The Food and Drug Administration is telling Pfizer and Moderna to expand the warning labels on their COVID-19 vaccines about the risk of a possible heart injury side effect linked to the mRNA shots, primarily in teen boys and young men, citing findings from a study published last year and new agency data.

Orders to expand the warnings were posted Wednesday by the FDA, in letters dated April 17 to Pfizer and BioNTech about their Comirnaty vaccine and Moderna about its Spikevax vaccine.

Both vaccines previously carried warnings about how the risk of the heart side effects — which doctors call myocarditis (an inflammation of the heart muscle) and pericarditis (inflammation of the membrane surrounding the heart) — looked to be higher in young men, generally within the first week after vaccination. While the earlier labels specified ages 18 to 24 years old for Moderna’s vaccine and 12 to 17 years old for Pfizer’s, the new warning will apply to males ages 16 to 25 for both vaccines.

“Following administration of the 2023-2024 Formula of mRNA COVID-19 vaccines, the highest estimated incidence of myocarditis and/or pericarditis was in males 16 through 25 years of age,” the FDA says in the new blanket warning it will require for both vaccines.

The rate of myocarditis and pericarditis was around 8 cases per million doses for children and adults under 65 years old after use of that season’s vaccines, the FDA says.

The new warnings ordered by the FDA add that the “highest estimated incidence was in males 16 through 25 years of age,” with a rate of 38 cases per million.

The Centers for Disease Control and Prevention has previously described rates of myocarditis and pericarditis as rare after COVID-19 vaccination. 

CDC officials told the agency’s vaccine advisers last month that acute myocarditis “tends to resolve quickly” after vaccination, and no increased risk had been seen in data from recent seasons in people 12 to 39 years old.

It is unclear whether Pfizer or Moderna disputed the order. They had “within 30 calendar days of the date of this letter” to try to rebut the demand. Spokespeople for Moderna and Pfizer did not immediately respond to a request for comment.

“Americans deserve radical transparency around the safety and efficacy of COVID vaccines and the FDA is delivering on their promise to do just that. Spikevax and Comirnaty should take steps to ensure that individuals are aware of COVID vaccine-related adverse events resulting in myocarditis and pericarditis,” Andrew Nixon, a spokesperson for the Department of Health and Human Services, told CBS News in an email. Nixon did not explain why the letters were posted more than a month after they were written.

They appeared on the FDA’s website hours ahead of a hearing organized by the Republican-led Senate Homeland Security and Governmental Affairs Committee on “how health officials downplayed and hid myocarditis and other adverse events associated with the COVID-19 vaccines.”

Aaron Siri, an attorney who worked closely with Health and Human Services Secretary Robert F. Kennedy Jr. in the past to call on the FDA to pull COVID-19 and other vaccines and vet nominees during the transition, is among the witnesses.

The FDA says the warnings were spurred by new data from the agency’s safety surveillance system and results published in October from scientists following up with people who developed COVID-19 vaccine-associated myocarditis.

Talks about this kind of safety labeling change began before the ouster of the FDA’s previous top vaccines official, Dr. Peter Marks, multiple people familiar with the situation said, but had not yet been finalized as officials wrestled with how to accurately present the findings. Marks left the FDA on April 5.

Scientists in that study followed up with people who had faced chest pain and elevated amounts of troponin in their blood, a protein that usually signals some kind of heart damage. They were predominantly young adolescent males.

“While their clinical course was nearly always mild with a low prevalence and extent of cardiac dysfunction, myocardial injury was common,” the scientists wrote in the study, which was co-authored by FDA officials.

Similar to what the study described, the FDA’s new warning also says that the heart MRI findings showed “improvement over time in most people.”

“It is not known if these heart MRI findings might predict long-term heart effects of myocarditis. Studies are underway to find out if there are long-term heart effects in people who have had myocarditis after receiving an mRNA COVID-19 vaccine,” the FDA said.

The Food and Drug Administration says it has decided to continue approving COVID-19 vaccine updates for seniors and others at higher risk of severe disease, but will require vaccine makers to conduct major new clinical trials before approving them for wider use. The decision means many Americans without underlying conditions may not have access to updated shots.

“The FDA will approve vaccines for high-risk persons and, at the same time, demand robust, gold-standard data on persons at low risk,” the agency said in an article published by The New England Journal of Medicine, authored by FDA Commissioner Dr. Martin Makary and his new top vaccines official, Dr. Vinay Prasad.

Vaccine manufacturers will need to conduct “randomized, placebo-controlled trials” before the FDA will approve future applications to give shots to “all healthy persons” between the ages of 6 months and 64 years old, they wrote. 

Otherwise, companies will only be able to get their routine COVID-19 vaccine updates approved for seniors as well as people with an underlying medical condition that increases the risk of severe disease, like pregnancy or diabetes.

“The range of diseases in the CDC definition of high risk of severe disease is vast, including obesity and even mental health conditions such as depression. Estimates suggest that 100 million to 200 million Americans will have access to vaccines in this manner,” they wrote.

