UK issues anaphylaxis warning on Pfizer vaccine after adverse reactions

https://www.reuters.com/article/health-coronavirus-britain-vaccine/update-5-uk-to-refine-allergy-warning-on-pfizer-vaccine-sparked-by-two-adverse-reactions-idUSL8N2IP307

UK issues anaphylaxis warning on Pfizer vaccine after adverse reactions -  YouTube

Britain’s medicine regulator said anyone with a history of anaphylaxis to a medicine or food should not get the Pfizer-BioNTech COVID-19 vaccine, giving fuller guidance on an earlier allergy warning about the shot.

Starting with the elderly and frontline workers, Britain began mass vaccinating its population on Tuesday, part of a global drive that poses one of the biggest logistical challenges in peacetime history.

The Medicines and Healthcare Products Regulatory Agency (MHRA) said there had been two reports of anaphylaxis and one report of a possible allergic reaction since rollout began.

“Any person with a history of anaphylaxis to a vaccine, medicine or food should not receive the Pfizer BioNTech vaccine,” MHRA Chief Executive June Raine said in a statement.

“Most people will not get anaphylaxis and the benefits in protecting people against COVID-19 outweigh the risks… You can be completely confident that this vaccine has met the MHRA’s robust standards of safety, quality and effectiveness.”

Anaphylaxis is an overreaction of the body’s immune system, which the National Health Service describes as severe and sometimes life-threatening.

The fuller guidance, clarifying that the main risk was from anaphylaxis specifically, was issued after consulting experts on allergies. The MHRA had initially advised anyone with a history of a “significant allergic reaction” not to take the shot.

Pfizer and BioNTech said they were supporting the MHRA’s investigation.

Last week, Britain’s MHRA became the first in the world to approve the vaccine, developed by Germany’s BioNTech and Pfizer, while the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) continue to assess the data.

A top U.S. official said on Wednesday that Americans with known severe allergic reactions may not be candidates for Pfizer’s COVID-19 vaccine until more was understood about what had happened.

Canada’s health ministry said it would look at the reported adverse reactions in Britain, but said adverse events were to be expected and would not necessarily change the risk/benefit of the shot, after the country approved the vaccine.

ALLERGIC REACTION

MHRA chief Raine told lawmakers such allergic reactions had not been a feature of the Pfizer’s clinical trials.

Pfizer has said people with a history of severe adverse allergic reactions to vaccines or the candidate’s ingredients were excluded from their late stage trials, which is reflected in the MHRA’s emergency approval protocol.

However, the allergic reactions may have been caused by a component of Pfizer’s vaccine called polyethylene glycol, or PEG, which helps stabilise the shot and is not in other types of vaccines.

Imperial College London’s Paul Turner, an expert in allergy and immunology, who has been advising the MHRA on their revised guidance, told Reuters: “As we’ve had more information through, the initial concern that maybe it affects everyone with allergies is not true.”

“The ingredients like PEG which we think might be responsible for the reactions are not related to things which can cause food allergy. Likewise, people with a known allergy to just one medicine should not be at risk,” Turner told Reuters.

The EMA said in an email that all quality, safety and efficacy data would be taken into account in assessing the vaccine, including data generated outside the EU.

In the United States, the FDA released documents on Tuesday in preparation for an advisory committee meeting on Thursday, saying the Pfizer vaccine’s efficacy and safety data met its expectations for authorization.

The briefing documents said 0.63% of people in the vaccine group and 0.51% in the placebo group reported possible allergic reactions in trials, which Peter Openshaw, professor of experimental medicine at Imperial College London, said was a very small number.

“The fact that we know so soon about these two allergic reactions and that the regulator has acted on this to issue precautionary advice shows that this monitoring system is working well,” he said.

However, Gregory Poland, a virologist and vaccine researcher with the Mayo Clinic in Rochester, Minnesota, said that the MHRA and NHS had overreacted initially.

“I would not have broadened to the degree they did,” he said.

“It’s reasonable to let the world know about this, and to be aware of it in terms of people who have had reactions like this to vaccines. I think to say medicines, foods or any other allergies is past the boundary of science.”

Demand for COVID Vaccines Expected to Get Heated — And Fast

Americans have made no secret of their skepticism of COVID-19 vaccines this year, with fears of political interference and a “warp speed” timeline blunting confidence in the shots. As recently as September, nearly half of U.S. adults said they didn’t intend to be inoculated.

But with two promising vaccines primed for release, likely within weeks, experts in ethics and immunization behavior say they expect attitudes to shift quickly from widespread hesitancy to urgent, even heated demand.

