Moderna Inc.’s experimental vaccine is 94.5% effective in preventing COVID-19 based on interim data from a late-stage trial, the company said on Monday, becoming the second US drugmaker to report results that far exceed expectations.

Together with Pfizer Inc.’s vaccine, which is also more than 90% effective, and pending more safety data and regulatory review, the United States could have two vaccines authorized for emergency use in December with as many as 60 million doses of vaccine available this year.

The vaccines, both developed with new technology known as messenger RNA (mRNA), represent powerful tools to fight a pandemic that has infected 54 million people worldwide and killed 1.3 million.

Unlike Pfizer’s vaccine, Moderna’s shot can be stored at normal fridge temperatures, which should make it easier to distribute, a critical factor as COVID-19 cases are soaring, hitting new records in the United States and pushing some European countries back into lockdowns.

“We are going to have a vaccine that can stop COVID-19,” Moderna President Stephen Hoge said in a telephone interview.

Moderna’s interim analysis was based on 95 infections among trial participants who received the vaccine or a placebo. Only five infections occurred in volunteers who received the vaccine mRNA-1273, which is administered in two shots 28 days apart.

“The vaccine is really the light at the end of the tunnel,” Dr. Anthony Fauci, the top US infectious diseases expert said. He urged Americans not to let their guard down and to continue washing hands and being vigilant about social distancing.

Even with fast authorization, the vaccines will not come in time for most people celebrating the US Thanksgiving and end-of-year holidays, when families and friends come together—just the types of gatherings public health officials warn against.

Moderna expects to have enough safety data required for US authorization in the next week or so and expects to file for emergency use authorization (EUA) in the coming weeks.

SEVERE CASES

Moderna’s data provide further validation of the promising but previously unproven mRNA platform, which turns the human body into a vaccine factory by coaxing cells to make virus proteins that the immune system sees as a threat and attacks.

Moderna expects the vaccine to be stable at normal fridge temperatures of 2 to 8 degrees Celsius (36° to 48°F) for 30 days and it can be stored for up to 6 months at -20°C.

Pfizer’s vaccine must be shipped and stored at -70°C, the sort of temperature typical of an Antarctic winter. It can be stored for up to five days at standard refrigerator temperatures, or for up to 15 days in a thermal shipping box.

The data from Moderna’s trial involving 30,000 volunteers also showed the vaccine prevented cases of severe COVID-19, a question that still remains with the Pfizer vaccine. Of the 95 cases in Moderna’s trial, 11 were severe and all 11 occurred among volunteers who got the placebo.

Moderna, part of the US government’s Operation Warp Speed program, expects to produce about 20 million doses for the United States this year, millions of which the company has already made and is ready to ship if it gets FDA authorization.

“Assuming we get an emergency use authorization, we’ll be ready to ship through Warp Speed almost in hours,” Mr. Hoge said. “So it could start being distributed instantly.”

The 95 cases of COVID-19 included several key groups who are at increased risk for severe disease, including 15 cases in adults aged 65 and older and 20 in participants from racially diverse groups.

“We will need much more data and a full report or publication to see if the benefit is consistent across all groups, notably the elderly, but this is definitely encouraging progress, said Stephen Evans, professor of pharmacoepidemiology, London School of Hygiene & Tropical Medicine.

The trials were designed to measure whether the vaccines stop people from getting sick rather than whether they prevent transmission, which remains to be tested.

“It is likely that vaccines that prevent symptomatic disease will reduce the duration and level of infectiousness, and thus reduce transmission, but we don’t yet know if this effect will be large enough to make any meaningful difference to the spread of the virus within communities,” said Eleanor Riley, professor of immunology and infectious disease at the University of Edinburgh.

ROLLING REVIEW

Most side effects were mild to moderate. A significant proportion of volunteers, however, experienced more severe aches and pains after taking the second dose, including about 10% who had fatigue severe enough to interfere with daily activities while another 9% had severe body aches. Most of these complaints were generally short-lived, Moderna said.

“These effects are what we would expect with a vaccine that is working and inducing a good immune response,” said Peter Openshaw, professor of experimental medicine at Imperial College London.

The US government, faced with the world’s highest known number of COVID-19 cases, could have access next year to more than 1 billion doses from Moderna and Pfizer, more than needed for the country’s 330 million residents.

The Trump Administration has mainly relied on the development of vaccines and treatments as its response to the pandemic. Moderna has received nearly $1 billion in research and development funding from the US government and has a $1.5 billion deal for 100 million doses. The government has an option for another 400 million doses.

The company hopes to produce between 500 million and 1 billion doses in 2021, split between its US and international manufacturing sites, depending in part on demand.

Europe’s health regulator said on Monday it had launched a real-time “rolling review” of Moderna’s vaccine, as it has done for vaccines from Pfizer and AstraZeneca. Brussels also said it was in talks with Moderna about securing doses.

Other countries such as China and Russia have already begun vaccinations. Russia licensed its Sputnik-V COVID-19 vaccine for domestic use in August before it started large-scale trials. It said on Nov. 11 that its vaccine was 92% effective based on 20 infections in its large trial. — Reuters

ZURICH — Moderna Inc. delivered the latest good news from COVID-19 vaccine developers, saying its experimental vaccine is 94.5% effective in preventing the disease based on interim data from a late-stage trial.

