Modern problems call for Moderna solutions

Ava Levinson and Quinn Liu

On the morning of November 16, just eleven months after beginning work on their COVID-19 vaccine, Moderna Therapeutics released results showing an efficacy rate of 94.5%. Of the over 30,000 participants in their Phase 3 trial, 95 confirmed cases of COVID-19 were evaluated—90 who had been given a placebo and 5 who had been given the vaccine. Eleven of the confirmed cases were diagnosed as severe, but none of them had been given the vaccine. The data demonstrates that with the Moderna vaccine, one would have a 95% chance of immunity against COVID and a 5% chance of contracting mild disease, avoiding hospitalization and fatalities. While both Moderna’s and Pfizer’s vaccine will require two doses around four weeks apart, the latter has to be stored in specialized freezers at about -94 degrees Fahrenheit, while Moderna’s is stable in regular refrigerators at 36 to 46 degrees Fahrenheit. Upper School parent and Moderna CEO Stephane Bancel P’21,’22 spoke with The Vanguard about how he reacted to hearing the results, what the past months have been like for him and his team, and whether he is optimistic about an end to the pandemic.

—Ava Levinson and Quinn Liu (both ’21)

The meeting with the NIH Data and Safety Monitoring Board (DSMB) took place on Sunday, November 15. How were you feeling in the days leading up to the announcement and during the meeting?
I was nervous. We’d worked so hard since January to get this vaccine working, and we were anxious that it wouldn’t work. I was here at home, and I was trying to keep busy by looking at emails and files for Monday meetings, but I just couldn’t focus because I was so anxious. Then around 1 p.m., the president of our company texted me, “Get on this WebEx, there’s a link right in your inbox, click on it.” So I click on the invite, get on WebEx, and there are around 10 people from the company. And then the head of the DSMB joins our meeting, and he gives us the conclusions. He starts to say, “OK, so there were 95 participants in the study who got the disease.” And then he paused, which felt like a year, and we were like, “Just tell us!” And he’s like, “90 people were on placebo.” So I knew, OK, 94.5% efficacy—it’s working. And then he said, “There were actually 11 severe cases of COVID disease. Of those 11 cases…” And then again, he pauses, and we’re like, “Jeez! Just tell us.” And because it’s 11 [cases], it’s so absurd to think that they will all be in the placebo group, so you start worrying that they’re all on the vaccine. And he said, “Eleven were on placebo, and zero were on the vaccine. I think this vaccine is going to be amazing.” I mean, it’s funny, you guys have seen Dr. Tony Fauci, who runs the infectious disease division of NIH, who is amazing. Tony was on the call, and he went crazy. He’s 79, and he’s like, “This is going to change the world.” He was so happy! It was funny.

How did you feel after receiving the news?
It was a very nice feeling. When it was done, I left my office, and I called in my wife, Brenda. And Chloé [Bancel ’21] came down from her room, and we called Olivia [Bancel ’22] in. And I said, “Look, it’s 95.4% efficacy.” And we just hugged each other, crying.

What’s amazing about my job is that you use science and the talent of a world-class team to all come together—because it takes a village to make a medicine—and all work to try to make other people’s lives better. And you know, it’s a hard business; 90% of drugs that go from the labs in animal testing to human testing never make it to the end. And think about this one—we started in January on this new virus that nobody knew of, and in two days we designed the vaccine on the computer. When we started Moderna in 2011, my wife said to me, “So, I understand if mRNA works as a new class of medicine, it’s going to impact millions of lives. But what is the chance it’s going to work?” And I told her, “Maybe 5%. But if it works, it’s going to impact so many millions of lives. I would rather take a 5% chance of doing something that can help millions of people than a 95% chance of doing something that will help five people.”

Do you think future vaccines will be able to be made this quickly?
I think they’ll be able to be made much, much quicker, but I don’t think as quickly. We took a lot of business risks to go faster—it was very clear to the government and us that we weren’t going to take safety risks. If you think about it, the difference between a vaccine and a cancer drug is you give a vaccine to a healthy person. When we do clinical trials, we’re very worried as a company because we’re giving that drug to people who are very healthy. If something went wrong, we’d just feel terrible. So I think even with new vaccines, we’re going to go much faster because of the amount of technology that has now been programmed to go much faster, but we probably won’t be able to go as fast because we used government money to take a lot of business risk.

