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Regulation

U.K. pairs green light for AZ-Oxford vaccine with aggressive distribution scheme to prioritize saving more lives

Emergency authorization prioritizes widespread vaccination via flexible dosing schedule

The U.K.’s emergency authorization of the COVID-19 vaccine from AstraZeneca and Oxford prioritizes widespread vaccination by using a flexible dosing schedule.

Dec 30, 2020 | 3:50 PM GMT

The U.K.’s emergency authorization of the COVID-19 vaccine from AstraZeneca and the University of Oxford prioritizes widespread vaccination with a flexible dosing schedule that’s supported by recent data showing up to 70% efficacy for a single dose.

The U.K.’s Medicines and Healthcare products Regulatory Agency (MHRA) announced Wednesday the emergency authorization of COVID-19 Vaccine AstraZeneca (formerly AZD1222 ). It marks the first authorization of the vaccine from AstraZeneca plc (LSE:AZN; NASDAQ:AZN) and the University of Oxford in the world.

The dosing schedule marks a departure from that of other COVID-19 vaccine authorizations. MHRA authorized a regimen of two full doses with the second dose administered 4-12 weeks after the first dose rather than the per protocol 4 weeks.

Wei Shen Lim, chairman of the U.K. Joint Committee on Vaccination and Immunisation (JCVI), said at a press briefing that the flexible dosing schedule allows the committee to recommend that the NHS prioritize getting as many at-risk individuals vaccinated with the first dose rather than offering individuals their second dose at the four-week interval.

“This will provide the greatest public health benefits in the short term and save more lives,” the committee said in a statement.

The decision effectively doubles the number of people who get dosed right away, but involves a risk that if there is a manufacturing glitch those receiving the vaccine may miss the second dose or receive it later than planned. In the U.S., Operation Warp Speed has decided to hold half of the U.S. vaccine supply in reserve to ensure the availability of the second dose of two-dose vaccine regimens. Former FDA Commissioner Scott Gottlieb has criticized this approach as being unnecessarily conservative.

JCVI said the same first-dose prioritization should be applied to Comirnaty (BNT162b2), the COVID-19 vaccine from BioNTech SE (NASDAQ:BNTX) and Pfizer Inc. (NYSE:PFE) that MHRA authorized at the start of December.

According to Lim, the latest data reviewed by MHRA showed that a single dose of AZD1222 provided up to 70% efficacy from 21 days after administration until the second dose was received. In some cases that was as long as 12 weeks in AZ’s clinical trials. Data published in The Lancet, individuals in the Phase II/III COV002 trial showed a 65.6% vaccine efficacy when the interval was greater than eight weeks between the two full doses.

Unplanned protocol shifts in the Phase III trials of the vaccine led to longer intervals between doses and have made interpretation of the pooled data difficult. For example, 85% of participants in the vaccinated group in the COV002 trial received the second dose more than eight weeks after they received the first dose.

What may have added comfort to MHRA’s recommendation for the flexible dosing interval was the observation that a longer interval between standard doses led to greater efficacy. The Lancet paper showed that for all patients who received two standard doses, vaccine efficacy was 53% when the interval between doses was less than 6 weeks, but was over 65% efficacious when the dosing interval was six weeks or more.

At the briefing, Munir Pirmohamed, chairman of the Commission on Human Medicines expert working group on COVID-19 vaccines, said MHRA had reviewed data on the dosing regimen, but found the data weren’t conclusive enough to recommend use of a regimen of a half dose followed by a full dose that had shown 90% efficacy in a subset of patients. Pirmohamed is a professor of medicine at Liverpool University.

The U.K. expects to begin vaccinations with the AZ vaccine on Jan. 4. AZ has guided to having four million doses of AZD1222 available in the U.K. by year-end, and up to 40 million doses available by March. The U.K. has ordered 100 million doses of the AZ vaccine.

AZ is in the process of submitting rolling applications in the U.S. and EU.

The U.K. has ordered 40 million doses of the Pfizer and BioNTech vaccine. A Pfizer spokesperson said the company is not disclosing its schedule for vaccine deliveries to the U.K., other than to confirm that shipments have so far been on schedule. 

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