At the end of 2019, before the coronavirus pandemic started, the two best-known faces of the pharmaceutical business were the imprisoned Martin Shkreli and the lawsuit-laden opioid makers at Purdue Pharma LP. The rest of the industry was perhaps best known for the skyrocketing prices of its medicines. In a Gallup Poll of the public’s view of various business sectors, pharma was ranked at the bottom, behind the oil industry, advertising and public relations, and lawyers.
By Drew Armstrong
Source: Bloomberg Businessweek
Reprinted for educational purposes and social benefit, not for profit.
Who’d have guessed that a year later pharma would be getting credit for saving the world? From cruise lines to meatpackers, business will have plenty to answer for in its handling of the pandemic, but this part of it worked. The Covid-19 vaccines developed by the drug industry, in partnership with governments, will almost certainly prevent hundreds of thousands of American deaths and millions more around the world. They will revive trillions of dollars in economic activity, let grandparents see grandchildren, and finally bring an end to a year that has—sing it together one last time as the ball drops over an empty Times Square—really sucked. In a time where almost everything else went wrong, the vaccine effort was something that went (mostly) right.
The quest started in early January, before most people in the U.S. and Europe were even thinking about a pandemic. The biotechnology company Moderna Inc. had downloaded the genetic code for the novel coronavirus from researchers in China. Within a few days, scientists there had developed a vaccine with the U.S. National Institute of Allergy and Infectious Diseases, the research agency led by Anthony Fauci. By mid-March, they’d started a clinical trial.
Pfizer Inc. announced its own plans around the same time. A year and a half before, it had signed a deal with a German biotech company, BioNTech SE, that has similar messenger RNA technology to Moderna’s that could, in theory, rapidly assemble and test new vaccines. Like Moderna, the companies thought the technology could make it possible to quickly turn around a prototype vaccine. “The world hasn’t seen an emergency like this in 100 years,” says Steven Joffe, the interim chairman of the department of medical ethics and health policy at the Perelman School of Medicine at the University of Pennsylvania. “We are lucky in the sense that the science was there.”
Other crucial pieces fell into place behind the scenes. For years the research chiefs of the top pharmaceutical companies have had an annual gathering to talk about ways to speed up their work. As the Covid crisis got worse, about 20 drug companies started a working group with the National Institutes of Health and other government agencies, meeting every other week to look at potential therapies and coordinate clinical trials, says Paul Stoffels, the chief scientific officer at Johnson & Johnson, which has a large-scale Covid vaccine trial expected to produce results in January.
Those efforts would eventually be folded into what’s now known as the Trump administration’s Operation Warp Speed program. Warp Speed was revealed at the end of April, when the pandemic had killed close to 60,000 Americans. The goal was to develop and produce enough shots to inoculate 300 million Americans before the new year. Some companies, including Moderna and J&J, would get direct funding for their efforts. Pfizer got an agreement from the government to buy the vaccine it produced if it worked.
Crucially, the government was shouldering some risk, financing the advance production of the experimental vaccines while clinical trials were still going on. “The most risk-averse people on Earth in the riskiest business on Earth” is how U.S. Health and Human Services Secretary Alex Azar describes the drug industry. “Probably the most common words said in a pharma company are, ‘How do you de-risk this?’ ” Azar, whose department helped oversee Warp Speed, says he understood how tricky a bet on vaccines can be for a business. “These companies are looking at making the multibillion-dollar investments in R&D and manufacturing capacity,” he says. “And they had just been through Zika, SARS, they’ve been through MERS”—viruses for which the pharmaceutical industry investigated vaccines that never saw the outside of a clinical trial before those outbreaks dissipated or were squashed.
The government’s backing let smaller players get in the game and take some riskier technologies forward. Smaller companies such as Moderna “don’t have the resources to do this on their own,” Joffe says of large-scale clinical trials. Pfizer, despite its corporate reputation as a rival-consuming shark, said it would offer up any excess manufacturing capacity it might have—potentially producing competitors’ vaccines.
