Neutralising monoclonal antibodies (nMABs) are synthetic monoclonal antibodies that bind to the spike protein of SARS-CoV-2, preventing subsequent entry of the virus into the host cell and its replication. This effectively neutralises the virus particle. Antiviral medications inhibit viral replication and prevent progression of infection.
Recent evidence suggests that antivirals and nMABs significantly improve clinical outcomes in non-hospitalised patients with COVID-19 who are at high risk of progression to severe disease and/or death.
The interim Clinical Commissioning Policy: neutralising monoclonal antibodies or antivirals for non-hospitalised patients with COVID-19 was first published in December 2021 following recent evidence suggesting that nMABs and oral antivirals significantly improve clinical outcomes in unvaccinated non-hospitalised patients with COVID-19 who are at high risk of progression to severe disease and/or death. It was updated in January 2022.
The following products have conditional marketing authorisation for the treatment of non-hospitalised patients with COVID-19:
PF-07321332 (nirmatrelvir) plus ritonavir
Evidence: Final results from the EPIC HR trial indicate that the dual oral antiviral PF-07321332 (nirmatrelvir) plus ritonavir resulted in a relative risk reduction of hospitalisation or death by 89 percent (within three days of symptom onset) and 88 percent (within five days of symptom onset), compared to placebo in non-hospitalised, high-risk adults with COVID-19.
Marketing authorisation: PF-07321332 (nirmatrelvir) plus ritonavir administered orally has conditional marketing authorisation in Great Britain (England, Scotland and Wales) for the treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk for progression to severe COVID-19. Access to PF-07321332 (nirmatrelvir) plus ritonavir in Northern Ireland for this indication is through a Regulation 174 approval or a licensing determination by the European Medicines Agency.
Sotrovimab
Evidence: Interim analysis of the COMET-ICE trial, which studied sotrovimab administered intravenously to non-hospitalised patients with mild-to-moderate disease and at least one risk factor for disease progression, showed a relative risk reduction in hospitalisation or death at day 29 by 85 percent in patients treated with sotrovimab compared with placebo. The final analysis of this study has shown a relative risk reduction in hospitalisation or death at day 29 by 79 percent in patients treated with sotrovimab compared with placebo.
Marketing authorisation: Sotrovimab delivered intravenously has conditional marketing authorisation in Great Britain for the treatment of symptomatic adults and adolescents (aged 12 years and over and weighing at least 40kg) with acute COVID-19 infection who do not require oxygen supplementation and who are at increased risk of progressing to severe COVID-19 infection. Access to sotrovimab in Northern Ireland for the above indication is through a Regulation 174 approval or via the European Medicines Agency conditional marketing authorisation.
Remdesivir
Evidence: A three-day intravenous course of remdesivir administered within seven days of COVID-19 symptom onset to non-hospitalised patients with risk factors for disease progression, resulted in a relative risk reduction of 87 percentin hospitalisation or death at day 28.
Marketing authorisation: Remdesivir delivered intravenously has conditional marketing authorisation in the UK for the following indications:
- Treatment of COVID-19 in adults and adolescents (aged 12 years and over and weighing at least 40kg) with pneumonia requiring supplemental oxygen (low- or high-flow oxygen or other non-invasive ventilation at start of treatment), for a treatment duration of five to ten days.
- Treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk of progressing to severe COVID-19 within seven days of symptom onset, for a treatment duration of three days.
- Use of remdesivir under this policy in children aged 12-17 years would be off-label.
Molnupiravir
Evidence: Final results from the Phase 3 MOVe-OUT trial show that the oral antiviral molnupiravir administered within five days of COVID-19 symptom onset to high-risk, non-hospitalised patients resulted in a relative risk reduction of 30 percent in the composite primary outcome of hospitalisation or death at day 29.
Marketing authorisation: Molnupiravir administered orally has conditional marketing authorisation in Great Britain for use in the treatment of mild to moderate COVID-19 in adults (aged 18 years and over) with a positive SARS-CoV-2 diagnostic test and who have at least one risk factor for developing severe illness. Access to molnupiravir in Northern Ireland for this indication is through a Regulation 174 approval or a licensing determination by the European Medicines Agency.
Non-hospitalised patients are eligible for treatment with any one of the four medicines if SARS-CoV-2 infection is confirmed by either polymerase chain reaction (PCR) testing or a lateral flow test (registered via gov.uk or NHS 119) and are symptomatic with COVID-19 and showing no signs of clinical recovery and the patient is a member of a highest risk group (see definition of ‘highest’ risk groups in Appendix 1 of the Clinical Commissioning policy).
Recommendations from the Clinical Commissioning policy are:
- 1st line: PF-07321332 (may also be known as nirmatrelvir) plus ritonavir (Paxlovid®, antiviral)1 OR sotrovimab (nMAB), as clinically indicated
- 2nd line: Remdesivir IV, three days
- 3rd line: Molnupiravir PO.
Dispensing data for prescribed antivirals and nMABs for COVID-19 to 16 January 2022 reported the following:
- Ronapreve (Casirivimab/Imdevimab) (co-packaged vials) – Casirivimab 300mg plus
Imdevimab 300mg
Reporting duration: 1 Oct 2021 – 16 Jan 2022
Dispensed quantity: 20,503 - Ronapreve (Casirivimab/Imdevimab) (co-packaged vials) – Casirivimab 1332mg plus
Imdevimab 1332mg
Reporting duration: 7 Dec 2021-16 Jan 2022
Dispensed quantity: 897 - Sotrovimab (single 500mg/8ml vials)
Reporting duration: 20 Dec 2021-16 Jan 2022
Dispensed quantity: 5,609 - Molnupiravir (packs of 40x200mg capsules)
Reporting duration: 6 Dec 2021-16 Jan 2022
Dispensed quantity: 5,426
The opinions expressed in this article are those of the author. They do not purport to reflect the opinions or views of the UKCPA or its members. We encourage readers to follow links and references to primary research papers and guidance.
Competing interest statement:
The author declares: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
