Americans could have a second vaccine by the end of this week. Moderna’s coronavirus vaccine candidate appears set for regulatory authorization after the US Food and Drug Administration (FDA) found that it is highly effective in preventing confirmed cases of the illness. According to a 54-page analysis published by the agency, the two-shot regimen was 94.1% effective at preventing symptomatic disease in a trial of about 30,000 participants, with 11 cases in the vaccine group and 185 in the placebo group, thus meeting the “predefined success criteria” for emergency use authorization (EUA).
The vaccine candidate was particularly effective against severe disease. There were 30 cases of severe coronavirus in the clinical trial, but none of them in the group that got the vaccine. “The known benefits among recipients of the proposed vaccine relative to placebo are reduction in the risk of confirmed Covid-19 occurring at least 14 days after the second dose of vaccine, reduction in the risk of confirmed severe Covid-19 occurring at least 14 days after the second dose of vaccine,” wrote researchers. They add, “The vaccine efficacy in participants 65 years and older appears to be lower than in younger adults 18 to less than 65 years (86.4% compared to 95.6%).”
On November 30, Moderna submitted its EUA request to FDA for its investigational coronavirus vaccine (mRNA-1273) intended to prevent the illness. The proposed dosing regimen is 2 doses, 100 μg each, administered 1 month apart. A meeting of the Vaccines and Related Biological Products Advisory Committee (VRBPAC) is being convened on December 17 to discuss the same. The latest findings set the Moderna vaccine up for EUA by the FDA, meaning Americans could have two vaccines by this weekend, after the first shots of Pfizer-BioNTech’s vaccine were given to healthcare workers on December 14.
Citing sources, a New York Times report indicates that the FDA plans to issue EUA on December 18. In the case of Pfizer, after the advisory panel’s nod on December 10, it was granted a green light by regulators a day later.
One point of contention about the Pfizer-BioNTech vaccine — whether it should be authorized for use in 16- and 17-year-olds — will likely be avoided with Moderna, because the company is seeking clearance to use the vaccine in people 18 and older.
There were no serious safety concerns. The agency emphasizes that the number of participants in the Phase 3 safety population meets the expectations described in FDA’s guidance on the development and licensure of vaccines to prevent coronavirus. “The safety profile of mRNA-1273 was generally similar across age groups, genders, ethnic and racial groups, participants with or without medical comorbidities, and participants with or without evidence of prior SARS-CoV-2 infection at enrollment,” it adds.
According to scientists, there appears to be some protection against coronavirus following one dose, but these data do not provide sufficient information about longer-term protection beyond 28 days after a single dose
Preliminary evidence also suggests that it may prevent some asymptomatic Covid-19 cases. Moderna data shows that 38 trial participants in the placebo arm tested positive for Covid-19 without exhibiting symptoms at the time of their second dose, nearly triple the number in the vaccine arm of the trial. “Amongst baseline negative participants, 14 in the vaccine group and 38 in the placebo group had evidence of Covid-19 infection at the second dose without evidence of Covid-19 symptoms. There were approximately 2/3 fewer swabs that were positive in the vaccine group as compared to the placebo group at the pre-dose 2 time points, suggesting that some asymptomatic infections start to be prevented after the first dose,” noted Moderna.
More data are needed to fully understand the finding, but preventing asymptomatic illness is critical in the fight against Covid-19 as it can help reduce disease transmission. The FDA recommends additional evaluations to assess the effect of the vaccine in preventing asymptomatic infection.
What about adverse reactions?
The most common solicited adverse reactions associated with mRNA-1273 were injection site pain (91.6%), fatigue (68.5%), headache (63.0%), muscle pain (59.6%), joint pain (44.8%), and chills (43.4%). Severe adverse reactions occurred in 0.2% to 9.7% of participants, were more frequent after dose 2 than after dose 1, and were generally less frequent in participants 65 years and older as compared to younger participants.
“Among unsolicited adverse events of clinical interest, which could be possibly related to the vaccine, using the November 25, 2020 data cutoff, lymphadenopathy (axillary swelling and tenderness of the vaccination arm) was reported as an unsolicited event in 173 participants (1.1%) in the vaccine group and 95 participants (0.63%) in the placebo group. Lymphadenopathy was a solicited adverse reaction observed after any dose in 21.4% of vaccine recipients less than 65 years and 12.4% of vaccine recipients 65 years and older, as compared with 7.5% and 5.8% of placebo recipients in those age groups, respectively,” the findings state.
There were no anaphylactic or severe hypersensitivity reactions with close temporal relation to the vaccine. As of December 3, 13 deaths were reported, 6 in the vaccine group and 7 in the placebo group.
Throughout the safety follow-up period to date, there were three reports of Bell’s palsy (also reported by participants in the Pfizer trial), a type of facial paralysis (Bell’s palsy) in the vaccine group, and one in the placebo group. Experts, however, explain that currently, available information is insufficient to determine a causal relationship with the vaccine.
“One case of Bell’s palsy in the vaccine group was considered a severe adverse event; a 67-year-old female with diabetes was hospitalized for stroke due to new facial paralysis 32 days after vaccination. This case was reported as resolving. Another Bell’s palsy case in the vaccine group occurred 28 days after vaccination in a 30-year-old female who reported an upper respiratory infection 27 days before the onset of her facial paralysis. This case was reported as resolved. An additional case of Bell’s palsy in the vaccine group occurred 22 days after vaccination in a 72-year-old female; this event was still ongoing at the time of safety report,” reveals the report.
More studies planned
Studies will include completion of long-term follow-up from ongoing clinical trials as well as three planned surveillance studies. Moderna plans to establish a passive pregnancy registry to monitor vaccination during pregnancy within populations expected to receive the vaccine under EUA and to submit a protocol for FDA review and approval. Another is an active safety surveillance activity conducting retrospective analyses of medical and pharmacy claims data and the planned duration is through December 2022.
A real-world effectiveness analysis will be conducted at Kaiser Permanente Southern California (KPSC) to evaluate vaccine effectiveness in preventing laboratory-confirmed and clinical Covid-19 infection, hospitalization, and death. “Vaccinated participants will receive Moderna Covid-19 vaccine between January 1, 2021, and December 31, 2021, and the comparator group will be age-matched, unvaccinated KPSC members. The planned study duration is through December 31, 2023,” it notes.
What remains unknown?
Duration of protection: As the interim and final analyses have a limited length of follow-up, it is not possible to assess sustained efficacy over a period longer than 2 months, explains the authors.
Vaccine effectiveness against transmission: According to the FDA, data are limited to assess the effect of the vaccine against Covid-19 transmission from individuals who are infected despite vaccination. Additional evaluations will be needed to assess the effect of the vaccine in preventing virus shedding and transmission, they suggest.
Effectiveness in certain populations: Scientists stress that the subsets of certain groups such as immunocompromised individuals (such as those with HIV/AIDS) are too small to evaluate efficacy outcomes.
Effectiveness in pediatric populations: No efficacy data are available from participants ages 17 years and younger.
Vaccine effectiveness against death: According to scientists, a larger number of individuals at high risk of Covid-19 and higher attack rates would be needed to confirm the efficacy of the vaccine against mortality. Benefits in preventing death should be evaluated in large observational studies following authorization, they propose.