In a first, Regeneron's antibody cocktail reduces deaths for a subgroup of hospitalized Covid-19 patients
Scientists have come up with the first evidence that Regeneron’s antibody cocktail, which has so far only been authorized for the outpatient setting, may reduce deaths of hospitalized Covid-19 patients — albeit only a subset.
The combination of casirivimab and imdevimab is the subject of the latest data cut from RECOVERY, the large-scale UK-based trial testing a variety of potential treatments. In total, 9,785 patients hospitalized with Covid-19 were enrolled in this arm of the study and were randomly assigned to receive either usual care plus the intravenous combo or usual care alone.
Although Regeneron has burnished the profile of its drugs with new data against new variants, like Eli Lilly, its success has been limited to mild to moderate cases or as a prophylaxis. Despite an early setback among the most severe patients, the biotech is still running a trial involving patients who are hospitalized but require no or little oxygen (with initial data indicating an antiviral effect) — as the search for therapies that can help the sickest patients goes on.
The new results are thus “very exciting,” said joint chief investigator Peter Horby.
In particular, the combo appears to keep certain patients who were seronegative at baseline — meaning they had not mounted an antibody response against the virus — from dying. About one-third of the overall group were seronegative.
Focusing on this cohort for the primary analysis, investigators found that the antibody treatment reduced the 28-day mortality by 20% over usual care: 24% of the seronegative patients in the antibody group died versus 30% of the usual care arm (95% confidence interval 0·70–0·91; p=0·001). In other words, they wrote, “for every 100 such patients treated with the antibody combination, there would be six fewer deaths.”
The same effect was not seen in seropositive patients. When pooling data from this larger group as well as those with unknown status with the seronegative patients, no significant effect was reported in reducing deaths. Overall, 20% of all patients in the antibody group died compared to 21% of those who received usual care (p=0.17).
It was important to make the differentiation, said Fiona Watt — executive chair of the Medical Research Council, which funded the trial — “given the cost of drugs.”
Nonetheless, the finding that the antibody cocktail worked in any group at all was “excellent news,” according to joint chief investigator Martin Landray.
“People have been very, very skeptical, that any treatment against this particular virus would work by the time people get in hospital,” he said in a media briefing, as reported by Reuters. “If you haven’t raised antibodies of your own, you really would benefit from getting some.”
On top of a lower death rate, seronegative patients also got out of the hospital sooner, with a four-day difference in median duration of hospital stay (13 days versus 17 days for usual care group) — and 64% of them were discharged alive by day 28, compared to 58%. The numbers also suggest that if they were not on invasive mechanical ventilation at baseline, they were at lower risk of progressing to that point or dying.