Moderna Phase 3 Interim Report

Overview

On Monday, November 16th, Moderna, Inc. reported interim results from their large-scale Phase 3 clinical trial of mRNA-1273, a COVID-19 vaccine. The study shows that mRNA-1273 has an almost 95% efficacy in protecting against a SARS-CoV-2 infection. These results come only a week after Pfizer and BioNTech announced a 90% efficacy for their COVID-19 vaccine candidate, BNT162b2. Moderna’s Phase 3 trial has yet to conclude, but these impressive results continue to bring hope for an end to the COVID-19 pandemic. This article will offer background into mRNA-1273 and the Interim Report, bring insight into the vaccine’s distribution timeline and the outcomes of the results, and identify any unanswered questions.

Background on mRNA-1273

Moderna is one of only a few companies that have designed an mRNA-based vaccine, mRNA-1273. After isolating SARS-CoV-2 and sequencing its genetic code, the company translated the genetic code of the spike protein into mRNA (messenger genetic code that relays blueprints to protein synthesizing machines). As a vaccine, the mRNA is housed in a lipid nanoparticle, which is injected into immune cells and instructs them to begin making the spike protein as if it was infected by SARS-CoV-2. Other immune cells can recognize the proteins and create a defense against SARS-CoV-2 if the individual was ever infected.

Phase 1 testing began in February 2020 with candidates ranging from 18 to 71+ years of age. The trial is officially concluded with final results posted as of September 2020. The purpose of the trial was to determine which dose was best after one and two-doses. The researchers noted that the adverse reactions ranged from mild to moderate in severity, typically fatigue, headache, muscle aches, and pain at the injection site. The study concluded that the higher dose induced larger amounts of neutralizing-antibody titers.

Phase 2 testing began in late May 2020 where researchers are specifically testing two different doses in comparison to a placebo. Phase 3 trials began in late July where an expected 30,000 candidates will be randomly injected with either a 100mg vaccine or a placebo due to the results of Phase 1 testing. The researchers are specifically testing for prevention of severe COVID-19 symptoms and prevention of SARS-CoV-2 infection.

Interim Report for Phase 3 

Similar to Pfizer, Moderna released an interim report from their Phase 3 clinical trial that was conducted by an external, independent review team, Data Safety Monitoring Board (DSMB). DSMB had decided that Moderna’s study has met the statistical criteria for determining efficacy, which they deemed to be 94.5%. DSMB determined this from the 95 COVID-19 cases, 90 cases were from individuals in the placebo group while 5 cases were from those who received the mRNA-1273 vaccine.

DSMB also took secondary endpoints that analyzed the severe cases in the study. Moderna reported 11 severe cases of COVID-19, to which all 11 were from the placebo group. This result, although not well-supported, indicates that mRNA-1273 can reduce the severity of COVID-19, if not prevent it at all. 

Alongside these results, Moderna indicates that as the study continues and new data points accrue, the vaccine efficacy may change. As already mentioned in the Pfizer Report, the flu vaccine is found to only have 40% to 60% efficacy depending on the demographic. With even major changes in the study, the efficacy of mRNA-1273 could very easily match or rest above the flu vaccine’s efficacy. Furthermore, DSMB had no current concerns for severe adverse reactions, but expects Moderna to continue to collect this information as the study progresses.

Tentative Timeline 

mRNA-1273 is not available to the public and must undergo Food and Drug Administration (FDA) approval in order to do so. Moderna plans to submit a request for Emergency Use Authorization (EUA) in the next several weeks in order to begin production and distribution of mRNA-1273, but it must first collect a median of 2 months data in order to bring the proposal to the FDA. Pfizer also plans to submit the BNT162b2 vaccine for an EUA.

If approved, the company plans to have around 20 million doses produced by the end of 2020. Moreover, the company is on track to produce 500 million to 1 billion doses globally, by the end of 2021. 

As for public distribution, neither President Trump nor President-elect Biden have outlined logistical vaccine distribution campaigns. However, President-elect Biden has committed to investing $25 billion into manufacturing and distribution in order to guarantee a zero-cost vaccine for every American.

*Visit the CDC’s FAQ page on COVID-19 Vaccination.

Positive Outcomes 

First, as outlined in the Pfizer Report, it is become more and more obvious that there will likely be multiple successful COVID-19 vaccines. The two vaccines farthest in development and clinical trials have an mRNA mechanism. However, there are others that follow a more traditional approach, whether it be a weakened version of the virus or an inactivated vector. Moreover, multiple successful vaccines mean a shorter timeline for the COVID-19 pandemic as countries and communities are limited by the number of available vaccines. 

Second, a second successful mRNA vaccine brings further hope for the new class of vaccines. Currently, there are no mRNA vaccines on the market, but with proof of their high efficacy, traditional vaccines such as the flu, DTaP, HepA, etc., might be able to get redesigned and remanufactured with hope of more effective results.

Third, in comparison to Pfizer, Moderna appears to have the better vaccine, based on efficacy and logistics. Pfizer’s BNT162b2 is required to be stored at -94˚F (-70˚C), while Moderna’s mRNA-1273 has the capability of being stored at much more achievable temperatures. In a press release, Moderna revealed that their vaccine candidate remains stable for 6 months at -4˚F (-20˚C), 30 days at refrigerated conditions (36˚F, 2˚C), and 12 hours at room temperature. This allows for mRNA-1273 to be easily distributed to rural and developing communities.

Lastly, as stated in the Pfizer Report, high efficacy rates for COVID-19 vaccines can influence individuals into receiving a vaccine. With caution towards the safety and effectiveness of COVID-19 vaccines, high efficacy rates and moderate adverse side effects might be enough to vaccinate a great majority of the United States and the world, nearing towards herd immunity.

Challenges

Although Moderna defeats the problem of who has access to the vaccine, a new challenge is still present: how will the vaccine be distributed?

As stated earlier, there is no current mass distribution campaign proposed by President Trump, nor by President-elect Biden. There is only commitment towards investment. There’s fear that vaccine candidates are accelerating in their clinical trials, but the government is not prepared to supply, organize, and distribute vaccines when they become approved by the FDA by EUA. 

Furthermore, Moderna and Pfizer have vaccine candidates that require two doses. This causes two problems. First, although they might be able to produce millions, maybe a billion, doses, the number of individuals vaccinated is half of that. Second, there’s an expectation for patients to return about 28 days after the first vaccination, yet with mass distribution, there might not be a reliable system to log all patient information and assist in notification.

Unanswered Questions

Although these results reveal more about the COVID-19 pandemic, there are still questions left unanswered. 

First, Moderna won’t know how long immunity will last for their vaccine until a couple years after mass distribution. There might be some information on lasting immunity that comes from volunteers in earlier stages of the clinical trials. Moderna will be waiting with Pfizer and other vaccine companies for this information.

Second, there’s no clear understanding on whether mRNA-1273 can help prevent the spread of SARS-CoV-2 when the person is experiencing minimal to no symptoms. In other words, does the vaccine also function as a transmission blocker?

Third, who will get the vaccine first? When it comes to vaccine distribution, health professionals and vulnerable populations typically receive the vaccine first. That will most likely be the case in the COVID-19 pandemic, but as doses are being produced, it is unknown the demand for the COVID-19 and who will be first in line.  

Lastly, the specific efficacies in certain demographics are unknown. The interim report did not include information as to the ages of the volunteers who had COVID-19, bringing into question a skewed efficacy that doesn’t fit for the elderly demographic.

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*The Moderna logo and name are trademarked by Moderna, Inc.