Antibody Combo 'Reduces Mortality in Most Vulnerable COVID Patients'

Peter Russell

June 16, 2021

An antibody combination has been found to reduce the risk of mortality by 20% when given to seronegative patients hospitalised with severe COVID-19, according to a study preprint.

The results emerged from the Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial.

The treatment uses a combination of two monoclonal antibodies, casirivimab and imdevimab (REGEN-COV, Regeneron Pharmaceuticals), that bind specifically to two different sites on the coronavirus spike protein, neutralising the ability of the virus to infect cells.

Prof Sir Martin Landray/SMC

Sir Martin Landray, professor of medicine and epidemiology at the University of Oxford, and joint chief investigator, said: "In people who are admitted to hospital with COVID, but have not managed to raise their own antibody response – their natural antibody response – giving them this combination of monoclonal antibodies in a drip, in an intravenous infusion, reduces their chances of dying, shortens their hospital stay, and reduces their chances of needing a mechanical ventilator."

Large Study

Between 18 September 2020 and May 22 this year, 9785 patients hospitalised with COVID-19 were randomly allocated to receive usual care plus the antibody combination treatment, or usual care alone.

Of these, around a third were seronegative at baseline, half were seropositive, and a sixth had unknown serostatus.

The researchers found that among seronegative patients, the antibody combination reduced the primary outcome of 28-day mortality by one-fifth compared with usual care alone.

There was "30% of mortality in the usual care group – 24% in the usual care [group] who also got the antibody combination", Prof Landray told a briefing hosted by the Science Media Centre, adding that "we can be completely convinced by that result".

Antibody combination treatment would mean that for every 100 such patients, there would be six fewer deaths, the researchers said.

Among the other main findings:

  • For the seronegative patients given the treatment, duration of hospital stay was 4 days shorter than those allocated to usual care alone

  • The proportion of patients discharged alive by day 28 was 64% in the antibody combination group compared to 58% in those who received usual care alone

  • The risk of seronegative patients needing mechanical ventilation was 30% in those who received the treatment compared to 37% in the usual care group

No benefit from the antibody treatment was seen in people who had mounted their own antibody response by the time of entry into the study, the researchers reported.

'Exciting' Results

Prof Sir Peter Horby/SMC

Sir Peter Horby, professor of emerging infectious diseases at the University of Oxford, and joint chief investigator for the RECOVERY trial, said: "These results are very exciting.

"The hope was that by giving a combination of antibodies targeting the SARS-CoV-2 virus we would be able to reduce the worst manifestations of COVID-19. There was, however, great uncertainty about the value of antiviral therapies in late-stage COVID-19 disease.

"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."

The study will be published as a pre-print on medRxiv and submitted to a journal for peer-review.

Treatment 'Could Cost Up to £2000'

Fiona Watt, executive chair of the Medical Research Council, said "This is a very important finding.

"It means that patients being hospitalised with COVID-19 can be divided into two groups based on whether or not they have made antibodies to the virus. If they do not have antibodies then treatment with antibody-based drugs to the spike protein can reduce their risk of death and also time spent in hospital.

"Patients who have made their own antibodies to the virus do not benefit from the new treatment, which is important information given the cost of drugs."

The exact cost of the treatment is not known, but likely to be in the range of £1000 to £2000, the researchers suggested.

Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine said that the benefits of an "extremely expensive drug" should not be overstated.

He added: "Reducing mortality in such people from 30% to 24% is good, but even this benefit may be less when the drug is used in practice.

"The majority of those whose condition is severe and who will die, will still die when given the drug. The benefit to those who survive is clear though and doing large well-conducted trials of this type is the way to find whether benefits are real and what their magnitude really is."

Dr George Yancopoulos, president and chief scientific officer at Regeneron, commented: "We are incredibly grateful to the RECOVERY team, participating investigators, and patients for conducting this in-depth analysis, and hope that the results mean that even more patients may soon be able to benefit from this life-saving medicine."

Prof Landray and Prof Horby were both knighted in the Queen's birthday honours list last week for their contributions to the RECOVERY trial which has previously established efficacy for dexamethasone and tocilizumab in patients hospitalised with COVID-19.

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