AstraZeneca Eyes EUA for COVID-19 vaccine after Positive Results

AstraZeneca has released positive safety and efficacy results from a large Phase III study in the United States, Chile, and Peru for the COVID-19 vaccine – and in particular, there is no increased risk for blood clots according to the 30 reported in Europe earlier. month.

The pharma giant released results from a Phase III test D8110C00001 (NCT04516746), showing that the vaccine was 79% effective in preventing symbolic COVID-19 and 100% effective in preventing severe infection. or hospital in the whole group. It was also 80% effective in preventing symptomatic disease in people over 65 that made up 20% of participants, the company said.

The non-replicated adenoviral vector vaccine targeting SARS-CoV-2 is known as AZD1222 in the United States, where it has not been approved or authorized for emergency use. The positive results should drive the vaccine toward final FDA approval, one analyst said yesterday.

“With this favorable reading, discouraging manufacturing or other issues identified during the review process, we believe the FDA is likely to grant access to the drug,” said Andrew Berens, MD , director of management, focused oncology, and senior research analyst at SVB Leerink, wrote with a colleague in a research note.

However, the NIH National Institute for Allergies and Infectious Diseases (NIAID), issued a statement early Tuesday morning citing concerns raised by the Data and Safety Review Board (DSMB) of the study, which contacted NIAID; The U.S. Biomedical Advocacy and Development Authority (BARDA), which funded the lawsuit; and AstraZeneca that the company could “extract old-fashioned information from that test, which may have provided an incomplete view of the efficiency data.”

“We urge the company to work with the DSMB to review the efficiency data and ensure that the most up-to-date efficiency data is made public as soon as possible,” said NIAID.

AstraZeneca responded Tuesday with a statement saying its data was based on a pre-determined interim analysis with a data cut on February 17, and that its initial evaluation of its main study showed consistent results. the interim analysis: “We are now finalizing the validation of the statistical analysis.”

Peter Welford, an equality analyst at Jefferies, described the results as “surprisingly optimistic” in a research note. It also offered two possible explanations for why the effectiveness rate of AstraZeneca lagged behind the 95% final efficacy reported by Pfizer and BioNTech for their BNT162b2 vaccine, and the reported 94.1% ultimate efficacy. by Moderna for the mRNA-based COVID-19 vaccine (mRNA-1273). Both have been approved for U.S. emergency use by the FDA.

“(1) Weekly swabs were performed to detect COVID-19 and not just confirmation of suspected cases with symptoms as in US trials; and (2) MenACWY meningococcal vaccine used as a comparator and not it’s a placebo, ”Welford wrote.

Welford, however, said the AstraZeneca vaccine offered a significant advantage over the other two COVID-19 vaccines when it came to easy storage:

“Importantly, AZD1222 offers a simple supply chain facility, with the vaccine capable of being stored and transported at normal cooling conditions (2–8ºC) for at least six months, without the need for special administration conditions. This compares favorably with supply chain supply for mRNA vaccines from Pfizer / BioNTech and Moderna, which can only be stored at cooling temps for 5 and 30 days, respectively, and require transport at -70ºC and -20ºC, separately. “

Controversy about clots

The AstraZeneca vaccine has been renamed the AstraZeneca COVID-19 vaccine in Europe and the UK, where it was first developed through a collaboration between Oxford University and its other company, Vaccitech, before AstraZeneca joined the company. -operation.

The AstraZeneca / Oxford vaccine has caused a great deal of controversy in Europe in recent months, initially due to its lack of data in people over 65, and recently about potential concerns increase the risk of blood clots, based on what the World Health Organization said earlier this month as reports of 30 patients who developed thrombotic events after receiving the vaccine.

The reports prompted more than a dozen European countries to suspend their vaccination of patients using the AstraZeneca two-dose vaccine. But on Thursday, both the European Medicines Agency and the UK Medicines and Healthcare products Regulatory Agency (MHRA) acknowledged that the benefits of the vaccine outweighed its risks.

The AstraZeneca COVID-19 vaccine has been granted conditional marketing license or emergency use in more than 70 countries across six continents. In addition, the World Health Organization has provided the vaccine with an Emergency Use List, accelerating access in up to 142 countries through the COVAX Facility.

32,449 participants

D8110C00001 was a large trial, with 32,449 participants randomly assigned to the vaccine – two doses with a four-week interval – or placebo in a 2: 1 ratio, with approximately 21,583 partner receives the vaccine. In total, 141 simulated cases of COVID-19 occurred during the trial.

The vaccine was well received and no significant safety concerns were raised by the trial. The independent data safety review board of the trial reviewed thrombotic events in addition to cerebral venous sinus thrombosis (CVST) with the assistance of an independent neurologist, simply so that there was no increased risk of such events or CVST in the 21,583 participants received at least one dose of the vaccine.

Participants in the interim analysis of the US-Chile-Peru test included approximately 79% white / Caucasian, 8% black / African American, 4% Native American, 4% Asian, and 22% Hispanic.

In addition, AstraZeneca reported, approximately 20% of participants were 65 years or older, and approximately 60% had comorbidities associated with an increased risk for progression of COVID-19 malignancy, such as diabetes, obesity, or heart disease.

“These findings confirm results seen previously in AZD1222 tests across all adult populations but it is encouraging to see similar efficacy results in people over 65 for the first time,” said Ann Falsey, MD, professor at the University of Rochester School of Medicine, and co-principal investigator for the case.

Added Mene Pangalos, executive vice president, R&D biopharmaceuticals, AstraZeneca: “These findings add to the growing body of evidence showing that this vaccine is well tolerated. and highly effective against all species of COVID-19 and across all age groups. We are confident that this vaccine can play an important role in protecting millions of people around the world against this deadly virus. “

To that end, AstraZeneca said, they are preparing to submit their data to the FDA “in the coming weeks” as they seek emergency use approval (EUA) for its vaccine. A major study of the U.S. Phase III test will be submitted for publication in a peer-reviewed journal, the company said.

The positive results achieved in D8110C00001 were higher than those in the initial tests of the vaccine.

“This analysis confirms the AstraZeneca COVID-19 vaccine as a much-needed additional vaccine option, offering confidence that adults of all ages will benefit from protection against the virus,” Falsey said.