EMA’s clearance of AZ vaccine in all adults leaves countries option to restrict among older adults
EMA’s conditional authorization of AstraZeneca’s COVID-19 vaccine for all adults leaves open the possibility that member states could still recommend against its use in older populations where efficacy has not been fully established.
The decision quickly followed a recommendation from EMA’s CHMP on Friday that COVID-19 Vaccine AstraZeneca (AZN1222) gain the conditional authorization in people aged 18 and older. AstraZeneca plc (LSE:AZN; NYSE:AZN) is developing the adenovirus-based vaccine in partnership with the University of Oxford.
The vaccine is the third to gain an authorization in the EU, following Comirnaty from BioNTech SE (NASDAQ:BNTX) and Pfizer Inc. (NYSE:PFE) and mRNA-1273 from Moderna Inc. (NASDAQ:MRNA).
CHMP said it based its recommendation on an overall assessment from four clinical trials in the U.K., Brazil and South Africa. Although safety was shown in all four, the committee based its determination of efficacy on two of the studies, since one U.K. study and the South African study each had fewer than six cases of COVID-19, not enough from which to draw conclusions.
Among 10,468 subjects evaluable for efficacy who received two full doses of the vaccine or placebo in the two studies, there were 64 cases of COVID-19 in the vaccine group and 154 in the placebo group, suggesting a 59.5% vaccine efficacy rate.
The update is roughly comparable to data published in The Lancet in December, showing that among 8,895 evaluable subjects, there were 27 cases in the vaccinated group vs. 71 for placebo, suggesting a 62.1% efficacy rate.
CHMP acknowledged that there were not enough data to say how well the vaccine worked in people 55 and older. In a press briefing Friday, CHMP Vice-Chair Bruno Sepodes said the committee expects it will offer some protection to older adults based on their immune responses observed in clinical studies.
At a separate press briefing, AstraZeneca’s Andrew Pollard said early studies had shown that immune responses in healthy older adults were identical to younger people, and that in larger, later-stage trials involving a broader population with a wider range of health conditions, the immune responses were only slightly reduced in older subjects, and the company expects the vaccine to be protective in that group.
At least one country would like to hear more evidence. A document posted Thursday by Germany’s health ministry said its vaccination commission recommended the use of AstraZeneca’s vaccine only in people aged 18-64, and said existing data are insufficient to make a judgment on efficacy in people 65 and older.
At AstraZeneca’s press briefing, Pollard and CEO Pascal Soriot also sought to provide assurances of efficacy in older adults in response to a reporter who said French President Emmanuel Macron called the vaccine “quasi-ineffective” in the 65-and-older group. Pollard said data thus far show “lack of evidence rather than lack of protection,” and Soriot echoed his remarks in French.
Both CHMP and AstraZeneca said upcoming results from a Phase III trial in the U.S. should add clarity. AstraZeneca’s Mene Pangalos told the briefing that the event-driven trial is fully enrolled, and the company expects data sometime in February.
In the meantime, CHMP officials said their recommendation affords countries optionality, especially with respect to the profiles of their populations.
The EMA’s authorized patient population and range of dosing intervals mirrors the U.K.’s authorization of the vaccine in late December. In both geographies, two full doses of the vaccine are given, with the second shot given 4-12 weeks after the first.
Sepodes said EMA considered data in which the intervals ranged from 3-23 weeks, but drew its conclusion from the 86% of subjects received doses within the approved range.
The Lancet publication included data from a smaller group that received a half-dose for its first shot and a full-dose subsequently. Although those data suggested a higher efficacy rate in those patients, Sepodes said EMA observed “various confounders” that made it difficult to calculate the vaccine’s efficacy in that population, and “took it out of the equation.”