nine cases with the mAb.   

“BRII-196/BRII-198 was highly effective in reducing the risk of hospitalization or death in those with mild-to-moderate COVID-19, leading to early data release by the Data Safety Monitoring Board,” said Evering. “Efficacy [was] noted in a study conducted during a time of circulating variants of concern, including Delta.”  

The findings remained consistent even after stratifying the patients by timing of symptom onset. Clinical benefit of BRII-196/BRII-198 was seen regardless of whether the patients initiated treatment within 5 days of symptom onset (incidence of hospitalization or death, 2 percent vs 11 percent) or between 6 to 10 days of symptom onset (2 percent vs 11 percent).

“BRII-196/BRII-198 by intravenous infusion was well tolerated … [with] no serious infusion reactions or treatment-related adverse events [AEs],” reported Evering.

New grade ≥2 and grade ≥3 AEs were less frequent in the combination mAb arm than the placebo arm (14.1 percent vs 22.9 percent and 3.8 percent vs 13.4 percent, respectively).

Participants in the phase III multinational trial consisted of 837 non-hospitalized patients (median age 49 years, male 49 percent) with mild-to-moderate COVID-19 who were at high risk of progression to severe disease (age >60 years or having comorbidities such as obesity, hypertension, heart disease, diabetes, chronic kidney disease, cancer, chronic lung disease, or immunosuppressive condition). They were randomized to receive either a single dose of BRII-196/BRII-198 (given as sequential infusions) or placebo within 10 days of symptom onset.

“The devastating resurgence in COVID-19 cases over the past several months is a sobering reminder of how desperately we need treatment options,” Evering pointed out.

“We look forward to continuing to evaluate the full data set from this global trial, including the potential effects of BRII-196/BRII-198 on circulating COVID-19 variants that are driving new cases of COVID-19 around the world,” she added.

*ACTIV: Accelerating COVID-19 Therapeutic Interventions and Vaccines