Recently, a pharmaceutical company announced the results of a COVID-19 antibody therapy found to be effective against the whole set of mutations seen in the novel Omicron variant. Here's more on this new and promising therapy.

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COVID-19 antibody therapy

After an in-vitro experiment, the therapy, sotrovimab, was shown to be effective against 37 mutations. In vitro tests against a pseudo-virus that replicates a manufactured form of Omicron demonstrated that sotrovimab is resistant to all mutations in the Omicron variant's spike protein, and not just the crucial alterations, the pharmaceutical said on 7 December. The experiments included all 37 spike protein mutations known so far.

The pharmaceutical also announced an update to bioRxiv, a preprint server, demonstrating that sotrovimab, the investigational monoclonal antibody, retains activity against key mutations of the new Omicron SARS-CoV-2 variant (B.1.1.529), including those found in the sotrovimab binding site.

These results were acquired by doing pseudo-virus testing on certain Omicron mutations. To present, sotrovimab has proven continuous action against all World Health Organization-defined variations of concern and interest (WHO).

The businesses are now conducting in vitro pseudo-virus testing to establish sotrovimab's neutralising ability against a composite of all Omicron mutations, with the goal of providing an update by the end of 2021.

The pharmaceutical's findings come amid ongoing confusion about whether and how much Omicron weakens the defences of current medications and vaccinations. Its many mutations, notably those in the spike protein that is the focus of the majority of therapies, have prompted global worry.

The threefold reduction in sotrovimab's ability to neutralise Omicron observed in an analysis conducted by the pharmaceutical's partner should still result in a significant level of efficacy versus the variant though we have yet to see the details especially given the possibility of dosing at higher levels if necessary. The company announced last week that the medicine was effective against critical Omicron alterations, but more recent studies give more assurance that it will continue to be effective against the variation.

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Sotrovimab-related information

Sotrovimab is an experimental monoclonal antibody that neutralises SARS-CoV-2. The antibody recognises an epitope on SARS-CoV-2 that is shared with SARS-CoV-1 (the virus that causes SARS), showing that the epitope is highly conserved, making resistance development more difficult.

Updated in vitro data published in bioRxiv demonstrate that sotrovimab retains activity against all currently tested SARS-CoV-2 virus variants of concern and interest, as defined by WHO, as well as additional variants, including but not limited to Delta (B.1.617.2), Delta Plus (AY.1 or AY.2), Mu (B.1.621), and key Omicron mutations (B.1.1.529).

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The clinical development trials of sotrovimab

COMET-ICE

This was a Phase III, multicentre, double-blind, placebo-controlled study that evaluated an intravenous (IV) infusion of sotrovimab in people with mild-to-moderate COVID-19 who were not hospitalised and did not need oxygen. The final COMET-ICE study findings showed a 79 per cent decrease (adjusted relative risk reduction) (p0.001) in hospitalisation for more than 24 hours or death from any cause by day 29 when compared to placebo, satisfying the trial's main goal.

On 27 October 2021, interim data were published in The New England Journal of Medicine, and final data were pre-published on medRxiv on 8 November 2021.

COMET-TAIL

This phase III, randomised, multicentre, open-label, non-inferiority study compared intramuscular (IM) to intravenous (IV) sotrovimab for the early treatment of mild-to-moderate COVID-19 infection in high-risk, non-hospitalised adult and paediatric patients (12 years of age and older).

The main goal of the study was fulfilled, and headline findings revealed that intramuscular sotrovimab was not inferior to intravenous sotrovimab in high-risk groups. The firms intend to submit the whole COMET-TAIL data set for publication in a peer-reviewed journal in the first quarter of 2022.

COMET-PEAK

The phase II, randomised, multicentre, parallel-group study tested sotrovimab, IV and intramuscularly in outpatients with mild-to-moderate COVID-19. To date, data from open-label studies are available.

Part B of the experiment (500 mg IV vs. 500 mg IM) indicated that the IM and IV groups had comparable virological responses. The firms intend to submit the whole COMET-PEAK data set for publication to a peer-reviewed journal in due time.

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Restrictions on the approved usage

Sotrovimab is not approved for use in the following patients:

1. Those who are hospitalised as a result of COVID-19
2. Those who need oxygen treatment as a result of COVID-19
3. Those who require an increase in their baseline oxygen flow rate as a result of COVID-19 (in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity)

The benefit of sotrovimab therapy has not been shown in patients hospitalised with COVID 19. When delivered to hospitalised patients with COVID 19 who need high flow oxygen or mechanical ventilation, monoclonal antibodies against SARS-CoV-2 may be related to poor clinical outcomes.

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Adverse events

In COMET-ICE, hypersensitivity adverse events were recorded in 2% of patients treated with sotrovimab and 1% of patients treated with placebo.

The most frequently reported treatment-emergent adverse events in the sotrovimab treatment group in COMET-ICE were rash (1%) and diarrhoea (2%), both of which were classified as grade 1 (mild) or grade 2 (severe/moderate). No additional adverse events associated with therapy were observed at a greater incidence with sotrovimab than with placebo.

While the injectable antibodies are just one weapon in the COVID therapy arsenal, they may be critical for immune-compromised individuals who do not develop an appropriate response to vaccinations and may help mitigate the virus's effects in those more prone to severe illness.

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Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author is a practising super specialist from New Delhi.