01 Aug 2022
HSA GRANTS INTERIM AUTHORISATION FOR EVUSHELD FOR PRE-EXPOSURE PREVENTION OF COVID-19 IN ADULTS WHO ARE MEDICALLY UNSUITABLE FOR VACCINATION
The Health Sciences Authority (HSA), in consultation with its Medicines Advisory Committee, has, on 1 August 2022, granted an interim authorisation under the Pandemic Special Access Route (PSAR) for AstraZeneca’s antiviral monoclonal antibody, Evusheld. Evusheld comprises two monoclonal antibodies, namely tixagevimab co-packaged with cilgavimab, and is administered by intramuscular injection. It is authorised to be used for the prevention of COVID-19 in adults who have not had a known recent exposure to an individual with COVID-19 infection (pre-exposure prophylaxis) and:
- are unlikely to mount an adequate immune response to COVID‐19 vaccination due to their moderate to severe immunocompromised state from a medical condition or receipt of immunosuppressive medications or treatments; or,
- for whom COVID-19 vaccination is not recommended.
2 Pre-exposure prophylaxis with Evusheld is not a substitute for vaccination in individuals for whom COVID-19 vaccination is recommended. The treatment must be prescribed by a doctor and the suitability of use on the individual patient will require a careful clinical assessment by the prescribing doctor.
EFFICACY AND SAFETY
3 The efficacy data was based on an ongoing Phase III study in over 5,000 participants aged 18 to 99 years, who had not received COVID-19 vaccination and had risk factors for an inadequate COVID-19 vaccination response or increased risk for COVID-19 infection. The results showed that there was a relative risk reduction of symptomatic COVID-19 illness by 77% with Evusheld compared to placebo, with a duration of protection of approximately 6 months for non-Omicron SARS-CoV-2 variants. At the time the clinical study was conducted, the circulating variants of concern included Alpha, Beta, Gamma, and Delta.
4 Recent in-vitro data has shown that certain Omicron subvariants are less susceptible to Evusheld. Hence the duration of protection against the Omicron subvariants is currently unknown.
5 The safety data showed that Evusheld was well‐tolerated, and the incidence of adverse events reported in the clinical study were generally low. The common adverse events reported were mild to moderate in severity, such as headache, throat pain, runny nose, nasal congestion and muscle pain (myalgia). While the study reported a higher incidence of cardiovascular adverse events with Evusheld, the causal relationship has not been established based on current available data. HSA will continue to closely monitor for any further cardiovascular safety signal, as part of routine pharmacovigilance.
6 The available clinical evidence preliminarily demonstrated that Evusheld has a favourable benefit-risk profile for the prevention of COVID-19 in individuals who are unlikely to mount an adequate immune response to COVID-19 vaccination, or for whom COVID-19 vaccination is not recommended. Emerging data on Evusheld’s effectiveness against the currently circulating Omicron variant will be required to further determine its continued benefits. As there was no clinical data in pregnant women, breastfeeding mothers and children, no recommendation could be made in these groups.
ACTIVE MONITORING AND CONTINUOUS REVIEW OF DATA
7 As a condition for the interim authorisation under PSAR, AstraZeneca is required to collect and submit the relevant safety data from ongoing clinical studies to ensure the continued safety and efficacy of Evusheld, including its efficacy against prevailing variants. HSA will actively review the evolving effectiveness and safety data to ensure that the benefits of Evusheld continue to outweigh the known risks. PSAR interim authorisation may be terminated if new data suggests that the benefits no longer outweigh the risks. To obtain full registration for Evusheld, AstraZeneca will need to submit the complete dataset based on prevailing international standards.
HEALTH SCIENCES AUTHORITY
1 AUGUST 2022
 Medical conditions or treatments that may result in moderate to severe immune compromised state and an inadequate immune response to COVID-19 vaccination may include but are not limited to the following: immunocompromised state from solid organ transplants, blood, or bone marrow transplants, immune deficiencies, Human immunodeficiency virus (HIV) infections, use of corticosteroids, or use of other immunosuppressive medicines.
 HSA’s current requirements are based on the scientific standards set out by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH).