GlaxoSmithKline and Vir Biotechnology on Monday reported final results from the Phase III COMET-ICE trial confirming that early use of sotrovimab significantly reduces hospitalisation and death in COVID-19 outpatients at high risk of worsening to severe disease. The monoclonal antibody treatment, previously known as VIR-7831, was recently given an emergency-use authorisation (EUA) by the FDA based on an interim analysis of data from about 580 patients showing it cut hospitalisation or death rates by 85% compared to placebo in this patient population.

The COMET-ICE trial randomised 1057 high-risk adults with mild or moderate COVID-19 to receive a single intravenous infusion of sotrovimab or placebo. The companies said that the primary efficacy analysis, which looked at the entire study cohort, showed that sotrovimab-treated patients were 79% less likely to be hospitalised for more than 24 hours, or die from any cause, by day 29 compared to placebo, meeting the primary endpoint.

Six patients (1%) in the sotrovimab study arm were hospitalised for >24 hours for acute management of any illness or death from any cause at day 29, versus 30 patients (6%) in the placebo group. GlaxoSmithKline and Vir said "it is possible that half of [the sotrovimab-treated] patients who were hospitalised were for reasons other than progression of COVID-19," such as small bowel obstruction, lung cancer and diabetic foot ulcer, although they noted "this was not the case for patients in the placebo arm."

NIH treatment guidelines updated

The safety analysis looked at data from 1037 participants who were followed through at least 29 days, and aside from mild-to-moderate cases of rash and diarrhoea that were more common with sotrovimab, it found no other treatment-emergent adverse events that occurred more often than placebo. The full COMET-ICE dataset will be submitted to a peer-reviewed journal.

Meanwhile, the companies said the US National Institutes of Health (NIH) has also updated its COVID-19 treatment guidelines to recommend sotrovimab for non-hospitalised patients with mild-to-moderate COVID-19 who are at high risk of clinical progression, noting that the antibody treatment "appears to retain activity against current variants of concern and interest."

Filing for full FDA approval expected in H2

GlaxoSmithKline and Vir plan to submit a marketing application to the FDA in the second half of 2021 seeking full approval of their antibody treatment. The companies also indicated that their manufacturing network is able to produce approximately 2 million doses of sotrovimab to support emergency supply in the first year following the US regulator's EUA late last month, with about 450,000 doses on hand. The antibody is also being evaluated under a rolling review by the European Medicines Agency, whose Committee for Medicinal Products for Human Use (CHMP) recently recommended that it be approved for at-risk COVID-19 patients 12 years and older.

Meanwhile, the companies are investigating intramuscular administration of sotrovimab for outpatients with mild-to-moderate COVID-19 in the COMET-PEAK study, with initial data due in the second half of 2021. Another Phase III trial, dubbed COMET-TAIL, has gotten under way as well, testing sotrovimab vis intramuscular administration for early treatment of mild-to-moderate COVID-19 in high-risk non-hospitalised adult and paediatric patients 12 years and older. Data there are anticipated in the first half of 2022.