- The European Union’s medicines regulator said unusual blood clotting should be listed as a “very rare” side effect of AstraZeneca’s vaccine — though it emphasized that the benefits still outweigh the risks.
- AstraZeneca released updated details of its latest clinical trial results in March. They show strong efficacy against symptomatic infection and very high efficacy against severe COVID-19.
- Results published on March 25 were based on an analysis of data from the phase 3 clinical trial, which included more than 32,000 participants in the United States, Chile, and Peru.
The European Union’s medicines regulator said April 7 that unusual blood clotting with low blood platelets should be listed as a “very rare” side effect of the COVID-19 vaccine developed by AstraZeneca.
However, the agency said the overall benefits of the vaccine still outweigh the risks.
This warning comes after a safety committee of the European Medicines Agency (EMA) reviewed 86 cases of rare blood clots — out of around 25 million people who received the vaccine in EU member countries and the United Kingdom.
The committee was unable to identify “specific risk factors” associated with clotting, but it did note that so far, most of the cases have occurred in women under 60.
Separately, the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) is recommending that people under age 30 be offered an alternative COVID-19 vaccine.
For most age groups, the benefits of the vaccine clearly outweigh the risk. But the MHRA found that this relationship was less clear for those under 30, who are much less likely to die from COVID-19.
This week, other European countries announced they were restricting use of the AstraZeneca vaccine to older adults, reports BBC News, ranging from those over 55 in France to over 60 in Germany and other countries. Denmark has suspended use of the vaccine entirely.
Scientists aren’t certain what’s specifically causing the blood clots.
One possibility is that the vaccine may cause a certain immune response in some people, similar to what’s sometimes seen in people treated with the anti-clotting medication heparin.
The EMA said people given the AstraZeneca vaccine should seek immediate medical attention if they have any of the following symptoms:
- shortness of breath
- chest pain
- swelling in the leg
- persistent pain in the abdomen
- neurological symptoms, such as persistent headaches or blurred vision
- skin bruising beyond the site of injection
AstraZeneca’s COVID-19 vaccine, which was developed with the University of Oxford, has been under scrutiny recently after several European countries temporarily halted its rollout after reports of blood clotting in some people who had received the vaccine.
Following an emergency investigation, the EMA had concluded on March 18 that the vaccine’s benefits outweigh the risks.
It said the vaccine is “not associated with an increase in the overall risk of blood clots, or thromboembolic events.”
However, additional investigation led to the agency shifting its stance this week to recommend listing clotting as a “very rare” side effect.
In response to blood clotting concerns that surfaced earlier, an independent safety board overseeing the U.S. vaccine trial and an independent neurologist carried out a more specific review of the clinical trial data.
They looked for blood clotting events including a type of brain clot called a cerebral venous sinus thrombosis.
The Data and Safety Monitoring Board (DSMB) found no increased risk of blood clotting among the more than 21,000 trial participants who had received at least one dose of the vaccine.
Certain rare events, though, may not show up during a clinical trial.
This is why the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) continue to monitor the safety of vaccines after they’re released.
The U.S. trial showed the vaccine had 76 percent efficacy against symptomatic infection, the company said March 25 in a statement.
The vaccine also showed 100 percent efficacy against severe or critical disease or hospitalization, and 85 percent overall efficacy in people 65 years or older, the company said.
The results were announced in a news release, so details are sparse. They have also not been peer-reviewed or reviewed by FDA scientists.
“The primary analysis is consistent with our previously released interim analysis, and confirms that our COVID-19 vaccine is highly effective in adults, including those aged 65 years and over,” Mene Pangalos, executive vice president of biopharmaceuticals research for AstraZeneca, said in the news release.
The company said it plans to submit an application for emergency approval to the FDA in the coming weeks.
FDA scientists will review the company’s data in depth and present its analysis to the
The company also plans to submit its full analysis to a peer-reviewed journal for publication.
The phase 3 vaccine trial included more than 32,000 adults in the United States, Chile, and Peru. Participants received either two doses of the vaccine given 4 weeks apart or an inactive placebo given at the same interval.