But even a company of J&J’s size—it reported $15.1 billion in profits last year—needs incentives to rapidly start up a costly vaccine development and testing effort, Stoffels says. Pharma companies could reasonably predict that Covid would be bad and that a vaccine would have a market. “But to mobilize a billion, maybe $2 billion to start manufacturing and do the R&D” is daunting, he says. “While we are big companies, nobody can free up $2 billion in their [profit-and-loss statement] overnight.”
Moderna, AstraZeneca Plc, and other vaccine developers who joined Warp Speed agreed to use similar structures for their clinical trials, so they could easily be compared with one another and so it would be easier to see clear winners. The government also put together a single safety board to oversee them, which Penn’s Joffe sits on. It was an unusual approach, but it let the safety monitors look for worrying side effects or problems that could show up in more than one trial. In usual circumstances, drugmakers might design their experiments to show advantages over competitors’ or dodge a potential head-to-head analysis.
Big Pfizer and tiny Moderna both got their vaccines across the finish line. The shots cleared in December and have been shipped out to states and are now going into people’s arms. Barring surprises, by spring, tens of millions of Americans will have gotten them. By summer, hundreds of millions more will have. It’s an achievement worth celebrating—a shining example of people understanding what their job really is, then doing it. And it’s not a story with a single hero. It’s one about government scientists and private-sector researchers, the trial volunteers who put their bodies on the line, the doctors running the trials, the FedEx and UPS workers making sure the vaccine is delivered during a pandemic winter, the nurses donning PPE to administer the shots, down to the first person being vaccinated after the FDA’s authorization. Go through the chain, and that’s who made this happen.
But it’s also a story that highlights just how badly the U.S. screwed up almost everything else to do with controlling the pandemic. The nation had every asset needed to curb the virus: The world’s best scientists, the biggest collection of biotechnology and pharma companies, a powerful government, and well-established public-health institutions. The U.S. even had unlimited financing. (Perhaps the one other thing policymakers got right is that they pumped enough money into the system to keep the economy alive, but even then Congress was slow to strike a second relief deal, which the president has yet to sign.) And Americans still ended up with a badly contained, deadly outbreak. Schools have gone remote. Lots of restaurants will never reopen. Chances are, you know somebody who was sick enough to be hospitalized or to have died.
Michael Mina, an assistant professor of epidemiology at the Harvard T.H. Chan School of Public Health, believes that cheap, plentiful, rapid tests long ago could have done more to stop the pandemic than just about anything else we’ve done over the past few months while watching cases and deaths stack up and hoping for a vaccine. “The only way to deal with a virus like this appropriately is to try and identify people who are infectious,” he says. He’s helped develop an inexpensive, mostly accurate test with rapid results that can be done on a strip of paper. It’s not as accurate as the diagnostic tests you have to wait hours in line for and often days to get a result back from, but it costs pretty much nothing and is easy to make. “We make more bags of Doritos than I’m asking for,” he says of the number of tests needed. “These are paper strips that get cut from one big piece of paper.”
His idea is that if you test like crazy, you can find enough cases to tell people who are infectious not to be out and about, and you halt a huge amount of transmission. “There are people who aren’t wearing a mask because of politics or whatever,” Mina says. “But they may still not want to get their 80-year-old mom sick at Sunday dinner.” He’s pushed the idea to anyone who will listen, but it would need regulators to sign off, and it’s never gotten off the ground.
So where was the Warp Speed for testing? Fauci, who’s been the face of the U.S. response to the outbreak—or at least the face of what it could have looked like—said at a Dec. 9 event at Harvard’s school of public health that it’s not as if a program of mass, cheap testing would have been impossible to achieve. “We have done things infinitely more complicated than that,” he said. “We have the technology. We can do it.”
Which, when you think about it, brings up more questions. Where was the Warp Speed for contact tracing? For public-health measures? For data? For making sure health-care workers had protective gear? Where was the Warp Speed for keeping open businesses, churches, and schools? For everything that went wrong, where was that combination of leadership and industry and money that could have made it go right? While we’ve been marveling, rightly, at the science that’s made a vaccine possible, most of that other stuff never got going at the same level.
