The New York Times, September 23, 2020 (with Katie Thomas)
The feverish race for a coronavirus vaccine got an infusion of energy on Wednesday as Johnson & Johnson announced that it has begun the final stage of its clinical trials, the fourth company to do so in the United States as the country hits a grim milestone of 200,000 deaths from the pandemic.
Johnson & Johnson is a couple of months behind the leaders, but its advanced vaccine trial will be by far the largest, enrolling 60,000 participants. The company said it could know by the end of this year if its vaccine works.
And its vaccine has potentially consequential advantages over some competitors. It uses a technology that has a long safety record in vaccines for other diseases. Its vaccine could require just one shot instead of two — important considering that the entire population of the world needs vaccination. And it does not have to be kept frozen as it is delivered to hospitals and other places where it will be given to patients, simplifying the logistics of hundreds of millions of doses.
“Big news,” President Trump tweeted about the trial on Wednesday morning. “@FDA must move quickly!” he added, referring to the Food and Drug Administration, which oversees vaccine approval.
The president has repeatedly claimed that a vaccine will be ready before Election Day on Nov. 3, and urged federal regulators to act quickly to approve one, raising fears that they will bow to the pressure and rush their vetting process. The federal government’s Operation Warp Speed program has invested more than $10 billion in private companies’ coronavirus vaccines to date, including about $1.5 billion to Johnson & Johnson to develop and manufacture its vaccine.
Facing criticism over secrecy, several companies — including Johnson & Johnson on Wednesday — have taken the rare step of releasing the detailed blueprints of their trials, which are typically considered proprietary. And the F.D.A. is expected this week to release stricter guidelines outlining the criteria it will use to vet clinical trial data.
Never in history has a vaccine been tested and manufactured so quickly — in months instead of years. Right behind Johnson & Johnson are Sanofi and Novavax, which may prove just as good or better than the leading contenders.
“We need multiple vaccines to work,” said Dr. Dan Barouch, a virologist at Beth Israel Deaconess Medical Center who led the development of the technology used in Johnson & Johnson’s trial. “There are seven billion people in the world, and no single vaccine supplier will be able to manufacture at that scale.”
Johnson & Johnson’s advanced trial, known as a Phase 3 trial, started on Monday. At a news conference, Dr. Paul Stoffels, the company’s chief scientific officer, said the company might be able to determine by the end of the year if the vaccine is safe and effective. The company will soon be posting a manuscript online with data from the earlier phases of its trials, he said.
Johnson & Johnson has begun manufacturing the vaccine on an industrial scale to build up a supply that can be released immediately if the vaccine is authorized, Dr. Stoffels said in an interview on Wednesday. He expected to have tens of millions of doses ready by the end of the year. “Then we can ramp up to many more batches,” he said.
Johnson & Johnson’s vaccine uses an adenovirus to carry a gene from the coronavirus into human cells. The cell then produces coronavirus proteins, but not the coronavirus itself. These proteins can potentially prime the immune system to fight off a later infection by the virus.
Adenovirus vaccines must be kept refrigerated but not frozen, unlike the two front-runner vaccines, by Moderna and Pfizer, which depend on bits of genetic material known as mRNA. The freezing requirement could make the distribution of those vaccines difficult, especially to places without advanced medical facilities.
Moderna and Pfizer’s vaccines also require two jabs given a few weeks apart, a significant logistical hurdle.
“It would be fabulous if we had something at a single dose,” said Dr. Judith Feinberg, the vice chairwoman for research in medicine at West Virginia University, who was not involved in the study.
No one will know if the single jab works until the Phase 3 trial is over, Dr. Feinberg said. But if it worked, the single dose could greatly speed efforts to curb the pandemic.
“The real issue here is time,” she said. “We’ve got to vaccinate a lot of people really quickly.”
The adenovirus vaccine technology used in Johnson & Johnson’s trial was developed by Dr. Barouch in the early 2000s. The company acquired it and used it to make vaccines for Ebola, H.I.V., respiratory syncytial virus and Zika. All told, 100,000 people have received the adenovirus vaccine in clinical trials for those four diseases, without any serious side effects.
Johnson & Johnson’s Ebola vaccine was licensed in Europe in June. In contrast, the designs for the other three coronavirus vaccines in Phase 3 trials in the United States have not yet been licensed to treat any disease. (A different kind of adenovirus is being used in AstraZeneca’s coronavirus vaccine trials, which have been paused in the United States because of safety concerns.)
Accustomed to the typically slow pace of vaccine research, Dr. Barouch has been astonished by the past eight months of swift work on the coronavirus vaccine.
“It’s pretty amazing,” he said in an interview. “We never would have thought it could be done that quickly.”
Dr. Barouch and his colleagues carried out experiments on animals to learn how the vaccine stimulates the immune system to fight the virus. In one critical experiment, results of which were published in July, they found that the vaccine gave monkeys enough antibodies to protect them from an infection with the coronavirus.
After these promising results in animals, Johnson & Johnson began small safety studies in people, known as Phase 1 / 2 trials. Dr. Stoffel said that an analysis of 395 of the volunteers had found no serious side effects. And they produced encouraging levels of antibodies even after just one shot, he said.
“The single dose could be sufficient to protect people for a long time,” he said.
A Phase 1 / 2 trial measures immune responses but cannot determine if a vaccine actually protects against a virus. Dr. Barouch noted that a single dose of the vaccine produced a level of antibodies in people that his previous experiments showed was enough to protect monkeys.
The company is planning to recruit up to 60,000 people over the age of 18 for its Phase 3 trial in the United States, Argentina, Brazil, Chile, Colombia, Mexico, Peru and South Africa.
The trial is about twice as big as Moderna’s, and significantly larger than Pfizer’s. This month, Pfizer announced it planned to increase its trial to 44,000 people from 30,000.
Dr. Barouch said the larger size would provide a better sense of the safety of the vaccine and might also reduce the time it takes to determine if the vaccine is effective. “It will provide for a faster readout,” he said.
Johnson & Johnson posted the trial blueprints, known as a protocol, on its website on Wednesday, following the lead of its competitors, which did so after independent researchers called on the companies to be more transparent. The protocol showed that the trial’s goal is to measure whether the vaccine shows 60 percent efficacy after 164 participants develop Covid-19.
An outside review board can begin evaluating the results for efficacy after 20 people have become sick, and then the board will check in at least once a week after that, the protocol stated. Dr. Stoffels said that the trial would not be stopped early unless there is overwhelmingly positive data on safety and effectiveness, and the data include sick people in high-risk populations — such as older people. Pfizer’s plan allowed an outside board to check the data for early efficacy four times, beginning after 32 participants have developed Covid-19. Moderna’s allowed for two early looks, starting after 53 cases.
Johnson & Johnson will be testing the single dose in the 60,000-person trial and also run a smaller trial using a double dose.
But Dr. Barouch warned that Phase 3 trials results can’t be pinned to a fixed date. If the trial takes place where there are relatively few cases, it will take longer before enough people get Covid-19, the disease caused by the coronavirus, to know that it works. “It depends on where the epidemic goes,” he said.
Copyright 2020 The New York Times Company. Reprinted with permission.