AstraZeneca’s Evusheld Receives UK Authorization for Pre-Exposure Prophylaxis of COVID-19 in High-Risk Populations
Mar 21, 2022 01:47
CST Updated
01:47
AstraZeneca
Biopharmaceutical Manufacturer
Medicines and Healthcare products Regulatory Agency
The MHRA is an executive agency of the UK Department of Health and Social Care, responsible for ensuring that medicines and medical devices work effectively and are safe and reliable. Established in 2003 through the merger of the Medicines Control Agency and the Medical Devices Agency, the organization employs more than 1,300 staff members.
News on March 20, 2022 /BioValleyBIOON/ --AstraZeneca(AstraZeneca) recently announced that the antibody combination product Evusheld (tixagevimab and cilgavimab, research code: AZD7442) has been approved by the UK Medicines andHealth ProductsMHRA Authorization: For pre-exposure prophylaxis of COVID-19. Evidence suggests that a single dose of Evusheld provides efficacy and protection in high-risk populations (estimated to last at least 6 months).
Evusheld is indicated for adults who are currently not infected with (or exposed to) the novel coronavirus (SARS-CoV-2) and are unlikely to mount an adequate response to COVID-19 vaccination, including those for whom vaccination is not recommended. The recommended dose of Evusheld is 300mg: 150mg tixagevimab and 150mg cilgavimab, administered as two separate antibodies given sequentially via intramuscular injection. A higher dose of 600mg (300mg tixagevimab, 300mg cilgavimab) may be more suitable for certain SARS-CoV-2 variants (e.g., Omicron BA.1, Omicron BA.1.1). The use of Evusheld should be in accordance with the official guidance from the UK Department of Health and Social Care.
Evusheld is a long-acting antibody cocktail therapy composed of two monoclonal antibodies, tixagevimab (AZD8895) and cilgavimab (AZD1061), which are derived from B cells donated by convalescent patients after SARS-CoV-2 infection. These two monoclonal antibodies were discovered by Vanderbilt University Medical Center and licensed to AstraZeneca in June 2020. Tixagevimab and cilgavimab respectively target two different sites on the SARS-CoV-2 spike protein, with synergistic effects that reduce the risk of viral mutation escape.
AstraZeneca optimized these two monoclonal antibodies, extending their half-life and reducing Fc receptor and complement C1q binding. Compared with traditional antibodies, the half-life has been extended more than threefold. The purpose of reducing Fc receptor binding is to minimize the risk of antibody-dependent enhancement (ADE) of disease, a phenomenon where virus-specific antibodies enhance rather than inhibit infection and/or disease.
Tom Keith Roach, President of AstraZeneca UK, stated: "Evusheld will fill an urgent gap in the UK's fight against COVID-19 by providing protection for those who may not benefit from vaccination, often the most clinically vulnerable individuals in the community. We hope to make this critical medicine available to patients in the UK as soon as possible, as we have done in other countries."
Approximately 500,000 people in the UK are immunocompromised, and these individuals may benefit from this drug for pre-exposure prophylaxis of COVID-19. Nearly 40% of immunocompromised or immunosuppressed patients produce a lower or undetectable immune response after vaccination, and about 11% are unable to produce any antibodies. This includes patients with blood cancer,Organ TransplantationPatients taking immunosuppressive drugs later, or multiple sclerosis and similar conditionsRheumatoid ArthritisPatient.
Data from the ongoing PROVENT Phase III trial (which has met its primary endpoint) show that, compared to placebo, prophylactic treatment with AZD7442 significantly reduced the risk of developing symptomatic COVID-19 in statistical terms. The trial demonstrated that the protective effect of AZD7442 against viral infection lasted at least six months. In the trial, AZD7442 was well-tolerated, and follow-up is needed to determine the full duration of protection.
Based on the preliminary analysis of 5,172 participants (AZD7442 group N=3,441; saline placebo group, N=1,731): median follow-up of 83 days after dosing,In terms of the incidence of symptomatic COVID-19, compared with placebo, the relative risk reduction (RRR) of AZD7442 was 77% (95% CI: 46-90; p<0.001; 8/3441 [0.2%] in the AZD7442 group vs 17/1731 [1.0%] in the placebo group), and the absolute risk reduction (ARR) was 0.8%.
In subsequent analyses: With a median follow-up of 6.5 months post-administration, AZD7442 demonstrated an RRR of 83% (95% CI: 66–91; 11/3441 [0.3%] in the AZD7442 group vs 31/1731 [1.8%] in the placebo group) and an AAR of 1.5% compared to placebo.
No hospitalizations or deaths occurred in the AZD7442 treatment group. In the placebo group, there were 5 cases of severe COVID-19 and 2 COVID-19-related deaths. Adverse events were reported by 35% (1221/3461) of subjects receiving AZD7442 and 34% (593/1736) of those receiving placebo, with the vast majority being mild to moderate. The most common in the pooled analysis wereAdverse ReactionsIt is the injection site reaction.
*Existing data suggest that tixagevimab and cilgavimab may be effective for pre-exposure prophylaxis for up to six months, based on the variants prevalent during the study period. The trial is ongoing, with more data being generated to determine the exact duration of preventive protection. It remains unclear how pseudovirus or authentic SARS-CoV-2 neutralization sensitivity data correlate with clinical outcomes, but data from multiple independent studies (both pseudovirus and real "live" virus) indicate that the antibody combination retains neutralizing activity against Omicron. (Bioon.com)