Monoclonal Antibodies for COVID-19: AstraZeneca and Regeneron’s Therapies Endure Contrasting Fortunes

On June 15th, AstraZeneca suffered a minor blow after its antibody cocktail for COVID-19 prevention failed to hit the primary endpoint in a Phase 3 trial. The UK drugmaker reported that its AZD7442, a long-acting antibody (LAAB) combination reduced the risk of developing symptomatic COVID-19 in patients by only a scanty 33% compared to placebo.

Although vaccinations are the most effective method to combat COVID-19, monoclonal antibody treatments could offer an alternative to those prone to severe disease or cannot get vaccinated. The FDA has previously granted emergency use authorizations to antibody cocktail therapies, namely Regeneron’s REGN-COV (casirivimab and imdevimab) and Eli Lilly’s bamlanivimab and etesevimab combo. Yet, the global demand for such COVID-19 drugs is on the high due to supply chain shortages.

AstraZeneca’s Setback

The 1,121 participant STORM CHASER trial investigated whether AZD7442 could protect individuals who have been recently exposed to symptomatic or asymptomatic COVID-19 patients in a shared household or occupational setting. Results showed that 23 out of 749 participants in the antibody cocktail group and 17 out of 372 participants in the placebo group developed symptomatic COVID-19 after coming in contact with infected patients. Overall analysis suggests that the monoclonal antibody therapy did not offer any statistically significant benefit over placebo.

However, secondary analysis offers slight promise. Post hoc subgroup analysis shows that AZD7442 reduced the risk of developing symptomatic COVID-19 by 51% versus the placebo in participants who were PCR negative at baseline and developed an infection within seven days post the injection. The number went up to 92% if infection occurred more than seven days after the injection.

“The results of STORM CHASER suggest that AZD7442 may be useful in preventing symptomatic COVID-19 in individuals not already infected. The PROVENT trial will give us more clarity in this patient population. While COVID-19 vaccination efforts have been successful, there is still a significant need for prevention and treatment options for certain populations, including those unable to be vaccinated or those who may have an inadequate response to vaccination,” said principal investigator Myron J. Levin, Professor at the University of Colorado School of Medicine.

In March, AstraZeneca modified an agreement with the US government to supply 500,000 additional doses of AZD7442 for $205 million on top of its initial deal of 100,000 doses for $486 million. However, this rests heavily on the EUA that Astra must obtain from the FDA for the therapy.

“While this trial did not meet the primary endpoint against symptomatic illness, we are encouraged by the protection seen in the PCR negative participants following treatment with AZD7442,” said Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D. “We await results from PROVENT, our pre-exposure prevention trial, and TACKLE, our treatment trial in preventing more severe disease, to understand the potential role of AZD7442 in protecting against COVID-19.”

REGN-COV Improves Survival in Hospitalized Patients

Meanwhile, earlier today, Regeneron reported that its antibody cocktail, REGEN-COV, has met the primary endpoint of the RECOVERY trial, improving survival outcomes in hospitalized COVID-19 patients who cannot elicit immune responses on their own. Trial investigators from the UK found that REGEN-COV reduced the risk of death in hospitalized patients by 20%.

“The RECOVERY trial has shown that in patients who had not made their own antibodies against SARS-CoV-2, treating them with REGEN-COV antibodies dramatically reduced their risk of dying or being on a ventilator, and also shortened how many days they remained in the hospital,” said David Weinreich, M.D., Executive VP, Global Clinical Development at Regeneron.

The 9,785 patient trial is the first large-scale study to definitively determine whether REGEN-COV reduces mortality in patients hospitalized with severe COVID-19, the company said in a statement. Results showed that REGEN-COV plus usual care reduced all-cause mortality by 20% in seronegative patients, compared to usual care alone.

“Definitive Phase 3 trials have now demonstrated that REGEN-COV can alter the course of COVID-19 infection from prevention, to very early infection, all the way through to when patients are on a ventilator in the hospital,” said George D. Yancopoulos, M.D., Ph.D., President, and Chief Scientific Officer at Regeneron.

A First in Hospitalized Patients

Previously, monoclonal antibody therapies for COVID-19 have been proven effective only in preventing hospitalizations and did not bring significant Phase 3 returns in hospitalized patients. This is the first instance where a trial has demonstrated survival benefits for antibody therapy in hospitalized patients.

“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,” said Joint Chief Investigator for the RECOVERY trial, Sir Peter Horby, Professor at the University of Oxford.

“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,” he added.

Regeneron is currently talking to the FDA to expand REGEN-COV’s EUA to treat hospitalized patients. The company is also expecting to submit a BLA for full approval later this summer.

Related Article: Novavax to Seek Regulatory Approval After COVID-19 Vaccine Displays 90% Efficacy in US Trial

Author

Rajaneesh K. Gopinath