Makary and Prasad criticized the U.S. for adopting “a one-size-fits-all regulatory framework” to grant broad authorization for past COVID-19 vaccine boosters in the past, and cited poor uptake of past annual COVID-19 booster shots. 

They also pointed to other developed countries that have already limited annual COVID-19 vaccine boosters to only older adults and those with underlying conditions that increase their risk of severe disease.

“The U.S. policy has sometimes been justified by arguing that the American people are not sophisticated enough to understand age- and risk-based recommendations. We reject this view,” they wrote. 

The new “regulatory framework for COVID-19 vaccination” laid out by the FDA’s new leadership under Health and Human Services Secretary Robert F. Kennedy Jr. comes ahead of a key meeting of the agency’s outside vaccine advisers this Thursday, to decide on how to update the strain used in next season’s shots. 

In recent years, the FDA has greenlighted those updates in a process similar to the annual flu shots, based largely on laboratory data showing the vaccines can trigger antibody levels similar to previously approved shots. 

That is a lower bar than requiring brand new randomized trials of the vaccines tested against a placebo to show it prevents symptomatic disease — a process which is usually only required for new shots when there is no currently approved immunization available. 

But Makary and Prasad said COVID-19 shots should be held to a different standard, citing differences in how the virus mutates and the immunity offered by vaccines and previous infection. 

“Ultimately, these studies alone can provide reassurance that the American repeat-boosters-in-perpetuity strategy is evidence-based,” they wrote.

It is unclear whether and when vaccine makers would be able to conduct these kinds of trials, if they wanted to try again for a broader approval from the FDA. Makary and Prasad floated the possibility of trials as soon as the coming months.

“Covid-19 has summer transmission that can facilitate the conduct of randomized studies that continue to apply in future time periods,” they wrote. 

Spokespeople for vaccine manufacturers Pfizer and Moderna did not immediately respond to a request for comment. A Novavax spokesperson declined to comment.

Novavax earned a narrow FDA approval over the weekend for its COVID-19 vaccine, which was limited to seniors as well as adults and adolescents with at least one underlying condition.

While U.S. health care providers are usually allowed to administer vaccines with FDA approval “off-label” outside the limits laid out by the agency, a narrower approval can affect access and limit insurance coverage for the vaccinations. 

It comes as the Centers for Disease Control and Prevention has also been weighing narrowed recommendations for the shots.

The CDC’s recommendations directly impact which vaccinations health insurers are required to cover under the law. 

The head of the Food and Drug Administration said Tuesday that the agency is now looking at whether it will still approve COVID-19 vaccines for next winter, citing a lack of data on booster shots.

“We’re taking a look. I can’t comment on any particular application. As you know, we have a bunch of applications for those booster shots,” FDA Commissioner Dr. Marty Makary told CBS News chief Washington correspondent Major Garrett.

Makary said many health care workers did not get the last round of COVID-19 vaccine booster shots, calling it “a bit of a public trust problem.”

“I think there’s a void of data. And I think rather than allow that void to be filled with opinions, I’d like to see some good data,” Makary said.

His answer marks a change from during the Biden administration, when FDA officials backed plans to routinely update the COVID-19 vaccines each year.

Last year, the FDA issued guidance on what strain should be targeted by the shots for the following winter. Updates to Moderna and Pfizer’s COVID shots for the new strain were approved in August.

The Centers for Disease Control and Prevention is also now weighing whether to significantly narrow its recommendations for COVID-19 vaccines.

Makary’s remarks echo his justification for delaying Novavax’s COVID-19 vaccine, which was expected to get full approval on April 1. Novavax said Monday that the FDA had asked the company to commit to another clinical trial of the shot.

“Today, there is broad population immunity, and the big question is does it provide a benefit? Without a study on the new formulation and product, we can’t give an honest evidence-based answer to that question,” Makary told the newsletter “Inside Medicine” this week.

Multiple companies are now also being asked “to do clinical studies, a basic clinical study, so we can educate the population and have information to work with,” Makary told CBS News.

“It’s my general feeling, not with this particular product, which I can’t discuss in depth, but with drugs in general, that we need to know if they work today in order to be able to recommend them,” he said. 

He also praised his special assistant, Dr. Tracy Beth Høeg, when asked what role she played in the agency’s evaluation of Novavax’s application. 

“Dr. Høeg is an amazing M.D.-Ph.D. who has joined my staff as a special assistant to the commissioner. And she is involved in reviewing data sets at the agency. And I’m really excited to have her in the process,” Makary said.

Trade industry publication The Pink Sheet previously reported that Høeg had been asked to step in on Novavax’s application. Høeg was also added to the CDC’s Advisory Committee on Immunizations, in a slot previously filled by a career vaccines official from the FDA.

Former FDA officials have criticized the agency’s new political leadership for their intervention in vaccine approvals, a process which is usually entrusted to career scientific officials.

In a commentary published this week, former officials Phil Krause and Luciana Borio called on the FDA to “stick to its normal processes.”

“Shifting standards and late-stage demands for new data — based on faulty scientific assumptions — erode trust, delay access to important tools, and discourage developers from advancing vaccine innovation,” they wrote.