The most recent analysis included 190 cases of symptomatic infection, with most of the cases occurring in people who received the placebo.
“There are 14 additional possible or probable cases” that may be included in the total when the company submits its data to the FDA, the company said in its statement.
So, final efficacy results could change.
An earlier press release issued by AstraZeneca on March 22 showed 79 percent efficacy against symptomatic infection, and 100 percent efficacy against severe or critical disease and hospitalization.
However, the DSMB was concerned that the company may have included “outdated information” that could give an “incomplete view” of the vaccine’s efficacy, according to a
NIAID urged AstraZeneca to work with the DSMB to review the data, and make sure the “most accurate, up-to-date efficacy data” is shared with the public as soon as possible.
This led to the more recent results, which were not that much different from these earlier ones.
Dr. Anthony Fauci, the head of NIAID, said Tuesday on “Good Morning America” that what happened was unfortunate, calling it an “unforced error” by the company.
“The data are really quite good,” Fauci said, “but when [the company] put it into the press release, it wasn’t completely accurate.”
On Twitter, Saad B. Omer, PhD, director of the Yale Institute for Global Health, raised a common concern among clinical trial scientists about this type of public announcement by companies.
“Say it with me: data sharing through press release (without any additional material e.g. a slide set, preprint etc.) is not a good idea,” he wrote.
Fauci added that the vaccine review process includes many safeguards — including the DSMB — that ensure that vaccines approved by the Food and Drug Administration (FDA) are safe and effective.
In its press release, AstraZeneca said the vaccine was “well tolerated” by people who received it, and “no safety concerns related to the vaccine” were identified by the DSMB.
Of the participants included in the interim analysis, about 79 percent were white, 22 percent were Hispanic, 8 percent were Black, 4 percent were Native American, and 4 percent were Asian.
Around 20 percent of people in the trial were 65 years or older, and about 60 percent had health conditions linked to a higher risk of severe COVID-19, such as diabetes, severe obesity, or heart disease.
The high overall efficacy for participants 65 years or older is welcome news. Some countries that approved the AstraZeneca vaccine had initially excluded older adults from vaccination due to a lack of data on this age group in earlier trials.
Although AstraZeneca’s overall efficacy is lower than that of the Pfizer-BioNTech and Moderna vaccines, it compares favorably in terms of protecting against severe disease and hospitalization.
However, it’s difficult to directly compare the vaccines, because the clinical trials used different criteria for how to measure the outcome.
The studies were also done in different countries at different times, and with different SARS-CoV-2 variants circulating.
The results of a previous trial, published in The Lancet, suggest that waiting up to 12 weeks before giving the second dose may boost the vaccine’s efficacy.
The AstraZeneca vaccine has already been approved in more than 70 countries, the company said.
If the FDA approves the vaccine, it will bring the number of approved vaccines in the United States to four.
However, “we’re going to have millions more doses of the three licensed [vaccines] in the United States by the spring,” Dr. Sarah George, associate professor of infectious diseases at Saint Louis University School of Medicine. “So by the time [the AstraZeneca vaccine] does go through the FDA approval process, there may not be as much use for it in this country.”
The vaccine can still help other countries vaccinate their population, especially those that have been largely shut out of access to COVID-19 vaccines.
Higher-income countries such as the United States make up just a fifth of the global adult population, but they have purchased more than half of all vaccine doses, reports the Kaiser Family Foundation.
The United States has already agreed to send 4 million doses of the AstraZeneca vaccine that it’s not using to Canada and Mexico.
In March, Canada halted administration of the AstraZeneca vaccine to people under age 55 over blood clotting concerns.
The vaccine’s less rigorous storage requirements will make it easier to distribute in areas of the world without reliable access to freezer storage. It can be stored at normal refrigerator temperatures for at least 6 months.
“Cold-chain monitoring, as it is called, is a real issue with vaccines,” said George, “particularly in parts of the world where electricity supplies are minimal or not reliable.”
Both the Pfizer-BioNTech and Moderna vaccines need to be stored in a freezer until they’re thawed before use.