A second COVID-19 vaccine was recommended for emergency use Thursday, making Moderna the latest company to produce a defense against a pandemic which has infected more than 17 million Americans.
MRNA-1273 showed 94.1% vaccine efficacy in a phase 3 trial of more than 30,000 people — where 185 placebo recipients and only 11 vaccine recipients got COVID-19.
A vigorous discussion right before the unanimous vote with one abstention focused on whether the public would misconstrue this vote as full vaccine approval instead of what it really is: emergency use authorization, which allows for an unlicensed, but still heavily reviewed, medical product to be used during a public health crisis.
The members were asked to vote on, “Based on the totality of scientific evidence available, do the benefits of the Moderna COVID-19 vaccine outweigh its risks for use in individuals 18 years of age and older?”
“The question is never ‘when do you know everything,’ it’s ‘when do you know enough,’ ” said Dr. Paul Offit, director of the Vaccine Education Center and attending physician in the Division of Infectious Diseases at Children’s Hospital of Philadelphia and voting member of the Vaccines and Related Biological Products Advisory Committee. “The answer to this question as far as I’m concerned is, I completely agree, clearly yes.”
The FDA is expected to accept the committee’s recommendation almost immediately.
The CDC’s Advisory Committee on Immunization Practices will also meet this weekend to recommend how Moderna’s vaccine should be used in the United States. Once its recommendation is accepted, more vaccine doses will begin their journeys toward front-line health care workers and long-term care residents.
Pfizer and BioNTech’s vaccine is already being distributed across the country.
Allergic reaction concerns
Numerous questions were raised Thursday about anaphylaxis — as officials noted that a female health care worker in Alaska experienced shortness of breath, an elevated heart rate and a rash 10 minutes after receiving Pfizer’s vaccine on Wednesday. Another worker in the same hospital experienced puffy eyes, lightheadedness and a scratchy throat 10 minutes after his vaccine. Two other severe reactions were reported in the U.K. last week.
Adverse reactions to vaccines are not uncommon following large vaccine rollouts and both Pfizer and Moderna said they will continue to study this issue, while the FDA and CDC will continue to closely follow participants through the nation’s vaccine monitoring systems.
Both U.S. patients required emergency intervention but are now recovering.
“The established safety surveillance systems worked exactly as designed,” said Doran Fink, deputy director-clinical, Division of Vaccines and Related Products Applications at the FDA. “While the totality of data continue to support Pfizer’s use under an emergency use authorization, these cases underscore the need to remain vigilant in the early days of the vaccine campaign.”
While Pfizer’s vaccine contains slightly different ingredients than Moderna’s, both vaccines rely on mRNA — not live viruses — to produce an immune response in the body. It’s unknown at this point what the potential allergen might be.
Moderna pointed out Thursday that its manufacturing process is cell free and contains no human or animal products, preservatives or adjuvants.
Moderna noted two anaphylactic reactions during their latest trial — one in a placebo recipient that occurred 10 days after the first dose of saline, and the second one 63 days after the second dose of actual vaccine in a woman with a history of asthma and a known allergy to shellfish, officials said Thursday.
What to do with trial participants who got placebos?
Another major question during the daylong meeting was how to continue ongoing clinical trials and work with those who received a placebo, now that two emergency use vaccines have been authorized, or requested to be authorized.
Robust scientific trials — including vaccine trials conducted by Moderna and Pfizer — are done in a double-blind fashion, meaning that neither researchers nor participants know what shot they receive.
However, blinding is already “being eroded” because study participants who get a sore arm, fever, headache and muscle fatigue after their shots and read news coverage of the vaccine trials are very likely to guess that they got the vaccine, said Dr. Mark Sawyer, director of division of infectious diseases and a professor of clinical pediatrics at UC San Diego School of Medicine and a voting committee member.
There’s also nothing preventing participants from getting a test to see if they’ve developed COVID-19 antibodies.
The worry is that once people, especially health care workers, realize they’re up next to receive the actual vaccine, not a placebo, they’ll leave the study in order to get vaccinated. If they walk, researchers lose the potential to study them and draw long-term comparisons between vaccinated and unvaccinated groups.
The committee favored asking Moderna to allow participants to be unblinded, but only when it was their turn to be vaccinated, based on earlier-determined tiers. This would ensure fairness and equity, while also allowing for the most data gathering possible.
Other questions
There are also lingering questions about a potential connection between Bell’s palsy and Pfizer’s and Moderna’s vaccines.
In the Pfizer trial, there were four cases of temporary facial paralysis or drooping among the 22,000 study participants in three months, with Moderna noting three cases among 15,000, which translates to about 8 cases per 10,000 per year for each company, said Offit.
However, according to his calculations, there are only about 1.2 cases per 10,000 per year as a background population rate. Though the vaccine cases seem higher than a “background risk,” Offit recognized there’s not enough data yet to draw a causal link, and the FDA said it is looking into it.
Moderna has presented the FDA with three months of patient follow-up data thus far, with a very small number who have up to six months of follow-up, said Dr. Rachel Zhang, an FDA medical officer. Participants will be monitored for an additional 2 years.
Participants have been receiving monthly safety calls, as well as weekly eDiary prompts to record any physical concerns.
The most common reactions to the Moderna vaccine were mild-to-moderate swelling and tenderness at the injection site as well as fatigue, headache and muscle aches and pain.
Similar to Pfizer’s vaccine, there have been no studies on pregnant women, although 13 women in Moderna’s phase 3 study have since become pregnant and will be studied throughout the duration of their pregnancies.