In the Oxford University-based RECOVERY trial, the combination of casirivimab and imdevimab reduced the risk of death by a fifth in patients hospitalised with severe COVID-19 who had not developed antibodies of their own.
Further informationPre-print study results
It also significantly reduced the length of hospital stay in these patients and their likelihood of needing a ventilator to breathe.
Casirivimab and imdevimab, being developed by Regeneron, bind to two different sites on the coronavirus spike protein, neutralising the ability of the virus to infect cells.
Sir Martin Landray, professor of medicine and epidemiology at the University of Oxford, and joint chief investigator for the RECOVERY trial, said: ‘We now know that this antibody combination is not only bad for the virus but it is also good for the sickest patients who have failed to mount a natural immune response of their own. That is excellent news – it is the first time that any antiviral treatment has been shown to save lives in hospitalised COVID-19 patients.'
Between 18 September 2020 and 22 May 2021, 9785 patients hospitalised with COVID-19 were randomised to receive usual care plus the antibody combination (casirivimab 4g with imdevimab 4g by intravenous infusion) or usual care alone.
Around one third of participants were seronegative at baseline, half were seropositive, and one sixth had unknown serostatus. Among patients who received usual care alone, 28-day mortality was twice as high in those who were seronegative (30%) as those who were seropositive (15%) at study entry.
Among patients who were seronegative at baseline, preliminary results showed the antibody combination significantly reduced the primary outcome of 28-day mortality compared with usual care alone (24% of patients in the antibody combination group died vs 30% of patients in the usual care group). For every 100 such patients treated with the antibody combination, the researchers calculate there would be six fewer deaths.
Results showed the antibody combination was only beneficial in seronegative patients. When combining the larger seropositive group (as well as those with unknown status) with the seronegative patients, there was no significant effect on 28-day mortality (overall 20% of patients in the antibody combination group died vs 21% of patients in the usual care group).
For the seronegative patients, the duration of hospital stay was four days shorter (median 13 days vs 17 days) among those allocated to the antibody combination than those allocated to usual care, and the proportion of patients discharged alive by day 28 was greater (64% vs 58%). Among the seronegative patients not receiving invasive mechanical ventilation at baseline, the risk of progressing to invasive mechanical ventilation or death was lower among those allocated to the antibody combination than the usual care group (30% vs 37%).
Sir Peter Horby, professor of emerging infectious diseases at the University of Oxford, and joint chief investigator, called the results 'very exciting,' adding: 'It is wonderful to learn that even in advanced COVID-19 disease, targeting the virus can reduce mortality in patients who have failed to mount an antibody response of their own.’
Professor Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, said: 'It is very good to know that drugs, targeted at the virus itself, can affect the outcome in patients in hospital.'
However, he cautioned: 'The absolute magnitude of benefit in mortality is not large, and it means that a large (possibly 20) number of people have to be treated with the extremely expensive drug for a single death to be prevented.
'The costs of these drugs tends to be very high, and the calls for cheaper vaccines might be repeated for these drugs, which are essentially only available in very rich countries.'