Moderna was the first drug maker to start testing an experimental COVID-19 vaccine on humans. It’s also poised to be the first to enter the final stage of a clinical trial in the United States, on July 27.
But if you’re hoping to soon get the Cambridge biotech’s closely watched vaccine ― or any of nearly two dozen rival vaccine candidates being tested in clinical trials around the world ― don’t roll up your sleeve yet.
The difference between an early-stage trial involving 45 volunteers and a late-stage trial involving 30,000 is, as Mark Twain once characterized another comparison, “the difference between the lightning-bug and the lightning.”
Most experimental drugs and vaccines fail to make it all the way through clinical trials, and there are many unanswered questions about Moderna’s Phase 3 trial, according to experts who weighed in the day after the New England Journal of Medicine reported the vaccine had stimulated a robust immune response in the small Phase 1 trial.
Those questions include whether it will produce similar results in a much larger group of volunteers, how long the immune response lasts, and whether side effects observed in many subjects will remain generally mild. The company has said that some data on how the massive trial is going could be available by the end of the year.
“We must bear in mind the complexity of vaccine development and the work still to be done before COVID-19 vaccines are widely available,” Dr. Penny M. Heaton, chief executive of the Bill & Melinda Gates Medical Research Institute in Cambridge, wrote in an editorial published Tuesday in the journal.
Heaton, an expert on vaccines, delivered the note of caution as the journal reported that the vaccine Moderna developed with the National Institutes of Health spurred immune responses in all 45 healthy subjects who received it in the Phase 1 trial, though it also caused mild side effects in many of them.
The results were impressive, considering that vaccines historically have taken years, if not decades, to develop. The novel coronavirus that caused the pandemic emerged in China only in December. Moderna, a 10-year-old company with no approved products, set a drug industry record by producing its vaccine a mere 42 days after receiving the virus’s genetic sequence.
Unlike traditional vaccines, which use a weakened or killed virus to stimulate an immune response, Moderna’s vaccine relies on genetic material called messenger RNA, or mRNA. The vaccine, now in a larger Phase 2 trial, inserts portions of the coronavirus’s RNA into cells, which then manufacture a piece of the virus to generate antibodies.
No messenger RNA vaccine has ever been approved to prevent any disease, although Moderna is one of several companies seeking to do so with the coronavirus. Other prominent mRNA vaccine candidates include a collaboration between the drug giant Pfizer and the German biotech firm BioNTech. Their vaccine candidate is also expected to enter Phase 3 trials soon.
The Phase 3 trial of the Moderna vaccine will enroll up to 30,000 adults at high risk of contracting the coronavirus, according to the government website clinicaltrials.gov. Half will get an injection containing 100 micrograms of the vaccine and the same dosage 28 days later. The other half will get a placebo.
The website lists 87 trial locations around the United States, including one in Massachusetts, at Brigham and Women’s Hospital. Many of the locations are states where COVID-19 cases have surged in recent weeks, including Florida (six) and Texas (13).
That’s no coincidence. Researchers need to determine whether the vaccine is effective, and the only way to do that is to see how it performs in the real world, where people are getting sick from the coronavirus.
Under the protocol approved by federal regulators, researchers will wait for 56 of the study participants to be diagnosed with COVID-19 and then conduct an interim analysis to determine who got the vaccine and who got the placebo, according to Alan Carr, an analyst at Needham & Co. Researchers will conduct another interim analysis when 106 cases are confirmed, and then a final analysis after 151 cases.
The vaccine will be deemed successful if it prevents 60 percent of infections, Carr said.
Given that the trial hinges on specific numbers of cases at different intervals, it’s impossible to say when researchers will know whether the vaccine is effective.
“But it’s safe to say that if they are able to enroll subjects at sites that are experiencing very high disease rates, this trial will play out even faster,” Carr said.
Carr wrote to investors Wednesday that Moderna previously said that “at least interim data may be feasible” by the end of this year. And if the vaccine is approved by the Food and Drug Administration, the company hopes to deploy it some time next year.
Moderna and its manufacturing partner, Lonza, are already working to produce millions of doses of the vaccine even though it hasn’t been approved. The project has $483 million from the federal Biomedical Advanced Research and Development Authority. It is one of several potential COVID-19 vaccines that have the backing of Operation Warp Speed, a federal government initiative to speed up the development of countermeasures against the virus.
The company believes it can ultimately produce 500 million doses a year, and perhaps as many as 1 billion annually, and has set out to make enough “to be able to vaccinate everybody in the US,” the firm’s chief executive, Stephane Bancel, told analysts Wednesday.
Whether he’s right remains to be seen.
Jonathan Saltzman can be reached at firstname.lastname@example.org