FDA Advisory Committee Votes to Support EUA for Moderna's COVID-19 Vaccine

5:15 PM Update: The Vaccines and Related Biological Products Advisory Committee (VRBPAC) has voted 20-0 with 1 abstention to support the benefit-risk profile associated with Moderna’s COVID-19 vaccine mRNA-1273.

Discussion over the VRBPAC committee vote question focused on whether or not the totality of evidence available on the benefits of mRNA-1273 outweigh the risks for use in individuals aged 18 years or older. The panel was in strong agreement that the answer to this question was yes. Many of the expert members expressed that the preponderance of data proves that the vaccine is safe and effective.

The meeting adjourned shortly after the vote was announced, with 3 members of the panel explaining why they voted the way they did.

The 1 abstention stated that he was uncomfortable with the wording of the voting question. He expressed his concern that in the midst of a pandemic, a blanket statement like “18 years or older” is too broad, and that it could be interpreted as full approval in the minds of the general public. He said that he wasn’t sure if the benefits of the vaccine do in fact outweigh the risks.

The committee's supporting vote precludes a decision from the FDA on the Emergency Use Authorization (EUA) application from Moderna, just a week after the panel granted one to Pfizer. This would make Moderna's candidate the second COVID-19 vaccine approved for an EUA in the United States.

3:20 PM Update: During the FDA’s discussion about the phase 3 trial data of Moderna’s mRNA-1273, the interim analysis was mostly used, as the final efficacy analysis was submitted after the initial EUA request. However, the FDA did state that they have since independently reviewed a majority of the final analysis data and confirmed that they found no notable differences.

The FDA found that the totality of clinical data that was submitted with the EUA request met the expectations for duration of follow-up and that efficacy outcomes were consistent across demographic subgroups. They found no serious safety concerns, most notably no anaphylactic reactions, associated with the vaccine.

Their benefit-risk assessment observed that there was a reduced risk of confirmed COVID-19, as well as severe infection, at least 14 days after completing a two-dose vaccination regiment in individuals without a prior history of SARS-CoV-2. There were noted limitations of the risk assessment though, including the time of follow up duration and the exclusion of pregnant women from the study.

The FDA additionally requested information about the most critical data to further inform vaccine safety and effectiveness to support licensure, including ongoing clinical trials with the vaccine and any other trials or observational studies.

Also pointed out was the issue of important missing information in regard to the pharmacovigilance plan that was submitted by Moderna with the EUA application, including:

• Use in pregnant and breast-feeding women
• Use in pediatric populations 
• Long-term safety and effectiveness
• Immunogenicity in subjects with immunosuppression
• Concomitant administration with non-COVID vaccines

1:25 PM Update: The public input portion of the VRBPAC meeting for Moderna’s COVID-19 vaccine saw a mainly positive outlook on mRNA-1273 from clinical experts and patient group advocates. However, there were plenty of criticisms about the company and COVID-19 vaccines in general.

Diana Zuckerman, PhD, president of the non-profit National Center for Health Research, voiced concerns that the two-month follow up was too short and that there was not enough diversity in the trial to support vaccination in underrepresented populations. She stressed that the definition for severe cases was too loosely defined, and that data is still needed on long term care patients.

Stating the vaccine was clearly effective, she expressed that the lack of long-term data is worrisome, and that the FDA should authorize an EUA, but it should be given only to priority populations until more data is collected.

Renumathy Dhanasekaran, MD and professor at the School of Medicine at Stanford University, viewed the vaccine as a welcomed relief for older patients and those with chronic diseases, as these are the populations who need it most. She said that she was happy with the studies demographics and vulnerable communities’ representation and that mRNA-1273 will help them considerably. She views the benefits of the vaccine as far outweighing the risks, especially in patients with comorbidities.

Douglas Dieterich, MD, a physician at Mount Sinai Hospital in New York, came to the meeting not as an expert, but as a patient. In mid-March, he was infected with COVID-19 and has subsequently experienced numerous, severe long-term symptoms. He said that it is important to recognize that prevention is vital, as the long-term impacts of the virus are prevalent. He believes that the vaccine is the answer to this problem, and that he will be receiving one when his time comes.

