Virus World

The United States can immediately resume use of Johnson & Johnson's (JNJ.N) COVID-19 vaccine, top health regulators said on Friday, ending a 10-day pause to investigate its link to extremely rare but potentially deadly blood clots. The Centers for Disease Control and Prevention (CDC) and Food and Drug Administration said the risks of experiencing the syndrome involving severe blood clots and low platelets as a result of the vaccine was very low. They found 15 cases in the 8 million shots given. "We are no longer recommending a pause in the use of this vaccine," CDC Director Rochelle Walensky told a news briefing. "Based on the in-depth analysis, there is likely an association but the risk is very low."  Top U.S. FDA officials said the decision was effective immediately, clearing the way for shots in arms as early as Saturday. The agency said it would warn of the risk in an updated fact sheet given to vaccine recipients and providers. The agencies made the decision following a meeting of outside advisers to the CDC who recommended that the vaccine pause be ended. In an analysis presented at the meeting, CDC staff said that the cases of the syndrome that they had found occurred at a rate of seven per one million doses in women under age 50, with the highest risk occurring among women ages 30 to 39. For women over age 50 and for all men, the clots appeared at a rate of one per one million doses, the analysis showed. In all, there were three deaths, officials said.

After a day-long meeting, the CDC panel voted 10-4 that the J&J vaccine be used as recommended in people 18 years of age and older, the parameters of its current FDA authorization. Dr. Jesse Goodman, an infectious disease expert at Georgetown University in Washington and a former chief scientist at the FDA, said the risk was not trivial, but still small. "But we should keep it in perspective. I mean the risk of dying from a car accident in your life is something like one in 100, the risk of being struck by lightning is something like one in 15,000," Goodman said. Unlike the highly effective vaccines by Pfizer Inc (PFE.N) and Moderna Inc (MRNA.O), which require two doses and must be kept frozen at ultra-cold temperatures, J&J's vaccine can be given in a single dose and stored at regular refrigeration temperatures, making it a better option for hard-to-reach areas. Johnson & Johnson shares closed up 0.2% at $165.52.  "We will collaborate with health authorities around the world to educate healthcare professionals and the public to ensure this very rare event can be identified early and treated effectively," J&J's Chief Scientific Officer Paul Stoffels said in a statement after the agencies made their announcement. When the agencies first announced the pause, they urged doctors to avoid using the blood thinner heparin, commonly given to patients to break up blood clots, in people who had received the J&J vaccine and were experiencing blood clots and low blood platelets.  In the cases of the vaccine-induced blood clots, however, heparin appears to make the condition worse. Walensky said doctors heeded that warning, noting that the drug had not been used in any of the cases identified after the pause began.

The U.S. decision follows a similar one by the European Medicines Agency, which on Tuesday said the benefits of the J&J shot outweighed its risks and recommended adding a warning about unusual blood clots with low blood platelet counts to the vaccine’s product label. J&J resumed its rollout there.  The J&J probe followed an investigation in Europe of the AstraZeneca PLC(AZN.L) vaccine, with which similar cases of blood clots were first identified. Dr. Peter Marks of the FDA said the cases appear so similar that a doctor would not be able to tell which vaccine caused them.  Both the J&J and AstraZeneca vaccine use different versions of a cold virus to deliver instructions for making coronavirus proteins into cells to produce an immune response. Marks said studies are underway to determine whether the adenovirus or something else is behind the rare blood clots. Dr. William Moss, executive director of the International Vaccine Access Center at the Johns Hopkins Bloomberg School of Public Health, said the J&J vaccine will help advance the vaccination effort. "Giving people the choice to receive a single-dose vaccine will help get more people vaccinated faster and will better protect some populations, such as those who are homeless or incarcerated," Moss said by email. J&J has faced several setbacks since its vaccine gained U.S. emergency authorization in February, including drawing scrutiny over production shortfalls. In the United States, 35% of adults are fully vaccinated and 53% have received at least one shot, according to CDC data. The United States leads the world with roughly 570,000 COVID-19 deaths.

AstraZeneca Plc's COVID-19 vaccine trial in the United States is expected to resume as early as this week after the U.S. Food and Drug Administration completed its review of a serious illness in a study participant, four sources told Reuters. AstraZeneca’s large, late-stage U.S. trial has been on hold since Sept. 6, after a participant in the company’s UK trial fell ill with what was suspected to be a rare spinal inflammatory disorder called transverse myelitis. The sources, who were briefed on the matter but asked to remain anonymous, said they have been told the trial could resume later this week. It was unclear how the FDA would characterize the illness, they said. An FDA spokeswoman declined to comment.

The agency is requiring researchers conducting the trial to add information about the incident to consent forms signed by study participants, according to one of the sources.  The agency is requiring researchers conducting the trial to add information about the incident to consent forms signed by study participants, according to one of the sources. “In this case, after considering the information, the independent reviewers and MHRA (Medicines and Healthcare products Regulatory Agency) recommended that vaccinations should continue,” the draft consent form stated. “Close monitoring of the affected individual and other participants will be continued.” Regulators in Brazil, India and South Africa also previously allowed AstraZeneca to resume its vaccine trials there.