Pfizer Inc. and BioNTech SE on Nov. 9 trumpeted early data indicating their mRNA candidate is more than 90% effective.

A Russian project then touted 92% efficacy for the Sputnik V candidate, named after the Soviet-era satellite, based on a smaller data set.

HOW DO MANUFACTURERS ARRIVE AT EFFICACY NUMBERS?

In Pfizer’s case, it waited until 94 volunteers in its late-stage clinical trial of more than 43,500 people—half got the vaccine, the other half got a placebo—tested positive after developing symptoms.

For 90%-plus efficacy, no more than eight people among those who tested positive had received the vaccine, with the rest having received the placebo.

“Roughly speaking, it’s probably around eight to 86 cases in the treated and placebo groups,” David Spiegelhalter, a Cambridge professor of risk and an expert in statistics, told Reuters. “You don’t need a lot of fancy statistical analysis to show that this is deeply impressive. It just hits you between the eyes.”

Moderna’s interim analysis was based on 95 infections among trial participants who received either a placebo or the vaccine. Of those, only five infections occurred in participants who received the vaccine, which is administered in two shots 28 days apart.

In Russia, Sputnik V-developer Gamaleya Institute reached its preliminary 92% efficacy figure based on 20 illnesses in 16,000 volunteers as its late-stage trial progresses. It aims to reach 40,000 people.

Of the 16,000 people, about a quarter got the placebo.

“It suggests that there is some effect, but it’s insufficient to estimate the magnitude of it,” Mr. Spiegelhalter said.

HOW MANY PEOPLE MUST GET SICK IN BIG VACCINE TRIALS?

Some experts say that, ideally, 150 to 160 people in a trial of tens of thousands of participants must get sick before making a reliable assessment of a vaccine’s efficacy. That’s a bit of a rule of thumb, though, open to interpretation.

“There is no such regulatory standard requiring X number of events for making a reliable decision,” the government-funded Swiss Clinical Trial Organisation said. “The amount of (infections) has to be seen in relation to the disease and its risk profile. It’s rather a case-by-case evaluation.”

Typically, regulators strive to have at least 95% certainty that the trial read-out is not the result of random variations with nothing to do with the tested compound.

For trial sponsors, there is safety in numbers as a large enough trial can ensure that 95% reliability hurdle is cleared.

But the larger the underlying clinical benefit, the fewer trial participants needed to create that clarity.

In Pfizer and BioNTech’s trial, they planned a final analysis when 164 people had become sick, with multiple, pre-planned interim analyses along the way. They skipped an analysis at 32 patients, and once they were ready to release a look at the 62-person mark, 94 had come down sick.

Moderna said it expects to have registered 151 infections when it seeks regulatory approval, meaning the trial will have hit its final endpoint.

Details from the Russian trial are unclear, without access to its protocol.

HOW DO THESE RESULTS STACK UP TO OTHER DRUGS, OR VACCINES FOR OTHER ILLNESSES?

In normal drug trials, for diseases like terminal cancer, benefits of new medicines may be less apparent, with survival benefits of just a few months sometimes revolutionary for patients at death’s door.

For vaccines, however, marginal protection is inadequate, and the World Health Organization ideally wants to see at least 70% efficacy in trials, while the US Food and Drug Administration wants at least 50%.

The efficacy rate reported in the three trials beats those, and appears to exceed that of typical flu vaccines, which the US Centers for Disease Control and Prevention (CDC) estimate reduce the risk of sickness by 40%–60%.

For other shots, the CDC estimates the efficacy of a two-shot measles vaccine at 97%, and a two-dose chicken pox vaccine at 90%. Two doses of polio vaccine are 90% effective, rising to nearly 100% with a third.

CAN WE EXPECT EFFICACY RATES TO HOLD UP AS TRIALS ADVANCE?

Pfizer acknowledged that its final vaccine efficacy percentage may vary. Still, Mr. Spiegelhalter said the study’s design seems likely to generally hold up, based on the 94 sick participants.

“In this case, the effect is so huge, even if there is a little bit of fallback—if the effects become slightly smaller over time—that is very unlikely to be significant.”

WHAT ABOUT REAL-WORLD EFFICACY, SHOULD THE VACCINES BE APPROVED?

The interim data is promising, since it appears to demonstrate that a vaccine can be effective in preventing COVID-19.

The jump to mass vaccinations, however, presents new hurdles, in particular for an mRNA vaccine like Pfizer and BioNTech’s that must be stored and shipped at minus 70 degrees Celsius (-94°F).

The three vaccines so far require two doses. In the Pfizer-BioNTech case, it’s ideally 21 days apart and Moderna 28 days. If people do not stick to the timetable, it may affect the vaccine’s efficacy.

Protection against the mumps, for instance, drops from nearly 90% to 78%, if people don’t get a follow-up shot.

Swiss epidemiologist Marcel Tanner, president of Switzerland’s Academies of Arts and Sciences and one of the government’s top COVID-19 science advisers, expects possible variations in efficacy among older people, whose immune systems wane with time, or those with immune disorders.

“Efficacy says, ‘Does it work?’ Effectiveness says, ‘Can it be applied? Can you carry the efficacy to the people?’” Mr. Tanner said. “But no question: 90% efficacy, at that stage, is a pretty good result.” — John Miller/Reuters