The independent DSMB was concerned over the primary efficacy results shared by AstraZeneca in its interim report Monday morning.
8:30 AM Update: A few hours following a challenge over the potential of outdated information from AstraZeneca’s phase 3 US trial interim results, the company has released a statement that the efficacy rate of its COVID-19 vaccine AZD1222 reported Monday morning came from pre-specified interim analysis with a data cut-off of February 17 of this year.
"We have reviewed the preliminary assessment of the primary analysis and the results were consistent with the interim analysis," the company wrote. "We are now completing the validation of the statistical analysis."
"We will immediately engage with the independent DSMB to share our primary analysis with the most up to date efficacy data. We intend to issue results of the primary analysis within 48 hours."
In an interview on "Good Morning America" Tuesday morning, NIAID Director Anthony Fauci, MD, said the independent DSMB was concerned over the primary efficacy results shared by AstraZeneca in its interim report Monday morning.
"When they saw that press release, they got concerned, and wrote a rather harsh note to them, copied to me, saying that in fact, they felt the data that was in the press release were somewhat outdated and might in fact be misleading a bit, and wanted them to straighten it out," Fauci said.
Fauci called the incident unfortunate, and an example of an "unforced error" by AstraZeneca.
"The fact is, this is very likely a good vaccine, and this kind of thing does nothing except cast some doubt about the vaccines and maybe contribute to the hesitancy," he said. "It was not necessary. When you look at the data, they really are quite good. When they put it into the press release, it wasn't completely accurate."
7:30 AM Update: The National Institution of Allergic and Infectious Disease (NIAID) released a statement in the early hours of Tuesday morning stating the Data and Safety Monitoring Board (DSMB) had expressed concern over the newest COVID-19 vaccine data released by AstraZeneca.
Namely, the monitoring board reported to NIAID, AstraZeneca, and the US Biomedical Advanced Research and Development Authority (BARDA) that the company may have included outdated information from its 30,000-participant, phase 3 trial “which may have provided an incomplete view of the efficacy data.”
Just yesterday, AstraZeneca had reported interim data from its US-based phase 3 assessment of two-dose AZD1222, stating that the adenovirus platform prophylaxis had a 79% effectiveness in preventing symptomatic COVID-19, and 100% effectiveness in preventing severe disease, among treated adults.
Now, the NIAID is urging the company to work with the DSMB to review its efficacy data and ensure “the most accurate, up-to-date efficacy data be made public as quickly as possible.”
“Authorization and guidelines for use of the vaccine in the United States will be determined by the Food and Drug Administration and Centers for Disease Control and Prevention after thorough review of the data by independent advisory committees,” the NIAID statement concluded.
Per The New York Times, AstraZeneca had no responded to requests for comment on the NIAID statement.
This development is yet another setback in AstraZeneca’s yearlong pursuit of US regulatory consideration for AZD1222, which in May 2020 was among the very first vaccine candidates to produce promising phase 1 immunogenicity data.
Since its highly-publicized and well-resourced development with the University of Oxford, the vaccine has come across numerous obstacles.
Its US phase 3 trial was paused for 7 weeks to observe a pair of non-fatal, hospitalizing neurological adverse events in placebo participants in September 2020.
Then, South Africa health authorities announced their intention to withhold available doses of the vaccine from its frontline caregivers in February 2021 after research indicated AZD1222 was associated with approximately 20% efficacy in preventing COVID-19 in patients from the region, which was experiencing greater transmission of the B.1351 variant.
And just this month Denmark, Norway and Iceland suspended use of the product after reports of severe blood clots among vaccinated persons. Independent reviewers have since cleared the vaccine of causal association to neurological or thrombotic events.
Though the vaccine is currently authorized for use in 70-plus countries, its regulation in the US on the basis of viable phase 3 data is the difference of millions of stockpiled doses, purchased in a $1.2 billion BARDA agreement last summer, being distributed.
With rollout of the 3 previously emergency authorized COVID-19 vaccines—from Pfizer-BioNTech, Moderna, and Janssen Pharmaceuticals—the US is on track to achieve President Joseph Biden’s pledge of an available vaccine for all adults by May this year.
As of Monday morning, more than 25% of the US population had received at least 1 COVID-19 vaccine dose, and nearly 14% were fully vaccinated.