COVID-19 immunisation set to get FDA EUA

Following the first antibody combo casirivimab+ imdevimab (REGN-COV2) from Regeneron/Roche approved in December 2020 that prevented COVID-19 in the outpatient setting (post-exposure), AstraZeneca plc, which has also conducted Phase III trials of its antibody COVID-19 combo AZD7442 within the US-funded ACTIV programm, has filed for Emergency Use Authorization (EUA) at the US Food and Drug Administration (FDA). AZD7442 is a combination of two antibodies targeting different sites in the viral spike protein and provide pre-exposure prophylaxis of symptomatic COVID-19 in non-infected individuals who do not develop sufficient antibody titers when vaccinated.

Most recently, Phase III data demonstrated a statistically significant reduction of 77% in the risk of developing symptomatic COVID-19 compared to placebo. More than 75% of participants in the PROVENT study had co-morbidities associated with an increased risk of severe disease or a reduced immune response to vaccination. The EUA request filing includes safety and efficacy data from the PROVENT and STORM CHASER Phase III trials and the Phase I trial. In the study population of the STORM CHASER trial of already infected persons, AZD7442 did not met the primary endpoint of significantly protect patients from hospitalisation.

AZD7442 combines tixagevimab (AZD8895) and cilgavimab (AZD1061), two antibodies which were derived from B-cells donated by convalescent patients after SARS-CoV-2 infection at Vanderbilt University Medical Center. Both antibodies have an extended half-life and neutralize SARS-CoV-2 viral variants such as Delta and Mu. Furthermore they showed reduced Fc receptor and complement C1q binding.

The half-life extension more than triples the durability of its action compared to conventional antibodies and could afford up to 12 months of protection from COVID-19 following a single administration. The reduced Fc receptor binding aims to minimise the risk of antibody-dependent enhancement (ADE) of disease – a phenomenon in which virus-specific antibodies promote, rather than inhibit, infection and/or disease.

Better news for patients already infected with SARS-COV-2 most recently came from Merck & Co’s (MSD)/Ridgeback Therapeutics’ antiviral molnupiravir. In infected patients with mild to moderate symptoms, the small molecule drug reduced the risk of hospitalization or death by about 50% compared to placebo in a Phase III trials. Another small molecule drug, opaganib from RedHill Pharma, prevented death in 62% of a study population of persons with with mild to moderate symptoms in a Phase II/III trial.