HHS Secretary Azar says there was a national strategy for much of this—it just wasn’t as visible as Warp Speed. But we’re still facing a tough winter even with large-scale vaccination efforts on the horizon. Tests are more common now but hardly plentiful, at least not in the volume you’d need to truly use them for broad, constant public-health surveillance, the kind that would allow people en masse to go to school or work, travel on airplanes, or attend concerts or sporting events. In the New York City suburb where I live, my wife and I spent days trying to book a just-to-be-sure Covid test before we headed south to visit relatives for Christmas. As I’m filing this to my editor, we’re barreling down the interstate with plans to eat food out of a cooler, pee on the side of the road, and brave 14 hours in a midsize SUV with two small children—one of whom is disastrously vomit-prone—all to preserve the little bubble of isolation we’ve kept up ahead of the trip.
Even the uncomplicated things have been hard for much of the country. Not wearing a mask is seen as a political act by a significant portion of the population, unhelped by a mixed message from government leaders, some of whom have suggested that, basically, masks are for losers. “We love to inject ourselves with stuff, but when it comes to simple messaging about health, doing something that would help people, we hate it,” Mina says. “We are very willing to mop up messes, but we have no willingness to stop them before they occur.”
There is one more opportunity to get a big thing right. The U.S. gets credit for having pushed the development of the vaccines. Now it has to make sure people take them.
First, the government has to guarantee there’s enough vaccine. That was a key part of the goal of Warp Speed. Since the program started, the U.S. has signed deals for enough shots to cover 555 million people, with the option to buy more. But it has only enough from Pfizer, so far, for 100 million. And from Moderna for 100 million. Other vaccines it’s made deals for, such as AstraZeneca’s and J&J’s, are still in development.
There are growing concerns that the U.S., after leading development of vaccines, may not get them as fast as it had hoped. Instead of 300 million covered by the end of 2020, the U.S. is now aiming to supply vaccine for 20 million people by the end of December and getting to a total of 100 million by the end of February. Vaccinating all of America now looks more like an end-of-2021 goal.
Even if there is enough vaccine, of course, people have to be willing to take it. “If we have a 95% effective vaccine and only 40% to 50% of the people in society get vaccinated, it’s going to take quite a while to get to that blanket of herd immunity that’s going to protect us,” Fauci said at the Harvard event.
Early on in the development of the vaccines, there was debate about whether to run what are known as challenge trials. In these, healthy volunteers get an experimental vaccine and are deliberately exposed. It’s an ethical razor’s edge. Is it moral to give somebody a virus you know kills a small percentage of patients, with their best defense being a vaccine that isn’t known to work? Because there weren’t Covid therapies that could cure an infected patient, researchers passed on the idea. It wasn’t worth the chance that someone could die.
Instead, the vaccine trials signed up tens of thousands of volunteers, split into those who got the real shot and those who got a placebo. To find out if the vaccine was effective, they had to go back out into the real world and bump into the virus on their own. The idea with these large trials—the gold standard for testing a vaccine’s efficacy and safety—is that if the vaccine works, Covid-19 cases rapidly accumulate in the group that got the placebo but not in those who got the real thing. Get enough cases, and you can perform a statistical analysis of exactly how effective the vaccine is. But if there isn’t enough virus circulating, few in the trial get infected, and results take longer.
Over the summer, Pfizer’s and Moderna’s trials went into lulls as the pandemic waned. Then in the fall, cases exploded—millions of infections were tallied around the country and thousands of people died—and the results started pouring in on the trials. J&J said in December it would shrink the size of its 60,000-person trial because the cases were coming in so fast. The U.S., because of its failure to control the pandemic, had essentially created one big challenge trial.
“There is an irony and a situation that we all hoped wouldn’t have occurred,” U.S. Food and Drug Administration Commissioner Stephen Hahn says. “The number of cases did help expedite the performance of clinical trials, both here and abroad. That did help us get to this point. But I think none of us would have wanted it to be that way.”
That’s the contradiction of the U.S.’s vaccine success. The government and scientists all working together came up with a shot to save the world—and then they were able to prove so quickly that it worked only because those same institutions couldn’t save us from ourselves. —With Robert Langreth