FDA review clears path for second coronavirus vaccine, this one developed by Moderna

By the end of the week, the United States could have two coronavirus vaccines.

A vaccine developed by biotechnology company Moderna appears poised for regulatory clearance after a detailed data review by Food and Drug Administration scientists confirmed the two-shot regimen was “highly effective” in a clinical trial and carried no serious safety concerns.

The FDA is likely to authorize the Moderna vaccine as soon as Friday, according to a person with knowledge of the situation who spoke on the condition of anonymity because they were not authorized to discuss the issue. Anticipating that decision shortly, Gen. Gustave Perna, who is overseeing the federal effort to distribute vaccines, said Monday that the United States was preparing to ship almost 6 million doses of the Moderna vaccines to 3,285 locations in the first week.

“It will be a very similar cadence that was executed this week with Pfizer, where we’re hitting initial sites on Monday, follow on Tuesday and Wednesday,” Perna said.

The 54-page FDA document published Tuesday morning positions the Moderna vaccine to follow the same historic track as the Pfizer-BioNTech vaccine. After the agency gave a positive review of the Pfizer-BioNTech vaccine exactly a week ago, the shots were endorsed by a panel of outside experts Thursday and granted a green light by regulators a day later. The first doses were administered to health-care workers Monday.

Assessing Moderna’s vaccine, regulators said the two-shot regimen was 94 percent effective at preventing disease in the trial, and particularly effective against severe disease. There were 30 cases of severe COVID-19 in the trial, none of them in the group that got the vaccine.

They also confirmed the vaccine worked well in people of all ages, races and genders. Side effects were widespread, occurring in most recipients, but typically short-lived, including fatigue, headaches, muscle aches and pain at the injection site.

Additional data filed by the company suggested the vaccine might prevent asymptomatic infections, not just symptomatic cases of disease. A vaccine that protects against disease, but not infection would still be incredibly valuable. But epidemiologists have worried about a scenario in which people stop wearing masks but could remain vulnerable to asymptomatic infections and spread the disease to others.

The FDA review said there was not enough data to assess the vaccine’s protection against asymptomatic infection or whether it damped down transmission of the virus, and called for further studies.

One point of contention about the Pfizer-BioNTech vaccine—whether it should be authorized for use in 16- and 17-year-olds—will probably be avoided with Moderna, because the company is seeking clearance to use the vaccine only in people 18 and older. Last week, the company began testing its vaccine in adolescents.

Moderna’s vaccine will be reviewed Thursday by the same panel of independent experts who last week recommended the Pfizer-BioNTech vaccine. The data it will consider echoes the evidence that led to a 17 to 4 vote to authorize the Pfizer-BioNTech vaccine, which was 95 percent effective.

Paul Duprex, director of the Center for Vaccine Research at the University of Pittsburgh, said the vaccine looked effective and safe, with tolerable side effects and predicted it would be authorized soon. An advantage of the Moderna vaccine, he pointed out, will be its simpler logistics, because it does not require specialized ultracold storage conditions like the Pfizer-BioNTech vaccine.

“I like the fact that now we have something can be stored in a minus-20 [degrees Celsius] fridge—the same kind of fridge you keep your ice cream in,” Duprex said.

Moderna developed its vaccine in partnership with the National Institute of Allergy and Infectious Diseases, with the government underwriting the research and development of the vaccine and the advanced purchase of 200 million doses, bringing the government investment to $4.1 billion.

The FDA reviews of both the Pfizer-BioNTech and Moderna vaccines cement the success of a new genetic vaccine technology, which could be used to rapidly create vaccines for other diseases.

Older vaccines work by injecting dead or weakened virus to teach the immune system to recognize the real pathogen. In contrast, the messenger RNA technology at the core of the Moderna and Pfizer-BioNTech vaccines delivers a strip of genetic material called RNA, encased in a fat bubble, to a person’s cells.

Once inside a cell, the messenger RNA co-opts the machinery used to make proteins to build tiny replicas of the spike protein that studs the outside of the coronavirus. The immune system learns to recognize—and block—the spike.

In Moderna’s trial, 30,000 people were randomly assigned to receive either two shots of a vaccine given four weeks apart, or two saline shots. Neither the participants, nor the people running the trial knew who was in which group. Investigators then waited as people were exposed to coronavirus in their daily lives, to see whether there were more COVID-19 infections in the group that did not receive the real vaccine. They counted cases starting two weeks after the second dose, to measure how well the vaccine protected participants after the immune system had mustered a full response.

The numbers were decisive: There were 196 cases in the trial, all but 11 of them in the group that received the placebo shots. There were 30 cases of severe COVID-19, and one death from COVID-19 in the trial, also all in the group that received the placebo shots.

There was a suggestion that a first dose of vaccine afforded some protection from the virus, but not enough to draw conclusions. “These data do not provide sufficient information about longer term protection beyond 28 days after a single dose,” the review said.

One of the major outstanding questions about this and other coronavirus vaccines is whether they prevent infection, as well as disease. Since most cases of COVID-19 are asymptomatic, that question has major implications for whether people will need to continue wearing masks and social distance despite being vaccinated.

Larry Corey, a virologist at the Fred Hutchinson Cancer Research Center who co-leads the government’s clinical trial network responsible for testing coronavirus vaccines, is working on a proposal for a trial that would specifically test whether vaccines afford such protection. He would potentially be giving shots to college students and have them test themselves daily to see if they’ve become infected. He hopes that study could begin in January.

In an addendum Moderna filed to the FDA, the company presented a tantalizing hint: Upon receiving the second dose of vaccine, 52 people tested positive for the coronavirus without symptoms. Most of those people were in the placebo group, indicating the vaccine may have protected participants against asymptomatic infection.

There were three cases of Bell’s palsy, a temporary facial paralysis, in the group that received the Moderna vaccine, compared with one case in the placebo group. The people who developed Bell’s palsy had other risk factors, and the rate was similar to that expected in the general population. But the FDA concluded “a potential contribution of the vaccine to the manifestations of these events of facial palsy cannot be ruled out.”

Lymph node swelling was more common in the group that received the vaccine, with 16% of participants experiencing the symptom after the second dose. There were no severe allergic reactions, a concern that has emerged after two cases were reported in Britain after the first injections of the Pfizer-BioNTech vaccine.

Enrollment in Moderna’s trial was slowed down this summer because scientists were concerned it lacked sufficient racial diversity to determine whether it truly protected those at highest risk of the disease. In the end, a fifth of participants were Hispanic, 10% were Black and 4% were Asian. More than 40% of the participants were either over the age of 65 or had medical conditions that increased their risk of severe disease.

“The trial enrolled the right people at risk,” Corey said. “For us who were designing the trial and enrolling the people, that’s so fantastic.”