Regulatory Decision Summary for Vaxzevria

The information below summarizes the rationale for approval of the vaccine under the Food and Drug Regulations. While some of this information is already available in previous Summaries of Rationale for Approval that were published when VAXZEVRIA was authorized under the Interim Order (IO), this current summary includes updated analyses of the pooled University of Oxford studies (COV001, COV002, COV003 and COV005) and the results of a study that was not previously evaluated (D8110C00001).

COVID-19 is a serious and potentially fatal or life-threatening human infection. Vaccination is an important way to protect against the disease and help stop the pandemic.

The efficacy and safety of VAXZEVRIA is based on the pooled results of the University of Oxford studies and the data from the Phase 3 study D8110C00001.

The vaccine efficacy (VE) was demonstrated in the clinical trials. At the time of IO authorisation, interim data (data cut-off November 4, 2020) from the pooled University of Oxford studies suggested that VE against symptomatic COVID-19 fifteen (15) days post second dose was 62.1% in participants who received two standard doses of the vaccine; in the updated analysis (data cut-off December 9, 2020) which included an expanded population, the efficacy was 66.73%.

In study D8110C00001, participants received 2 doses of VAXZEVRIA or placebo given at an interval of 4 weeks, and the primary efficacy endpoint was the first case of RT-PCR confirmed symptomatic COVID-19 occurring at least 15 days post second dose. The VE was found to be 74.0%. The VE was similar in participants ≥65 years old and those with comorbidities (e.g. medically-stable chronic diseases). In terms of subjects who developed severe or critical cases of COVID-19, there were 0 cases in participants who received two doses of VAXZEVRIA (at least 15 days post second dose) as compared to 8 cases in the placebo group.

Vaccine safety was also evaluated in multiple studies.

At the time of the updated analysis from the pooled Oxford studies (data cut-off December 9, 2020), 24,244 participants ≥18 years of age had been randomised and received either one or two doses of VAXZEVRIA (n=12,282) or a control treatment (n=11,962). The safety profile observed in the pooled studies is generally consistent with that seen in study D8110C00001 (see below). Two serious adverse events (AE) were possibly related to VAXZEVRIA: one case of high fever (40.5°C) and one case of transverse myelitis.

In study D8110C00001, solicited local and systemic AEswere more common in participants who received VAXZEVRIA (n=1956) compared with placebo (n=981). The most frequently reported solicited local AEs at the site of injection after any dose of VAXZEVRIA were tenderness (68.4%) and pain (58.3%). The most frequently reported solicited systemic AEs after any dose of VAXZEVRIA were fatigue (49.7%), headache (50.2%), muscle pain (41.9%) and malaise (35.0%). Most of the solicited local and systemic AEs following VAXZEVRIA were mild to moderate in severity. In the VAXZEVRIA group, solicited local and systemic AEs reported after the second dose were generally milder and reported less frequently when compared with the first dose. The AEs were more common in younger adults (18 to < 65 years) as compared to older adults (≥ 65 years).

Unsolicited AEs, serious AEs (SAEs) and adverse events of special interest (AESI) were also reported by participants in the VAXZEVRIA group (n=21,587) and the placebo group (n=10,792). 40.6% of participants in the VAXZEVRIA group and 29.7% of participants in the placebo group reported an unsolicited AE within 28 days following any intervention. Facial paralysis occurred in 5 subjects in the VAXZEVRIA group and 0 subjects in the placebo group; these events were non-serious and a causal relationship with the vaccine could not be determined, due to the presence of underlying medical conditions which may have predisposed individuals to these events. One hundred and forty (0.6%) subjects in the VAXZEVRIA group and 78 (0.7%) subjects in the placebo group experienced a SAE. Two SAEs reported by 1 participant (hypoaesthesia and chronic inflammatory demyelinating polyradiculoneuropathy) and one SAE reported by another participant (paraesthesia) were considered related to VAXZEVRIA by the investigators. No deaths related to the vaccine were reported.

Very rare cases of anaphylactic reactions and/or hypersensitivity reactions, a combination of thrombosis and thrombocytopenia including thrombosis with thrombocytopenia syndrome, capillary leak syndrome, neurological events (including Guillain-Barré syndrome), and thrombocytopenia (including immune thrombocytopenia) following administration of the vaccine have been reported outside of clinical trials with VAXZEVRIA and are addressed through labelling and the Risk Management Plan (RMP). Important limitations of the data at this time include the lack of information on the long-term safety and efficacy of the vaccine, interactions with other vaccines, and the lack of or limited data in sub-populations (e.g. pregnant/breastfeeding women, pediatric population <18 years of age, immunocompromised patients and patients with chronic or debilitating conditions, use in subjects with severe and/or uncontrolled underlying disease). These are managed through labelling, Terms and Conditions, and the RMP.

In conclusion, based on the totality of the information, the risk-benefit profile of VAXZEVRIA is considered favourable. The efficacy of the vaccine was established and the vaccine was generally well tolerated by participants. VAXZEVRIA is therefore recommended for authorization under the Food and Drug Regulations for active immunization of individuals 18 years of age and over for the prevention of coronavirus disease 2019 (COVID-19).