乌鸦传媒

Moderna's COVID-19 vaccine candidate, mRNA-1273, seemed to meet criteria for emergency use authorization (EUA), agency staff said in a released on Tuesday.

And as with the Pfizer/BioNTech product that won authorization last week, the technical review found few issues with Moderna's trial data.

The vaccine is set to go before the FDA's Vaccines and Related Biological Products Advisory Committee on Thursday, in the second such meeting of the group in a week. On Dec. 10, the panel voted 17-4 to recommend the Pfizer/BioNTech vaccine, and the FDA granted the EUA late the next day.

Similar to last week, the committee will decide whether, based on the totality of scientific evidence, the vaccine "may be effective" in preventing symptomatic COVID-19, and whether the benefits outweigh the risks.

And similar to last week, FDA technical staff did not raise any serious concerns. Notably, Moderna is requesting authorization for the vaccine to be used in adults 18 and older -- unlike the Pfizer/BioNTech vaccine, which was authorized for adolescents as young as 16 despite limited data. That proved to be a sticking point for the "no" voters at last week's meeting.

on Nov. 30, when the company submitted its EUA application, indicated vaccine efficacy of 94.1%, with clinical illness plus a positive coronavirus PCR test as the primary efficacy outcome. Among more than 30,000 people randomized 1:1 to the active vaccine or placebo, 11 COVID-19 cases were seen in vaccine recipients versus 185 in the placebo group.

Moreover, the vaccine was 100% effective against severe COVID-19, with 30 cases in the placebo group and zero in those vaccinated, the company said.

Final results have not yet appeared in a peer-reviewed journal. But some of the topline findings were confirmed and expanded in the briefing documents made public Tuesday. It also indicated overall vaccine efficacy of 94.1% (95% CI 89.3%-96.8%) as well as efficacy for age subgroups. Older participants were not as well protected, this analysis showed:

• Adults younger than 65 (95.6%, 95% CI 90.6%-97.9%)
• Ages 65 and older (86.4%, 95% CI 61.4%-95.5%)

Data supporting the application were primarily from study -- dubbed COVE by Moderna -- a phase III, randomized, placebo-controlled trial co-sponsored by the National Institute of Allergy and Infectious Diseases. It included about 30,500 adults ages 18 and older; the two required doses were given 28 days apart.

For purposes of the efficacy analysis, clinical illness was defined as at least two systemic COVID-19 symptoms and at least one respiratory symptom.

Mean age at vaccination was about 52, and about 53% were men. Only a quarter of participants were older than 65, about 10% were Black and 20% were Hispanic or Latino. Some 20% of participants had a high-risk condition, a quarter were healthcare workers, and 80% had "occupational risk," such as from work in healthcare, emergency response, or retail/restaurant operations.

Examining safety, nearly all participants experienced injection site pain, with about two-thirds reporting fatigue and headache, and almost 60% reporting muscle pain. Mild to moderate reactogenicity was more common in adults younger than age 65.

As of Dec. 3, 13 deaths were reported -- six in the vaccine group and seven with placebo. Two deaths in the vaccine group were older than age 75 with pre-existing cardiac disease; one died of cardiopulmonary arrest and one from myocardial infarction. Two patients were found dead at home, one with cardiac disease and one with hypertension and chronic back pain, whose cause of death was listed as head trauma. One patient had Crohn's disease and short bowel syndrome and had complications resulting in multi-organ failure after being hospitalized for obstructive nephrolithiasis and one patient died by suicide.

The most common severe adverse events occurring at a higher rate in the vaccine group versus placebo were myocardial infarction, cholecystitis, and nephrolithiasis, though FDA staff said the small number of these events do not suggest a causal relationship.

Lymphadenopathy was reported more frequently in the vaccine group versus placebo (21.4% vs 7.5% of adults younger than 65, and 12.4% vs 5.8% of adults ages 65 and older).

There was also a "numerical imbalance" in hypersensitivity (1.5% in vaccine group vs 1.1% in placebo), though there were no anaphylactic events or severe hypersensitivity reactions "with close temporal relation to the vaccine."

Three cases of facial paralysis or Bell's palsy were reported in the vaccine group and one in the placebo group, with FDA staff finding "insufficient" information to determine a causal relationship to the vaccine. No other vaccine-related neurologic, neuro-inflammatory or thrombotic events were reported and serious adverse events were rare in both groups (1.0% apiece).

There were insufficient data in children under age 18, pregnant and lactating individuals, and immunocompromised individuals.

The advisory committee meeting on Thursday will not only be webcast by the FDA, but also streamed on YouTube, Twitter, and Facebook.

Comment