Cases of myocarditis following a COVID-19 vaccine are rare, usually mild, and tend to resolve quickly — unlike myocarditis and other complications arising from the virus itself, according to an expert participating in a discussion on mRNA vaccines and cardiovascular (CV) health Saturday at the 2021 American Heart Association (AHA) Scientific Sessions.
Biykem Bozkurt, MD, PhD, FAHA, Baylor College of Medicine cardiologist and heart failure specialist, provided an overview of myocarditis data before the AHA session turned to experts at Pfizer and Moderna, the 2 companies that have developed and distributed mRNA vaccines worldwide. The companies are the largest producers of COVID-19 vaccine in the United States, where 439 million doses have been distributed.
Mikhael Dolsten, MD, PhD, Chief Scientific Officer and President, Worldwide Research, Development and Medical for Pfizer, first discussed the “end-to-end” approach the company has taken with COVID-19 by being the first to develop a vaccine. to the US market and then target a therapy to dramatically reduce the risk of hospitalization or death.
“The comprehensive approach was … that vaccine will be crucial to get the pandemic under control,” Dolsten said. “But our experience is also that when you supplement the vaccine with a drug, you get the maximum chance of medical management.”
Next, Stéphane Bancel, MBA, CEO of Moderna, discussed how the company’s focus on mRNA since 2011 has not only paid off with a COVID-19 vaccine, but will also revolutionize vaccine and therapeutic innovation. The company now has dozens of vaccines in development. “What’s very fundamental about mRNA is that it’s an information molecule,” he said. “It just changes how you can do things in terms of speed.”
Because the same chemical components are used to make the mRNA from vaccine to vaccine, time to market should increase and the failure rate in drug development could decrease, Bancel said.
Data on myocarditis. Bozkurt explained that myocarditis, an inflammation of the middle heart wall, has been seen in small numbers with other vaccines, but is also seen in the general population — about 20 cases per 100,000 people occur each year, she said.
Because vaccine-related cases are more concentrated among young men — late teens and young adults — alarms have been raised about vaccine safety in this group. But Bozkurt said the overall incidence of myocarditis — even before COVID-19 — was more common in this group; researchers believe the higher numbers may be related to testosterone, and Bozkurt said there is a need to research genetics, which puts some at greater risk.
Still, the incidence of myocarditis is uncommon. Multiple datasets, including registry data from Israel and data from the Ministry of Defense (DOD) tracking vaccine responses in the military, show that the overall incidence of myocarditis after vaccination is about 1 per 100,000 people; but the percentage is higher in young men. DOD reported that 23 men developed myocarditis after 2.8 million doses were administered, Bozkurt said. An analysis of cases from Israel published in the New England Journal of Medicineearlier this fall, the rate among older male teens (ages 16-19) was 1 case per 6,637 male recipients.
However, she said the cases arising from a vaccine are rarer and milder than those arising from the development of COVID-19 itself.
“There were other cardiovascular complications associated with the infection itself, including DVT, myocardial infarction, intracranial hemorrhage, pulmonary embolism, which far exceeded the myocarditis risk seen with mRNA vaccination,” Bozkurt said. “The risk of myocarditis due to COVID-19 infection is also further confirmed by the CDC data showing that the overall risk of myocarditis with the infection itself is 16 times higher in the general population and in children under 16 years of age. of myocarditis with COVID infection is 37 times higher, underscoring the need for us to recognize that the risk is significantly higher with the infection itself.”
When myocarditis was present after a COVID-19 vaccine, she said, some patients had chest pain and EKG and cardiac troponin levels were typically abnormal. “Symptoms and findings resolved within a few days and the benefits of vaccinations significantly outweigh the risk,” she said.
Pfizer’s “comprehensive” approach. Even for a massive pharmaceutical company like Pfizer, it’s no small feat to deliver 3 billion COVID-19 vaccine doses worldwide by the end of 2021 while working on an oral drug that has delivered Phase 2/3 interim results.
“What does this mean?” said Dolsten. “As we generate that encouraging early clinical data, we simultaneously ran the risk of investing thousands of scientists and of course the funds to prepare for potential success by deploying our large manufacturing and pharmaceutical site network…”
But, said Dolsten, that was not the end. Pfizer leveraged its decades of vaccine experience to think “far outside” the FDA emergency use authorization. “For example, we were working with real-world evidence from Israel that we heard recently [as well as] a multi-stage program after initial authorization for emergency use, followed by full approval,” he said, “increases confidence, but added scrutiny.
From the beginning, he said, Pfizer has studied the durability of the vaccines and was able to demonstrate the need and value of a booster injection through real-world evidence. Pfizer then conducted a randomized, controlled trial on booster shots, using a sample of the population that had been the first phase of the original vaccine study. “Again, [this] showed very favorable payout percentages,” said Dolsten.
Today, the World Health Organization estimates that up to 25% of the 28.5 million doses administered daily are boosters. This is not without controversy, as WHO officials say boosters are being distributed in rich countries, while many poor countries are still unable to give everyone a starting dose.
Still, Dolsten said, the process of moving through the population from the oldest adults to the middle-aged, to younger adults and eventually the 12-17 and 5-11 age groups “was a creative approach that I’m really good at.” feel.”
Having oral therapy is just as important. “There will be individuals who are not vaccinated or individuals who do not receive the maximum vaccination because they are immunocompromised,” he said. “I hope that gave you a little bit of a sense of what really was our comprehensive and intended approach. And it is still being rolled out with science and data.”
Moderna’s plans beyond COVID-19. The success of its COVID-19 vaccine has put Moderna on the map – AHA President Nancy Brown noted that before the pandemic, Moderna was not a household name, but that has changed.
Bancel said it is important to understand the versatility of mRNA technology and the possibilities it offers for both infectious and chronic diseases. The company has already announced it has dosed its first participant in a phase 3 trial for a cytomegalovirus (CMV) vaccine. “As you know, this has been the top priority of the National Academy of Medicine for vaccines for 20 years, and major vaccine companies have not been able to make such a vaccine because it is a very complex herpes family virus.”
He touted the second phase to be presented by AstraZeneca at AHA, involving a vaccine for the heart of those who have had a heart attack. “That mRNA coding is for human VEGF. And the idea here is to boost the vascularization of a heart muscle afterwards,” he said. A phase 1 trial showed that the approach was well tolerated, he said.
The company is envisioning a “pan-respiratory” vaccine, with the expectation that COVID-19 will become “endemic” and that in addition to a flu shot, people will need an annual COVID shot. But the good news is that the new technology being developed to fight COVID-19 will lead to better vaccines for strains of flu. “So one shot and you’re ready for winter,” Bancel said.
Borzkut circled back with Bancel, asking if the company would partner with AHA or other organizations to adapt the vaccine and address the ongoing problems of myocarditis, as uncommon as they are.
“I would say we would be very interested,” Bancel said. “As you know, all we do at Moderna is mRNA. And we are very curious to always go to mechanistic understanding, because as you say, not only does it allow us to potentially tweak this product, if we find out what causes the perception, even if it is very rare. It will help us because we will not only have a product in the vaccine field, but also in the therapeutic field.”
Mevorach D, Anis E, Cedar N, et al. Myocarditis after BNT162b2 mRNA vaccine against COVID-19 in Israel. N Engl J Med. Published online Oct 6, 2021. doi: 10.1056/NEJMoa2109730