Bamlanivimab, the monoclonal antibody authorized to treat less-severe cases of COVID-19, reduced the risk of contracting symptomatic disease among nursing home residents and staff in the placebo-controlled BLAZE-2 trial, said manufacturer Eli Lilly on Thursday.
After 8 weeks of follow-up, incidence of symptomatic COVID-19 was significantly lower among all individuals receiving the drug compared with placebo (OR 0.43).
And a pre-specified group of nursing home residents had even lower odds of symptomatic disease than those in the control group (OR 0.20), the company said.
These results of the phase III BLAZE-2 trial were announced via press release. The trial was conducted in partnership with the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, and the COVID-19 Prevention Network. Lilly promised to submit the data for peer-reviewed publication and presentation at a future medical meeting.
“The results of this innovative study further support the belief that bamlanivimab – and potentially other monoclonal antibodies – can reduce symptoms and may even prevent COVID-19,” said Myron S. Cohen, MD, CoVPN co-principal investigator and director of the Institute for Global Health and Infectious Diseases at the University of North Carolina at Chapel Hill, in a statement.
Bamlanivimab was authorized by the FDA under emergency use authorization in November to treat mild and moderate COVID-19 in patients at high risk of progressing to severe disease.
The researchers examined 965 participants (299 residents and 666 staff) who tested negative for SARS-CoV-2 at baseline. They were randomized to receive 4,200 mg of bamlanivimab or placebo. There were also 132 participants (41 residents and 91 staff) who tested positive who were included in an exploratory analysis.
There were four deaths each among both the 299 residents in the prevention arm and the 41 residents in the treatment analysis. All occurred within the placebo arm. Over the entire trial, there were 16 deaths in residents, and included those not related to COVID-19 (11 in the placebo group, five in the intervention group).
Full Results from First Part of BLAZE-1 Trial Published
While the BLAZE-2 results have yet to be published in a peer-reviewed journal, final results from the initial part of BLAZE-1 were published in JAMA on Thursday.
Compared with placebo, combination therapy with bamlanivimab and etesevimab was associated with a statistically significant reduction in SARS-CoV-2 log viral load at day 11. Yet, there was no significant difference in viral load reduction when comparing bamlanivimab monotherapy with placebo, reported Daniel Skovronsky, MD, PhD, of Eli Lilly and Company, and colleagues.
Eli Lilly previously released interim results of this study via a press release in October.
An accompanying editor’s note from JAMA associate editor Preeti Malani, MD, and JAMA deputy editor Robert Golub, MD, noted the difference between this and interim data from BLAZE-1 examining three different doses of bamlanivimab versus placebo, and found that not only were the effect sizes different, but there was also a statistically significant difference in the change in mean viral load for the 2,800 mg dose from baseline at day 11.
Malani and Golub noted that at the time of the earlier study, the placebo group was “incomplete,” which resulted in a change in primary outcome, which eliminated the statistical significance of the 2,800 mg dose of the drug.
Skovronsky and colleagues examined data from 577 non-hospitalized patients with mild or moderate COVID-19 at 49 medical centers. There were three doses of bamlanivimab included (700 mg, 2,800 mg, and 7,000 mg) and combination therapy was 2,800 mg of bamlanivimab and 2,800 mg of etesevimab.
The primary outcome was SARS-CoV-2 viral load log reduction from baseline to day 11. Secondary outcomes included proportion of patients with a COVID-19-related hospitalization, emergency department visit, or death at day 29, which was instrumental in bamlanivimab receiving an EUA, the FDA said in November.
Patients were a median age of about 45, approximately 55% were women, and 43% were Hispanic. About two-thirds had risk factors for severe COVID-19. A little under 80% had mild symptoms.
As with the interim data, the change in log viral load was not significantly different for any monotherapy group, but it was statistically significant for the combination therapy group (–0.57 [95% CI, –1.00 to –0.14], P = 0.01). Data for the proportion of patients with COVID-19-related hospitalizations or emergency department visits was 1.9% in the 2,800 mg monotherapy group, 0.9% in the combination therapy group, and 5.8% in the placebo group.
There were nine immediate hypersensitivity reactions (six bamlanivimab, two combination treatment, and one placebo). Most reactions occurred during infusion and were reported as “mild” and “not dose-related.” There were no deaths in any group.
The JAMA editors echoed criticism from experts about the unanswered questions surrounding monoclonal antibodies for COVID-19, noting that “reduction in viral load” does not “translate easily into tangible clinical outcomes.” They called for more research into the therapy, even though they acknowledged that a pandemic means making “the best decisions based on the best information available.”
“Even though monoclonal antibodies likely improve clinical outcomes in selected patients, the studies needed to answer remaining questions on the utility of treatment (which patients can benefit and in what circumstance) are unlikely to become available in a timely manner,” the editors wrote.
This study was supported by Eli Lilly and Company.
Gottlieb disclosed support from Gilead Sciences and Sentinel.
Skovronsky is an employee of Eli Lilly and Company.
Other co-authors disclosed being employees of Eli Lilly and Company, and support from Eli Lilly and Company, GlaxoSmithKline, Gilead, Viiv, Janssen, Proteus, Bristol-Myers Squibb, Theratechnologies, Amgen, Merck, Johnson & Johnson, and Pfizer.
Malani disclosed serving on the National Institute of Allergy and Infectious Diseases COVID-19 Preventive Monoclonal Antibody data and safety monitoring board.
Golub disclosed no conflicts of interest.