“People talk about the anti-vaccine people being able to kind of squelch uptake. I don’t see that happening,” Dr. Paul Offit, a vaccinologist with Children’s Hospital of Philadelphia, told viewers of a recent JAMA Network webinar. “This, to me, is more like the Beanie Baby phenomenon. The attractiveness of a limited edition.”

Reports that vaccines produced by drugmakers Pfizer and BioNTech and Moderna appear to be safe and effective, along with the deliberate emphasis on science-based guidance from the incoming Biden administration, are likely to reverse uncertainty in a big way, said Arthur Caplan, director of the division of medical ethics at New York University School of Medicine.

“I think that’s going to flip the trust issue,” he said.

The shift is already apparent. A new poll by the Pew Research Center found that by the end of November 60% of Americans said they would get a vaccine for the coronavirus. This month, even as a federal advisory group met to hash out guidelines for vaccine distribution, a long list of advocacy groups — from those representing home-based health workers and community health centers to patients with kidney disease — were lobbying state and federal officials in hopes their constituents would be prioritized for the first scarce doses.

“As we get closer to the vaccine being a reality, there’s a lot of jockeying, to be sure,” said Katie Smith Sloan, chief executive of LeadingAge, a nonprofit organization pushing for staff and patients at long-term care centers to be included in the highest-priority category.

Certainly, some consumers remain wary, said Rupali Limaye, a social and behavioral health scientist at the Johns Hopkins Bloomberg School of Public Health. Fears that drugmakers and regulators might cut corners to speed a vaccine linger, even as details of the trials become public and the review process is made more transparent. Some health care workers, who are at the front of the line for the shots, are not eager to go first.

“There will be people who will say, ‘I will wait a little bit more for safety data,” Limaye said.

But those doubts likely will recede once the vaccines are approved for use and begin to circulate broadly, said Offit, who sits on the FDA advisory panel set to review the requests for emergency authorization Pfizer and Moderna have submitted.

He predicted demand for the COVID vaccines could rival the clamor that occurred in 2004, when production problems caused a severe shortage of flu shots just as influenza season began. That led to long lines, rationed doses and ethical debates over distribution.

“That was a highly desired vaccine,” Offit said. “I think in many ways that might happen here.”

Initially, vaccine supplies will be tight, with federal officials planning to ship 6.4 million doses within 24 hours of FDA authorization and up to 40 million doses by the end of the year. The CDC panel recommended that the first shots go to the 21 million health care workers in the U.S. and 3 million nursing home staff and residents, before being rolled out to other groups based on a hierarchy of risk factors.

Even before any vaccine is available, some people are trying to boost their chances of access, said Dr. Allison Kempe, a professor of pediatrics at the University of Colorado School of Medicine and expert in vaccine dissemination. “People have called me and said, ‘How can I get the vaccine?’” she said. “I think that not everyone will be happy to wait, that’s for sure. I don’t think there will be rioting in the streets, but there may be pressure brought to bear.”

That likely will include emotional debates over how, when and to whom next doses should be distributed, said Caplan. Under the CDC recommendations, vulnerable groups next in line include 87 million workers whose jobs are deemed “essential” — a broad and ill-defined category — as well as 53 million adults age 65 and older.

“We’re going to have some fights about high-risk groups,” said Caplan of NYU.

The conversations will be complicated. Should prisoners, who have little control over their COVID exposure, get vaccine priority? How about professional sports teams, whose performance could bolster society’s overall morale? And what about residents of facilities providing care for people with intellectual and developmental disabilities, who are three times more likely to die from COVID-19 than the general population?

Control over vaccination allocation rests with the states, so that’s where the biggest conflicts will occur, Caplan said. “It’s a short fight, I hope, in the sense in which it gets done in a few months, but I think it will be pretty vocal.”

Once vaccine supplies become more plentiful, perhaps by May or June, another consideration is sure to boost demand: requirements for proof of COVID vaccination for work and travel.

“It’s inevitable that you’re going to see immunity passports or that you’re required to show a certificate on the train, airplane, bus or subway,” Caplan predicted. “Probably also to enter certain hospitals, probably to enter certain restaurants and government facilities.”

But with a grueling winter surge ahead, and new predictions that COVID-19 will fell as many as 450,000 Americans by February, the tragic reality of the disease will no doubt fuel ample demand for vaccination.

“People now know someone who has gotten COVID, who has been hospitalized or has unfortunately died,” Limaye said.

“We’re all seeing this now,” said Kempe. “Even deniers are beginning to see what this illness can do.”

What makes a Bad Vaccine?

