The Food and Drug Administration on Tuesday confirmed that the coronavirus vaccine developed by Cambridge biotech Moderna appears to be highly effective and safe, setting the stage for the agency to clear the second genetic vaccine to prevent COVID-19 for emergency use within days.
Only four days after the drug regulator approved a similar vaccine developed by New York-based Pfizer and its German partner BioNTech, the FDA found that Moderna’s vaccine prevented more than 94 percent of COVID-19 cases in a late-stage clinical trial and raised no major safety concerns.
A panel of outside experts is expected to vote Thursday on whether the FDA should authorize the vaccine for emergency use, as coronavirus deaths in the United States surpass 302,000. Assuming the committee makes that recommendation, the agency would likely act swiftly, and the second vaccine could start being rolled out soon afterward.
In advance of Thursday’s advisory panel hearing, here are some questions and answers about Moderna’s vaccine:
How does it compare with the one developed by Pfizer and BioNTech?
Broadly speaking, they’re very similar. Both rely on synthetic messenger RNA, an ingenious variation on the natural substance that directs cells to produce proteins. While traditional vaccines inject a dead or weakened virus into the body to stimulate an immune response, mRNA vaccines use custom-made messenger molecules that tell cells to create a viral protein. In the case of both COVID-19 vaccines, they instruct cells to create the distinctive spike protein on the coronavirus. Once that happens, the body’s immune system generates antibodies to fend off the disease if the recipient is exposed to the virus. No mRNA vaccine had ever been deployed until drug regulators in several countries, including the US, recently cleared the Pfizer-BioNTech vaccine for emergency use.
Are there other similarities?
Yes, several. Both vaccines require two shots (three weeks apart for the Pfizer-BioNTech vaccine, four weeks apart for Moderna’s). The Pfizer-BioNtech vaccine prevented 95 percent of COVID-19 cases in a late-stage study of more than 43,000 volunteers, half of whom got the vaccine and half of whom received a placebo. The Moderna vaccine prevented 94.1 percent of cases in a similar study of some 30,000 volunteers, who also had a 50-50 chance of getting the experimental substance. Both vaccines appeared to work well regardless of age, gender, race, and ethnicity of participants. Both were also highly effective in fending off severe cases of COVID-19. And neither appeared to cause any alarming side effects.
What are the differences between the two vaccines?
Some information on how the vaccines were made is proprietary. Robert Langer, the prolific inventor and biomedical engineering professor at the Massachusetts Institute of Technology who cofounded Moderna, said, “I don’t think anybody has done a head-to-head comparison of the Pfizer one and the Moderna one.” In other words, the vaccines are like two chocolate fudge cakes with closely guarded recipes. Still, Langer said, there may be subtle but important differences between the vaccines in two key areas: the super-tiny fatty bubble that delivers the mRNA into cells, and the messenger molecule itself.
The lipid nanoparticle that ferries the molecule into cells is composed of four ingredients, he said, and in the two vaccines those ingredients probably differ. The same is likely true with the mRNA, which instructs cells to make the coronavirus protein. Slight variations in biomedicine can have a huge impact. “We know that if you change one amino acid in hemoglobin, you go from being a healthy person to having sickle cell anemia,” Langer said.
The variations may contribute to an obvious difference between the vaccines: temperature requirements for storage. The Pfizer-BioNTech vaccine must be kept at minus 94 degrees Fahrenheit in freezers and in custom-made “cool boxes” packed with dry ice so it doesn’t spoil during distribution. Moderna’s vaccine can be stored at a comparatively balmy minus 4 degrees Fahrenheit without going bad.
The youngest age that people could receive the vaccines under the emergency use authorization is also different. Moderna has asked the FDA to clear its vaccine for people age 18 and over. Pfizer’s vaccine was cleared for use in people age 16 and older, although that caused some debate in last week’s advisory committee meeting.
What about side effects?
Both vaccines were linked to mild to moderate side effects, including pain at the injection site, fatigue, headache, and fever. Some appeared to be more significant with the Moderna vaccine. The side effects for both vaccines were generally more common and noticeable after the second dose. As a result, some experts say people may need to take a day off from work after the second shot. But none of the side effects alarmed regulators.
Dr. Eric Rubin, editor-in-chief of the New England Journal of Medicine and a member of the advisory committee that will meet Thursday, said inflammatory reactions probably stem from the lipid nanoparticle that each vaccine uses to deliver the messenger molecule into cells. Those reactions might actually be a good thing, he said, prodding the body to mount an immune response. “You want that to happen,” said Rubin, who is also a professor at the Harvard T.H. Chan School of Public Health.
Are there any other side effects that people should consider?
In the Moderna trial of roughly 30,000 volunteers, there were three cases of Bell’s palsy ― or temporary facial paralysis ― in the vaccine group, and one in the placebo group. (That’s three cases among 15,000 people, since half of the volunteers got the vaccine.) In the Pfizer trial, there were four reported cases of Bell’s palsy, and all four were among the roughly 21,500 recipients who got the vaccine rather than a placebo. Those rates are higher than the expected one of 1.2 cases of Bell’s palsy for 10,000 people a year, according to Dr. Paul Offit, an infectious disease expert at Children’s Hospital of Philadelphia who sits on the advisory committee. “This is not a deal-breaker obviously, but it needs to be followed up,” he said. “You need to make sure this isn’t a coincidental association but a causal association.” The FDA said Tuesday it will recommend that vaccinated people be monitored for the condition.
How long does the Moderna vaccine confer immunity compared with the Pfizer-BioNTech vaccine?
No one knows yet. Both vaccines were developed in less than a year, which shatters the record set by a mumps vaccine that took four years to go from collection of viral samples to licensing in 1967. Such breathtaking speed means regulators haven’t collected data nearly long enough to gauge the duration of immunity.
If the FDA approves the Moderna vaccine, how many doses will be available in the United States, and how does that compare with the Pfizer-BioNTech vaccine?
At least 40 million doses ― enough for 20 million people ― should be available from the makers of both vaccines combined by the end of the year, according to federal officials, and many more are expected next year. The federal government has so far ordered 100 million doses of the Pfizer vaccine and 200 million doses of the Moderna vaccine. It could buy more doses from the companies, and will probably buy other vaccines in late-stage trials, if they prove effective and safe. A third vaccine, from Johnson & Johnson, which uses a different scientific approach and was developed with help from Beth Israel Deaconess Medical Center, is in a late-stage clinical trial. Results are expected early next year. That vaccine would require only one shot, which could be a significant advantage.
Jonathan Saltzman can be reached at email@example.com.