While more data is needed for pregnant women and children, Jasmine Marcelin, MD, was encouraged by the efficacy rate and lack of adverse events in Moderna’s product. She encouraged the FDA to grant an EUA to the company for its vaccine. She also said that it is important that there is appropriate messaging and advertising to accompany the rollout so that the public may be educated on the therapy and be able to make informed decisions.

11:50 AM Update: In their presentation, Tal Zaks, the Chief Medical Officer of Moderna, stressed that mRNA-1273 is based on well understood biology and that it is not the company’s first developed vaccine. Moderna has undertaken 12 clinical trials since 2015 and has invested heavily in clinical quality attributes to improve their processing and manufacturing capabilities.

He stated that Moderna believes the results from their phase 3 trial supports an EUA recommendation and eventual licensure. He acknowledged the need for further data and monitoring of the vaccine and said that they are committed to longer term data observance and collaboration with U.S. administrations.

Jacqueline Miller, senior vice president, elaborated on the data gathered from the trials assessing the vaccine. The ongoing study has included 30,351 participants and has an established 94.1% efficacy rate in the final scheduled analysis on the primary endpoint. The participants were stratified by age and health risk into 3 groups to ensure an appropriate assessment of potential underlying comorbidities. The data has demonstrated clear and compelling evidence of COVID-19 prevention.

Dr. David Martin, vice president of pharmacovigilance, discussed the company’s post authorization EUA safety monitoring systems. Moderna will address any concerns associated with the vaccine, identifying and assessing as rapidly as possible any known adverse reactions with mRNA-1273.

They will follow all vaccine administrations, providing new updates every 2 weeks, including links to open claims data that can be connected to subsequent adverse events. This will allow for the addition of new safety signals to monitor them.

10:15 AM Update: Dr. Peter Marks, the director of the Center for Biologics Evaluation and Research (CBER) at the FDA, stated that this week’s meeting would be organized differently in comparison to last weeks, to allow speakers time for a more robust discussion. The prior meeting has been made available in order to skip long talks on data and allow them to be geared more directly to the EUA for mRNA-1273.

Doran Fink, the Deputy Director of the Division of Vaccines and Related Products Applications, described how the ongoing COVID-19 pandemic has been worsening, with 16 million cases and more than 300,000 deaths to date, with an additional 1.5 million cases occurring in the past week.

The FDA has been conducting an in-depth review of Moderna’s phase 3 trial data to establish the verified clinical data’s integrity. Independent analysis, along with a review of manufacturing and non-clinical data information, has been gathered to inform both the public and vaccine recipients.

The panel of experts gathered is expecting clear and compelling data, as well as plans for further vaccine distribution and effectiveness, to support the issuance of an EUA to Moderna. In order for an EUA to be granted, the benefit-risk profile must be determined as favorable based on the current data.

It was noted that there have been anaphylactic reactions following vaccine administration in the UK and Alaska in healthcare workers who received the Pfizer vaccine, and that the FDA is coordinating with the CDC to monitor them, which they will continue to do with Moderna if an EUA is issued to the company.

This is relevant for today’s meeting due to the similar nature of Moderna’s mRNA-1273 with Pfizer’s BNT162b2. These instances underscore the importance to stay vigilant on possible adverse reactions.

8:00 AM Update: Today, the US Food and Drug Administration (FDA) Vaccines and Related Biologic Products Advisory Committee (VRBPAC) will gather to discuss whether or not they will grant an Emergency Use Authorization (EUA) application to Moderna’s mRNA-1273 vaccine for the prevention of coronavirus disease 2019 (COVID-19) in persons aged 18 years and older.

The full-day meeting will focus on the evaluation of the phase 3 trial data by an independent panel of experts, along with input from the public, during an agenda of sessions and open discussion. A vote will then be taken at the end on the therapy’s benefit-risk ratio for its prospective use as a preventive vaccine for confirmed COVID-19.

Taking into account the similarity of Moderna’s mRNA vaccine with Pfizer’s BNT162b2, which was approved for an EUA last week following the VRBPAC meeting, it is anticipated that mRNA-1273 will meet the same fate.

This page will be updated throughout the day of Thursday, December 17, with details and perspectives shared during the VRBPAC meeting. Be sure to check back in, and follow Contagion® on Twitter.