Moderna COVID-19 Vaccine Trial Results Not Strong Enough to Warrant Authorization for Children: Experts

Company says substandard results of COVID-19 vaccine trial expected

Moderna COVID-19 Vaccine Trial Results Not Strong Enough to Warrant Authorization for Children: Experts
A medical volunteer prepares a Moderna COVID-19 vaccine for a patient in Orange, Calif., on March 9, 2021. (John Fredricks/The Epoch Times)
Meiling Lee
Zachary Stieber
Regulators in the United States and elsewhere should not clear Moderna's COVID-19 vaccine for children based on a clinical trial that found the shot under 50 percent effective in preventing infection, experts say.

Moderna is pushing for emergency authorization from the U.S. Food and Drug Administration (FDA) for its jab for kids as young as 6 months of age, based on the results of the trial.

The decision to authorize would mean some 20 million of the youngest children in America could get a COVID-19 vaccine for the first time since the pandemic started.

Some parents and experts want that to happen sooner rather than later and are willing to accept less than ideal results. But others aren't convinced that most of the age group needs a vaccine, especially a shot that doesn't perform well against emerging variants.

While some children have died or gotten seriously ill from COVID-19, the disease caused by SARS-CoV-2—also known as the CCP (Chinese Communist Party) virus—their vulnerability is much smaller compared with older people, and most youth experience mild or no symptoms, according to the Centers for Disease Control and Prevention (CDC). A recently published study found T-cells, a form of protection, worked better against the virus in infant mice than in adult mice; while another concluded infants and toddlers who contract the virus have a superior immune response when compared to adults.

The very low risk of severe COVID-19 for children presents a much different risk-benefit calculus, experts say.

Particularly for children, "you've really got to show the benefits markedly outweigh any risks," Dr. Peter Collignon, an infectious diseases physician at Canberra Hospital, told The Epoch Times over Zoom.

In 5- to 11-year-olds, for instance, a British government panel determined that 2 million vaccine doses would prevent as few as 17 hospitalizations due to acute COVID-19. Amid a less severe future variant, some 4 million doses would be needed to prevent a single intensive care unit admission.
"No prospective clinical or epidemiological data that I am aware of has been provided to show that younger age groups [tested] in the Moderna study would fare any differently," Dr. David Gortler, an FDA policy oversight fellow at the Ethics and Public Policy Center who used to work for the FDA, told The Epoch Times in an email.

Does the Trial Meet Regulatory Standards?

The trial from which Moderna announced interim results is called KidCOVE. It involves two groups: children 6 months of age to under 2 years, and children 2 years of age to 5 years.
The U.S.-based company, on March 23, released a summary of interim data, announcing the trial met its endpoint, which was a certain threshold of neutralizing antibody response in both age groups after receiving a two-dose series of the vaccine.

The results were so positive that "we are working with the U.S. FDA and regulators globally to submit these data as soon as possible," Stephane Bancel, Moderna's CEO, said in a statement.

But the actual clinical impact was substandard.

During the wave driven by the Omicron virus variant, the vaccine was just 43.7 percent effective in the youngest group, and 37.5 percent effective in the other children.

Both measures are lower than the 50 percent bars established by the FDA and the World Health Organization for emergency authorization.

"That's not acceptable by the FDA's own standards," Dr. Steven Hatfill, a virologist who advised the Trump administration, told The Epoch Times.

"Our approach has always been to conduct a regulatory review that’s responsive to the urgent public health needs created by the pandemic, while adhering to our rigorous standards for safety and effectiveness. While we cannot comment on any submissions pending before the agency, we remain committed to conducting a timely and thorough evaluation of the available data and information on the use of COVID-19 vaccines in the youngest children," Alison Hunt, an FDA spokeswoman, told The Epoch Times in an email.

Moderna did not respond to requests for comment.

Rival Fails to Generate Adequate Results

Pfizer, another large vaccine maker, planned to ask the FDA for emergency clearance for young children in October 2021, but interim results from a clinical trial showed the two-dose regimen did not produce an adequate immune response in some of the children.

The U.S.-based firm and its partner, Germany's BioNTech, turned to a three-dose regimen, hoping that would prove more successful.

U.S. regulators soon solicited updates from the companies, after Omicron became the dominant variant in the country, driving a wave of COVID-19 cases and hospitalizations. The U.S. government was ready to ship millions of doses for young kids by the end of February. But just before a February meeting with its panel of expert advisers, the FDA delayed the decision, saying the data from the trial showed the vaccine did not meet the agency's standard.

"The data that we saw made us realize that we needed to see data from a third dose, as in the ongoing trial, in order to make it the determination that we could proceed with doing an authorization," Dr. Peter Marks, the official in charge of the FDA's Center for Biologics Evaluation and Research, told reporters on a call at the time.

Former FDA Commissioner Scott Gottlieb, now a Pfizer board member, said the decision stemmed from a low number of COVID-19 cases in both arms of the trial.

It remains unclear whether Pfizer's jab returned results similar to Moderna's.

A Freedom of Information Act request for documents and presentations from Pfizer and other outside parties sent to the FDA for the abruptly-canceled meeting was rejected. Officials said they had not received any such documents.