A 95.4% efficacy rate is great news. What happens now?
With 95% efficacy, and the fact that those who get COVID with the vaccine will only get a mild case versus severe case, I think there’s a high probability, around 95+%, that this vaccine is going to get approved. So what is ahead of us now?The data we released on Monday [Nov. 16] is called a first interim look. So basically, we froze the data to a certain point of time to look at it to say, “How does it smell? Is it good, or bad, or do we not know?” Those were basically the three outcomes we could’ve had on Sunday [Nov. 15]. We got, of course, a good outcome. The next step is to continue with the trial so that as more people get COVID, we reach a certain number to get the strongest statistically significant Phase 3 trial. This was reviewed and approved by the FDA back in June. In our case, given the 30,000 subjects, the math worked out so that we need 151 cases of COVID to be able to determine whether or not the vaccine is working in a statistically significant way. When they reviewed the data on Sunday, we had 95 cases. Because there are so many cases in the Midwest right now, we anticipate either this week or next week that we will reach the 151-case threshold. So what do we do when that happens? We clean up the data, do quality control, check everything; we send it again to the independent safety board; they will review it; and it will be filed to the FDA. And, basically, with that data package, we will say, “Mister FDA and Madam FDA, this is the data of the vaccine, and we would like to ask you for an approval.” The FDA has the highest bar of quality in the world for approving medicine, which is amazing and great. So they will review a file and ask an independent advisory board of experts—infectious disease doctors, statisticians, and physicists—to basically look at the FDA data. The data will be public, so anybody in the U.S. will be able to Google the link and look at the Zoom, where you’re going to have all the data posted online, three or four days before we meet, so any scientist can look at the data and make their own opinions. So, basically, the process is: companies send raw data to the FDA, who analyze it and put their analysis online a few days before a meeting between the independent advisory board, the FDA, and the company scientists. This should happen around the first half of or mid December, based on the current timeline that’s ahead of us. If they are comfortable that the data we’re presenting is strong enough to warrant an approval, we should get one in a couple days.

How has the president’s Operation Warp Speed influenced your process?
We’re working now with Operation Warp Speed, which was set up by the government to accelerate and help the industry and government agencies. If you think about it, there’s the FDA, NIH, the CDC, and BARDA (Biomedical Advanced Research and Development Authority) managing the money. So within Health and Human Services (HHS), you have a lot of divisions that usually don’t speak super closely with each other. But in the case of a crisis, where every hour matters, they created Operation Warp Speed as an umbrella to coordinate and make sure everybody talked daily and was an interface with industry. So for somebody like us—or Pfizer or anybody in industry that has a vaccine in the clinic—you could say to the government, “I need an answer to a question now.” Usually this would take months because the NIH would have an opinion, FDA would have an opinion… So if you’re in industry and trying to get guidance, sometimes you waste a month or so. Since we’re in a pandemic and losing 1000 Americans a day, wasting a month or two would be a tragedy because of bureaucracy. That makes Operation Warp Speed very unique in terms of time—I’ve never seen this in the 25 years I’ve been doing this.

Are you optimistic about an end to the pandemic?
What I think will happen based on where we are today is in the first quarter of next year, the vaccine will be approved, mostly for people at very high risk. We initially said that we would make and ship 20 million doses by Christmas. And it would not be appropriate for me as a CEO to decide who gets it. In the second quarter, around May and June, because we’ve added a lot of manufacturing capacity, we hope to provide the vaccine to every American 18 and older. So as soon as it’s approved and the quality control team clears it, it will be shipped into the U.S. and will be available for purchase. For 12- to 17-year-olds, I think it will be around the summer when we get that data. You do not start dosing those teenagers until you get data showing the vaccine’s safety and efficacy for that age group. Since you give a vaccine to healthy people, the last thing you want is to take the risk of hurting a teenager because they have their entire life ahead of them. Once the vaccine looks very good efficacy-wise, with mild side effects, we will start all studies with 12- to 17-year-olds before the end of the year, which we anticipate will be relatively fast. So I hope that by the May/June time frame, we will have the data for that. And then for the younger children from a few months old to 11 years old, we will start the study early in the new year. That is going to take much longer and will be finished I think around Christmas next year, because with testing a vaccine in younger children, you go down in age very slowly. For example, you start trials with 11-year-olds, and then 10, and then 9, usually waiting three to four weeks in between to make sure there are no safety issues. We have to do it this way because young children have very few cases of COVID. If this was like the Spanish Flu in 1918, where as many old people were dying as young people, then the FDA and industry would be more aggressive getting data from children. But, thankfully, that’s not the case.

You’ve had a busy year. What do you do to relax?
What I’ve learned is that the more intense the peril I am in, the more I need to do sports. Every morning at 4:00 a.m., I get up, put on my tennis shoes, and do 10 to 15 minutes of weightlifting because I’m getting old. Keeping muscle mass is important—you lose 1% to 2% a year. You guys don’t even know that because you don’t have that problem. Then I go for a run. What I love is I can just run down the street, take the pass rail, and go to the Esplanade and run for an hour, a 10K or so. I take no music—it’s very calm. It’s nice because I can think, and doing sports gives me a lot of oxygen. It’s helped me a lot to stay sane with the pressure, the public attention, and weight on our shoulders. The toll of this pandemic has been awful, and the mental health problems around the country are increasing. If you think about it, we as a species aren’t supposed to be locked down; thousands of years ago we were in the forest eating fruits from trees. This is not good for our psyche. And that worries me deeply for the mental health problems of all age groups, which is why I force myself every day, even when I’m tired, to get up early and go do sports. And I think it’s helped me tremendously. I think I, along with the team, only had two real weekends. Two weekends where I had no board meetings, no conference calls. But you can see that we can’t waste time now; thousands of Americans are dying every day. So I hope, knock on wood, we are close to having a vaccine that can be used to help millions of people around the world.