(Bloomberg Opinion) -- Some 71 million Americans have been vaccinated with the Moderna vaccine. The company has seen its stock price soar. But last week, Moderna announced that the U.S. Food and Drug Administration would take more time to decide whether the company’s two-dose vaccine could be used on children aged 12 to 17 after studies showed the vaccine resulted in a higher incidence of myocarditis, or inflammation of the heart, in males.
Europe approved the Moderna vaccine for use in adolescents in July. But Finland has paused use in young men; Sweden, Germany and other European countries have also announced age-related restrictions. Moderna’s stock has taken a hit, too, though part of that is related to a battle with the U.S. National Institutes of Health over patent rights.
Below, Bloomberg Opinion’s Therese Raphael speaks to Bloomberg Intelligence senior pharmaceutical analyst Sam Fazeli about the implications of the findings.
Therese Raphael: Data from France suggest the Moderna vaccine carries a greater risk of myocarditis in males between the ages of 12 and 29 than the Pfizer and BioNTech vaccine. First, what exactly is the risk being discussed? Does the public need to worry?
Sam Fazeli: The first thing to note is that these side effects are very rare and that the benefits of vaccination far outweigh these rare risks. The safety issue that is being reviewed is that of inflammation of the heart muscles (myocarditis) or the membrane around the heart (pericarditis), which can be associated with pain and discomfort and also shortness of breath and a reduced ability to conduct normal daily functions. In its most serious forms, it could lead to death, but the vast majority of the side effects seen after vaccination with mRNA vaccines has been mild.
While some patients require hospitalization, their symptoms resolve quickly. What is important to note is that myocarditis or pericarditis can also arise from a Covid-19 infection, and some data has shown that the risk is much higher following infection than after vaccination.
A French study found there were 131.6 cases of myocarditis per million doses for the Moderna vaccine compared to 26.7 per million doses for the Pfizer vaccine in males aged under 30. While the levels were lower, there is also a difference in 30 to 50 year olds: 4.7 vs. 26.5 per million doses for the Pfizer vaccine.
TR: Moderna issued a further defense of sorts on Thursday, citing Centers for Disease Control data showing rates of mild or severe Covid were lower in those who had Moderna than those with Pfizer’s or Johnson & Johnson’s vaccine. That almost seemed a diversion. How should we think about the efficacy differential here? And does that apply to the booster shot as well?
SF: There is a lot of data coming out of various real world studies that appear to suggest that the Moderna shot provides higher protection against infection than the Pfizer-BioNTech one, though the difference, if any, in terms of severe disease is much less apparent. Both vaccines are highly effective in preventing hospitalizations.
To a degree, I think the higher risk of heart inflammation with the Moderna vaccine may be the price for its higher effectiveness, and both may be related to the two following two facts. First, Moderna uses 100 micrograms of mRNA vs. 30 micrograms in each Pfizer-BioNTech shot. Second, Moderna’s shots are given with a four-week time interval between the two doses, compared to three weeks for Pfizer-BioNTech. It’s not surprising then that Moderna's vaccine induces a higher starting antibody response than Pfizer-BioNTech, which then translates to somewhat longer protection against infection. But, it carries the higher risk.
When it comes to boosters, more data is needed. It appears that a third shot of either vaccine raises antibody levels to the same high levels. In other words, the third shot may neutralize the difference in effectiveness of the two vaccines.
TR: Do we know why some young men experience myocarditis after vaccination?
SF: This is still being looked into. If it turns out that it has to do with the amount of mRNA in the vaccine, it has broader ramifications for the future vaccine hopes for both Moderna and Pfizer-BioNTech, especially as both aim to develop combination vaccines which may require high levels of mRNA material representing different infectious agents.
For example, Moderna is hoping to develop a hexavalent vaccine with four mRNA representing influenza virus, one for SARS-CoV-2 and another for respiratory syncytial virus. If each requires 20 or 30 micrograms of mRNA, the six will need a total of between 120 to 180 micrograms. This could be problematic from a “reactogenicity” perspective — which is the body’s short-term, immediate response to the vaccine — and the rate of rare side effects such as myocarditis.
TR: If the culprit is the higher dosage of mRNA in the Moderna shot, what are the implications for boosters, in which the recipient gets half the dosage of the primary series?
SF: As for boosters, data from Israel appears to suggest no further increase in the risk of myocarditis, but the country is using Pfizer-BioNTech’s shot rather than the Moderna vaccine. So we need more data for Moderna, though their lower 50 microgram booster dose appeared to cause a similar or lower level of side effects to that seen after dose two. Whether this translates into a lower risk of myocarditis — which can only be studied in large populations given the very low rates — is yet to be determined.
This column does not necessarily reflect the opinion of the editorial board or Bloomberg LP and its owners.
Therese Raphael is a columnist for Bloomberg Opinion. She was editorial page editor of the Wall Street Journal Europe.
Sam Fazeli is senior pharmaceuticals analyst for Bloomberg Intelligence and director of research for EMEA.
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