AstraZeneca, which is developing the vaccine with Oxford University researchers, had been seen as a frontrunner in the race to produce a vaccine for COVID-19 until its trials were put on hold to investigate the illness. Early data from large-scale trials in the United States of vaccines from Pfizer Inc PFE.N and Moderna Inc MRNA.O are expected some time next month. Johnson & Johnson JNJ.N last week paused its Phase III COVID-19 vaccine trial to investigate an unexplained illness in a study participant. At the time of the announcement, the company did not know whether the volunteer had been given its vaccine or a placebo. A J&J spokesman on Tuesday said the study remains on pause as the company continues its review of medical information before deciding to restart the trial. J&J noted last week that its “study pause” was voluntary. By contrast, AstraZeneca’s trial is on “regulatory hold,” which is imposed by health authorities...

“We should be reassured by the care taken by independent regulators to protect the public," AstraZeneca's CEO said. Two major studies of vaccines against Covid-19, both paused because of potential safety concerns, are set to restart, the companies running them said Friday. “The restart of clinical trials across the world is great news as it allows us to continue our efforts to develop this vaccine to help defeat this terrible pandemic,” Pascal Soriot, AstraZeneca’s CEO, said in a statement. “We should be reassured by the care taken by independent regulators to protect the public and ensure the vaccine is safe before it is approved for use.” “We as a company have found no evidence the vaccine candidate caused the event, and we have agreed to restart the study,” Paul Stoffels, the chief scientific officer at Johnson & Johnson, said in an interview. In both cases, new documents describing potential risks for both researchers and volunteers have been prepared, and must be approved by a centralized institutional review board, one of several groups charged with protecting patients in the trial.

AstraZeneca’s restart was first reported by the Wall Street Journal; the impending restart of the J&J study was first reported by the Washington Post.  AstraZeneca stopped administering new doses of its vaccine on Sept. 6, a step first reported by STAT, after a participant in the trial developed neurological symptoms. These symptoms were reportedly caused by transverse myelitis, a serious spinal cord condition.  AstraZeneca said in its statement that the voluntary pause was part of its standard review process for safety events, and that such pauses are not unusual. It said reviews from the trial’s independent monitoring  committees indicated it was safe for the trials to resume, and that this conclusion was supported by international regulators.  A study of the vaccine in the U.K. restarted on Sept. 12, and shortly thereafter studies in Brazil and South Africa resumed. A study in Japan restarted earlier this month. But the Food and Drug Administration decided to further investigate the case, and the U.S. trial has remained on hold for more than a month.

A trial of another vaccine, being developed by Johnson & Johnson, was paused on Oct. 11.  According to a person familiar with the matter, a male volunteer in his twenties had a cerebral hemorrhage and transverse sinus venous thrombosis. The Washington Post, citing two sources, said this case was a stroke. Stoffels said that the case was reviewed by external experts, with reports made continuously both by the study’s data and safety monitoring board, an outside panel overseeing the studies, and the FDA. A final report was sent to the agency late this week. Circumstances with the patient made the process slower than it might have been. “We worked as hard as we could,” Stoffels said. “We would not put more people at risk until we knew what the cause or relationship would be.” The J&J study could begin enrolling patients again early next week, Stoffels said. He noted that the study already includes a large number of sites, and that the company will be making sure the participants are diverse in their ethnic background, their age, and any disorders they have that could make them higher risk. The J&J effort is important because it is the only one of the major vaccine efforts to be testing a single dose, and the company has made the main goal of its study to test whether the vaccine prevents severe or moderate Covid-19, not just symptomatic cases of the disease.

A large, United Kingdom-based Phase 2/3 study testing a Covid-19 vaccine being developed by AstraZeneca has been restarted, according to a statement from the company. News that the trial is resuming comes four days after the disclosure that it had been paused because of a suspected serious adverse reaction in a participant.  A spokesperson for AstraZeneca told STAT that at this point, only the trial in the U.K. has been resumed. The company is also conducting Phase 2/3 or Phase 3 trials in the U.S., Brazil, and South Africa.  “The Company will continue to work with health authorities across the world and be guided as to when other clinical trials can resume to provide the vaccine broadly, equitably and at no profit during this pandemic,” the spokesperson, Michele Meixell, wrote in an email.

Saturday’s statement from AstraZeneca said the independent U.K. investigation into the event has concluded and it advised the Medicines Health Regulatory Authority, Britain’s equivalent of the Food and Drug Administration, that it was safe to resume the trial. The MHRA concurred and gave the green light for the trial to restart. The illness that triggered the international pause, which occurred in a woman who was in the vaccine arm of the U.K. trial, has not been officially disclosed, though AstraZeneca CEO Pascal Soriot told a group of investors on Wednesday that her symptoms were consistent with transverse myelitis, a serious condition involving inflammation of the spinal cord that can cause muscle weakness, paralysis, pain and bladder problems. The AstraZeneca statement said information about the illness the woman suffered cannot be disclosed. Oxford University, where the vaccine was developed, said in a separate statement that the nature of the illness cannot be revealed “for reasons of participant confidentiality.” As part of the review process, independent boards overseeing trials of a number of other Covid-19 vaccines were analyzing their own data, looking for cases. There are at least 35 vaccines in clinical trials around the world, nine of which are in Phase 3, the final stage of testing.

It’s not uncommon for clinical trials to be paused. This is the second known hold of studies of the AstraZeneca vaccine. A woman in the U.K. trial was diagnosed with multiple sclerosis in July, but that event, which triggered the first pause, was deemed not to be related to the vaccine. An AstraZeneca spokesperson previously described the decision as a “routine action which has to happen whenever there is a potentially unexplained illness” in a trial. Still, the pause drew extraordinary attention because of the urgent need for progress on Covid-19 vaccines in the midst of the pandemic.