A Covid-19 vaccine, amazingly, is close. Why am I so worried?

A mere six months after identifying the SARS-CoV-2 virus as the cause of Covid-19, scientists are on the precipice of a having a vaccine to fight it. Moderna and the National Institutes of Health recently announced the start of a Phase 3 clinical trial, joining several others in a constructive rivalry that could save millions of lives.

It’s a truly impressive a feat and a testament to the power of basic and applied medical sciences. Under normal circumstances, vaccine approvals are measured in decades. Milestones that once took months or years have been achieved in days or weeks. If these efforts are successful, the Covid-19 vaccine could take a place alongside the Apollo missions as one of history’s greatest scientific achievements.

I’m optimistic. And yet, as someone who studies drug development, I want to temper expectations with a dose of realism and perhaps a bit of angst. Behind the proud declarations, many science and medical professionals have been whispering concerns. These whispers have escalated into a murmur. It’s time to cry them loudly:

Hey, Food and Drug Administration: Don’t be rash! Premature approval of a sub-standard Covid-19 vaccine could have dire implications, and not just for this pandemic. It could harm public health for years, if not generations, to come.

Unfortunately, elements now in place make such a disastrous outcome not only possible but in fact quite likely. Specifically, the FDA and its staff of chronically overworked and underappreciated regulators will face enormous public and political pressure to approve a vaccine. Whether or not one worries about an “October surprise” aimed at the upcoming election, regulators will be pressed hard. Some will stand firm. Some may resign in protest. But others could break and allow a bad vaccine to be released.

What makes a “bad vaccine”? Insufficient protection against the disease it is designed for, unwanted side effects, or some combination of the two. If an approved Covid-19 vaccine turns out to be ineffective, this could unintentionally promote wider spread of the disease by individuals who presume they were protected from it. Likewise, a negative experience with one vaccine might discourage the use of other vaccines that are far more safe and effective, whether they are for Covid-19 or other vaccine-preventable diseases.

Some things take time. Under normal circumstances, ensuring that a vaccine’s effects are safe and durable requires years of study and monitoring. And there is some evidence that natural immune responses to SARS-CoV-2 infection could be transient, making sustained investigation all the more necessary. A merely short-term effect could encourage vaccinated individuals to resume risky behaviors, which would all but guarantee that the epidemic endures. And if unintended side effects turn out to include, for instance, chronic inflammatory or autoimmune disease, a bad vaccine could impart lifelong damage.

But wait, there’s worse! A bad Covid-19 vaccine could further undermine confidence in the many safe, reliable vaccines already in our public health arsenal. Vaccine skepticism and anti-science bias, propagated by B-list celebrities and Russian troll farms, have been gaining strength all year. Combined with disappointing Covid-19 outcomes, such malign forces could facilitate the reemergence of once-vanquished foes — polio, measles, mumps, rubella, diphtheria, whooping cough, and tetanus — that once killed multitudes of children each year.

These are enormous risks. Placing all of our bets on a small set of untried vaccine technologies would be gobsmackingly foolish. Yet this is exactly what we are now doing. Most of the high-profile names capturing headlines are pursuing comparatively minor variations on a theme of genetic vaccines (those delivered via DNA or RNA). If one approach happens to work, the odds are higher the others will work as well. Disappointing results from one candidate, though, might presage failure across the board.

Rather than investing in a balanced portfolio of vaccines with different approaches — not to mention different therapies, devices, and diagnostics for treating Covid-19 — too many observers, too many companies, and too many governmental officials seem to be narrowly focused on hopes for a “savior” vaccine. Were that savior to fail, our national morale, already low, could plummet even further.

Don’t get me wrong. I, along with millions of Americans, want a Covid-19 vaccine. But we deserve one that’s been proven to be safe and effective.

It’s not too late to take a deep breath and devise a strategy to balance short- and long-term goals, including vaccination, improved diagnostics, and existing and novel treatments. We must support the FDA and hope that its scientists and physicians retain the strength and conviction to resist approving a substandard vaccine.

For encouragement, we should look to Frances Oldham Kelsey, a veritable patron saint of the FDA. In 1960, during her first month working for the agency, Kelsey was asked to approve a sedative called Kevadon, which had the potential to generate billions in revenue. Despite enormous pressure, Kelsey spotted a risk for toxicity and dug in her heels. She refused to rubber stamp the approval. Her actions saved the lives of countless babies. Kevadon, better known as thalidomide, proved to be one of the most dangerous and disfiguring drugs in history.

Kelsey passed away in 2015 at the age of 101. We must pray that her spirit inspires a new generation of FDA leaders with the courage to say, “No.”