AstraZeneca on Monday announced that its vaccine AZD1222 demonstrated efficacy of 79% at preventing symptomatic COVID-19 in a late-stage study conducted in the US. Results also showed that the vaccine had 100% efficacy at preventing severe disease and hospitalization, with comparable effectiveness across ethnicity and age, with 80% efficacy in those aged 65 years and over.
“We are thrilled by the results,” remarked Ruud Dobber, executive vice president of AstraZeneca’s biopharmaceuticals business unit, noting that “the plan is to file in the first half of April for the emergency-use authorization.” Dobber added “assuming that the approval will take place in a fast way, we hope to deliver 30 million doses instantly after the EUA for Americans to get vaccinated.”
The phase 3 trial, dubbed D8110C00001, began in September last year and is being funded by the US Biomedical Advanced Development Authority (BARDA) as part of Operation Warp Speed. However, the study has faced delays, with a pause in the US lasting around 6 weeks whilst the FDA probed possible neurological side effects that emerged in two participants who received AZD1222 in other trials.
Results “offer confidence”
In the D8110C00001 study, 32,449 participants in the US, Peru and Chile were randomized to receive two doses of AZD1222 or saline placebo administered at a 4-week interval. According to AstraZeneca, the interim analysis is based on 141 symptomatic cases of COVID-19, defined as SARS-CoV-2 RT-PCR-positive symptomatic illness ≥15 days after the second dose. Mene Pangalos, executive vice president of biopharmaceuticals R&D, noted on a media briefing that at the interim analysis, there were five cases of severe disease and hospitalization in the placebo group, versus none in those given AZD1222.
Ann Falsey, co-lead principal investigator for the trial, said the results “offer confidence that adults of all ages can benefit from protection against the virus.” The drugmaker noted that approximately 20% of study subjects were 65 years and over, and approximately 60% had co-morbidities associated with an increased risk for progression of severe COVID-19, such as diabetes, severe obesity or cardiac disease.
No increased risk of thrombotic events
Meanwhile, AstraZeneca said that the vaccine was well tolerated, adding that the study’s independent data safety monitoring board (DSMB) did not identify any safety concerns. The company indicated that the DSMB conducted a specific review of thrombotic events, as well as cerebral venous sinus thrombosis (CVST), finding no increased risk of thrombosis or events characterised by thrombosis among the 21,583 participants receiving at least one dose of the vaccine.
The safety findings come shortly after some countries in Europe suspended use of AZD1222 after a number of reports of serious side effects, including seven cases of disseminated intravascular coagulation and 18 cases of cerebral vein thrombosis. However, a subsequent review by the European Medicines Agency determined that the vaccine is safe and effective, whilst it is not associated with an overall higher risk of thromboembolic events.
Efficacy better than expected
Commenting on the latest results, Jefferies analyst Peter Welford said “efficacy is better than we had expected,” adding “importantly, after recent largely unfounded safety concerns in Europe, the study confirms the safety profile.” AstraZeneca released late-stage results last year from studies conducted in the UK and Brazil, with pooled interim data suggesting that AZD1222 had an average efficacy of 70%, increasing to 90% for a regimen that included initial immunisation with a half dose.
AZD1222, which was co-invented by the University of Oxford and its spin-out company Vaccitech, uses a replication-deficient chimpanzee viral vector that contains the genetic material of the SARS-CoV-2 virus spike protein. The vaccine has been granted a conditional marketing authorisation or emergency use in more than 70 countries.