Bamlanivimab continues to BLAZE through the COVID-19 gloom

Two phase III BLAZE* trials presented at CROI 2021 highlight the benefit of bamlanivimab, a potent neutralizing monoclonal antibody (nMAb), for the treatment and prevention of COVID-19.

BLAZE-2: Bamlanivimab alone

“The COVID-19 pandemic has disproportionately affected residents of skilled nursing and assisted living facilities … who are at high risk of developing severe COVID-19 … Interventions are urgently needed to protect this vulnerable population,” said the BLAZE-2 researchers.

As such, the BLAZE-2 team evaluated the efficacy and safety of bamlanivimab among residents (n=299; median age 76 years, 60 percent female) at skilled nursing and assisted living facilities. Participants were negative for SARS-CoV-2 at baseline. They were randomized to receive either IV bamlanivimab 4,200 mg or placebo. [CROI 2021, abstract 121]

By day 57, compared with the placebo arm, the bamlanivimab arm had significantly lower incidences of mild or worse COVID-19 (odds ratio [OR], 0.20) and moderate or worse COVID-19 (OR, 0.20; p<0.001 for both).

The incidence of incident SARS-CoV-2 infection by day 29 was also markedly lower among residents on bamlanivimab vs placebo (OR, 0.23; p<0.001).

Adverse event rates were balanced between the two arms. Of the 16 deaths reported, five were attributed to COVID-19, all from the placebo arm.

“[Our results suggest that] bamlanivimab was highly effective in reducing the incidence of symptomatic COVID-19 and SARS-CoV-2 infection, and was well-tolerated,” they added. “These findings demonstrate the potential beneficial impact of bamlanivimab use on COVID-19 morbidity and mortality among skilled nursing facility residents.”

BLAZE-1: Combined with etesevimab

As vaccine-derived immunity develops over time, administration of nMAbs may serve as an alternative for managing COVID-19. “[nMAbs are] immediate, passive humoural [immunotherapeutic agents] with the potential to reduce disease progression, emergency room visits, hospitalizations, and death,” said the BLAZE-1 researchers.

In the phase III part of BLAZE-1, high-risk ambulatory individuals with mild-to-moderate COVID-19 (n=1,035; mean age 53.8 years, 52 percent female) were randomized 1:1 to receive either a single IV infusion of bamlanivimab 2,800 mg combined with another nMAb – etesevimab 2,800 mg (combination arm), or placebo, within 3 days of laboratory diagnosis. [CROI 2021; abstract 122]

Day 29 saw a significantly lower incidence of COVID-19-related hospitalizations and death by any cause among those who received the combination regimen vs placebo (2.1 percent vs 6.9 percent; between-group difference, –4.8; p=0.0004).

There was also a highly significant reduction in baseline viral load among combination regimen vs placebo recipients by day 7 (between-group difference, –1.2; p<0.00000001).

AE rates were similar between the combination and the placebo arms (13 percent vs 12 percent). Of the 10 deaths reported, all were from the placebo arm, eight of which were deemed COVID-19-related.

“[These findings show that the nMAb duo] significantly reduced COVID-19-related hospitalizations and deaths among high-risk ambulatory patients and accelerated the decline in viral load and disease symptoms over time,” said the researchers.

“This study confirms that early intervention with bamlanivimab-etesevimab greatly improves clinical outcomes for high-risk ambulatory patients, and links reduction in nasopharyngeal viral load to clinically meaningful benefits,” they concluded.

The BLAZE-1 findings come on the heels of its recently reported initial results demonstrating the benefit of the bamlanivimab-etesevimab combination in the ambulatory setting. [JAMA 2021;325:632-644]