A request for FDA-produced documents was denied, with officials alleging they contained trade secrets. The Epoch Times has appealed the determination.
 A view of the Food and Drug Administration's White Oak campus in Silver Spring, Md., on Dec. 17, 2020. (Brendan Smialowski/AFP via Getty Images)
A view of the Food and Drug Administration's White Oak campus in Silver Spring, Md., on Dec. 17, 2020. (Brendan Smialowski/AFP via Getty Images)

Vaccine Effectiveness Waning

In recent months, a growing amount of data show that the Moderna and Pfizer vaccines provide little protection against infection from Omicron in all recipients 5 years and older, undermining earlier risk-benefit calculations, though the shielding against severe disease has held up better.
The FDA said in June 2020, before authorizing any vaccines, that trials supporting COVID-19 vaccines should set a primary efficacy endpoint of disease prevention or severity reduction of at least 50 percent. The World Health Organization has set the same threshold.
But the FDA later provided a loophole for companies wanting to get clearance for children. The agency said vaccine effectiveness in children "may be inferred" through immunobridging, a technique that compares an immune response in pediatric recipients to the immune response triggered in older age groups "for which effectiveness of the vaccine has already been demonstrated."

"Our trial actually was powered on immunobridging," Jacqueline Miller, a senior vice president at Moderna, told investors in a recent call. "The idea was to infer effectiveness."

"At the end of the day, that's the objective we've been asked to meet by regulators, and we committed ourselves to meet, which is, can we demonstrate a dose of the vaccine that provides the same benefit to children, in this case under the age of 6, that is provided to older adults," added Stephen Hoge, Moderna's president.

Moderna executives say the less than ideal efficacy against infection was expected since the vaccine does poorly in shielding against the virus in adults.

That theme was picked up by some other experts, including Dr. Anthony Fauci, the longtime head of the National Institute of Allergy and Infectious Diseases.

The average efficacy "may seem like a low number, but in the era of Omicron this is actually quite comparable to the efficacy against infection in what we’re seeing now with other vaccines,” he said during a recent briefing.

The interim trial results did not include an estimate of effectiveness against severe disease or hospitalization, because no severe COVID-19 was observed in the vaccinated or unvaccinated cohorts.

Executives claimed that efficacy against severe disease could be assumed.

"We believe the benefit that we've been able to demonstrate scientifically here—with immunogenicity and even efficacy that is consistent with adults—gives us every reason to believe there will be an ability to extend that to severe disease, hospitalization—all the outcomes that we desperately want to prevent—which although much rarer in children, and therefore harder to observe in a clinical trial, do in fact happen," Hoge said.

Low Uptake Among Kids Prompts Caution

On a recent call with reporters, Marks, the FDA official, said that he is pestered by family members regularly about vaccines for the youngest children.

"We at FDA really understand the urgency that people feel about wanting to get the youngest children vaccinated. We also understand that this is the age range when people are most concerned about potential side effects and potential safety of vaccines. And we know that in this population, we have to do our job extremely well to make sure that we ensure that there is very good evaluation of the safety and effectiveness, so that when we make our recommendation, people will trust that recommendation ... [and] parents will pick up and go vaccinate their children," he said.

Lagging vaccination rates among the 5- to 11-year-olds emphasize the need to make sure a vaccine is properly evaluated before being cleared for the younger kids, Marks said.

Just 35 percent of children in that age group have gotten at least one dose of a COVID-19 vaccine since it was cleared in the fall of 2021.

Surveys indicate parental concerns include potential long-term side effects.

Regulators plan to consult the Vaccines and Related Biological Products Advisory Committee, a panel of outside experts, before making a decision. They have increasingly bypassed the panel during the pandemic, including when authorizing fourth shots for many Americans, after members pushed back against a government effort to pre-clear boosters for all American adults.

Dr. William Schaffner, an infectious diseases professor at Vanderbilt University Medical Center, said he thought the Moderna results would be received "with favor" by the panel.

"There will be the notion that, as with older populations, the effectiveness of the vaccine will be better against severe disease than relatively minor infections," Schaffner, a liaison for the Centers for Disease Control and Prevention's advisory panel, told The Epoch Times.

Still, Schaffner was among the experts hesitant to make a judgment about whether the vaccine was effective enough to warrant clearance. They said they wanted to see more data first.

Other experts were adamant that regulators should not assume adequate efficacy against severe disease.

"The problem with those presumptions is they may be correct, but they're presumptions. And children do not behave the same way as adults with vaccines. So to actually license a vaccine for millions and millions of children based on a pretty small study, and on a presumption that children will behave the same as adults, I think is not doing science properly and not doing the regulatory approach properly," Collignon, the Australian expert, said, urging further trials to focus on clinical outcomes, particularly hospitalization and death, rather than measures like a certain level of neutralizing antibodies.

Safety Concerns and Natural Immunity

Moderna said its trial did not show any "new safety concerns." That wording alarmed some experts.
That "does not address existing safety concerns," said Gortler, the former FDA medical officer.
Post-vaccination heart inflammation has been detected at higher than expected rates in many pediatric age groups. A recent case study of 16 adolescents ages 12 to 17 diagnosed with the inflammation after a second dose of Pfizer's vaccine found that despite the patients showing clinical improvement, many still had persistent cardiac MRI findings three to eight months later, “raising concerns for potential longer-term effects.”

Moderna vaccine recipients are at higher risk of post-vaccination heart inflammation, according to the CDC's safety surveillance.

Other side effects from the Moderna and Pfizer vaccines, both built on messenger RNA, have also been detected.

Vaccine supporters say the benefits, primarily the prevention of severe disease, outweigh the risks, but that cannot be said about the shots for young children at this time.

Long-term issues could crop up, as with various vaccines over the years. The H1N1 flu vaccine, for instance, was shown to cause an increased risk of narcolepsy among children.

"We don't know the long-term effects of any of these vaccines. We know that it does disturb natural immunity," said Hatfill, the virologist, referring to studies that indicate people with natural immunity are more prone to side effects and re-infection after getting a vaccine.

Another concern is the continued lack of incorporation of infection-induced immunity, also known as natural immunity, by federal agencies in the United States and many other countries, despite a growing effort to get regulators to recognize it.
A majority of American youth have recovered from COVID-19, giving them strong protection from severe disease if they contract the CCP virus, according to serology data.
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