The UK government announced Wednesday that it accepted a recommendation from the Medicines and Healthcare products Regulatory Agency (MHRA) to authorise emergency supply of AstraZeneca and the University of Oxford's COVID-19 vaccine AZD1222. The authorisation is for two full doses of the vaccine administered with an interval of between four and 12 weeks in individuals 18 years or older, while the regulator noted that there was not enough clear data to back a half-dose, full-dose regimen.
AstraZeneca indicated that the first doses of AZD1222 are being released on Wednesday, with Health and Social Care Secretary Matt Hancock noting that "the rollout will start on January 4 and will really accelerate into the first few weeks of next year." The drugmaker said that it aims to supply millions of doses in the first quarter of 2021 as part of an agreement with the government to provide up to 100 million doses in total. The vaccine, which uses a replication-deficient chimpanzee viral vector and contains the genetic material of the SARS-CoV-2 virus spike protein, can be stored at temperatures of 2C to 8C for up to six months.
In September, AstraZeneca and the University of Oxford began submitting data to the MHRA under a rolling review process, including results from late-stage studies that were first reported in November. The combined interim analysis from the COV002 Phase II/III trial in the UK and the COV003 Phase III study in Brazil showed that AZD1222 had an average efficacy of 70%, increasing to 90% for a regimen that included initial immunisation with a half dose followed by a full dose at least one month later. The findings indicated that the vaccine's efficacy when given as two full doses at least one month apart was 62%, with no severe cases and no hospitalisations more than 14 days after the second dose.
Munir Pirmohamed, chair of the Commission on Human medicines expert Working Group on COVID-19 vaccines, explained "we also looked at the half dose regimen, which has been publicised quite widely, but we felt that the results were not borne out by the full analysis." Meanwhile, Pirmohamed suggested that the effectiveness of AZD1222 is higher when there are three months between doses. "Effectiveness was high, up to 80%, when there was a three month interval between first and second doses, which is the reason for our recommendation," he said.
According to the MHRA, exploratory analyses suggested that increased immunogenicity was associated with a longer dose interval. Results from a further exploratory analysis that included participants who had received one dose of AZD1222 showed that vaccine efficacy was 73% from 22 days after the immunisation was given. The data indicated that there were 12 cases of COVID-19 in 7998 subjects given one dose of AstraZeneca's vaccine, compared to 44 cases in 7982 participants in the control group.
MHRA chief executive June Raine remarked "we are delighted to announce the good news that the Oxford University/AstraZeneca vaccine for COVID-19 is now approved for supply following a robust and thorough assessment of all the available data." The government formally asked the MHRA to assess the suitability of AZD1222 for temporary supply in November, shortly after the regulator initiated an accelerated rolling review of the vaccine.
The government noted that the decision to approve supply of AZD1222 was taken under Regulation 174 of the Human Medicine Regulations, which allows the temporary supply of medicines or vaccines in response to a public health need. The same process was recently used for the UK's temporary authorisation of Pfizer and BioNTech's BNT162b2, with the national rollout of the mRNA-based COVID-19 vaccine starting on December 8.
In conjunction with the latest authorisation, the UK's Joint Committee on Vaccination and Immunisation (JCVI) issued a recommendation that vaccinating more people with the first dose of AZD1222 or BNT162b2 is now a priority above offering others their second dose. The committee said that as protection is obtained around two weeks after the first dose with both vaccines, the move "will provide the greatest public health benefits in the short term and save more lives."
The MHRA clarified that the interval between doses of Pfizer and BioNTech's vaccine must be at least three weeks. The regulator added that while data demonstrate that efficacy is optimised when a second dose is administered, both vaccines offer "considerable protection" after a single dose, at least in the short term, with the second dose completing the course for longer-term protection.
AstraZeneca said that it continues to work with global regulatory authorities in support of their ongoing rolling reviews for emergency supply or conditional marketing authorisation of AZD1222. An official from the European Medicines Agency recently indicated that the company is yet to formally seek approval of the vaccine and has not provided enough information for a conditional marketing licence. Meanwhile, AstraZeneca added on Wednesday that it is seeking emergency-use listing from the World Health Organization to allow use of the vaccine in low- and middle-income countries.
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