For the pharma behemoth Pfizer, the race to develop a Covid-19 vaccine is not just about bringing a quick end to the global pandemic. It’s also about the company’s reputation among scientists, politicians, and the public, and it’s about pride: demonstrating that one of the world’s biggest drug makers is as nimble — and more formidable — than any upstart biotech.
Pfizer and that upstart rival, Moderna, were the first companies to launch large clinical trials to prove their vaccines’ efficacy, and on the same day: July 27. They have been in a neck-and-neck competition ever since.
But Pfizer is counting on one scientist to give it an edge: Kathrin Jansen.
The company’s head of vaccine research and development, Jansen, 62, has led the development of the world’s two best-selling vaccines, against human papilloma virus and pneumococcus, at two different companies. Since March, when Pfizer partnered with the German startup BioNTech to develop a vaccine against Covid-19, Jansen has led a 650-person team night and day on Zoom meetings from her Manhattan apartment, occasionally making the trip to Pfizer’s vaccine headquarters in Pearl River, N.Y.
“I stay out of the way,” she told STAT, “because I’m not needed in the laboratory.”
Not everyone would agree. In the words of Pfizer R&D chief Mikael Dolsten, Jansen is the personification of the company’s urgency to take on the “terrifying pandemic.” On daily calls with Dolsten and the team at BioNTech, she has plotted the company’s massive effort: testing four different potential candidates, catching up with Moderna and its partner the National Institutes of Health, which were originally on a faster time path, and making sure that the odds of success were as high as she could humanly make them.
For all the pressure, William Gruber, a longtime Pfizer vaccine executive, said of Jansen: “She will not sacrifice quality for speed. In other words, it’s got to be right.”
He said, “She is really a hard-nosed scholar of vaccine development.”
Now, Jansen and her industry are being put to the test, as the world is desperate for a weapon against the pandemic. It could even be a big business, worth many billions of dollars a year, especially if efficacy wanes and booster shots are required. Developing a vaccine this fast has never been attempted. But Jansen is known for her calm but commanding manner and devotion to data over groupthink.
Her journey thus far holds clues as to whether any of the current vaccine efforts will succeed.
“She’s exactly who you want in that position,” said Paul Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia. She fights for the vaccines she thinks are important, he said. “People who think pharmaceutical companies are evil should spend time with people like Kathrin Jansen.”
How soon will we know what comes of all this round-the-clock development of a vaccine? Answers could come earlier than many people expect — even next month.
Like their rivals, Pfizer and BioNTech are conducting their 30,000-patient study based on guidance from the Food and Drug Administration that aims to be absolutely certain a new vaccine is safe and reduces the total number of infections by about half.
But researchers are hoping their shots will be more effective than that, and have built into the studies what are known as ‘’interim analyses,’’ which means a group of researchers monitoring the studies can look at the data early as soon as a certain number of people develop Covid-19.
For Pfizer, the first look could occur as early as September, when there are 32 cases of the disease in the study. Another will happen at about double that. If the vaccine were to turn out to reduce infections by 80% or 90%, that might be enough to show it is effective. The question then: Would there be sufficient safety data for regulators to take action, perhaps making the vaccine available to people at high risk, like nursing home workers or people in heavily affected communities?
Jansen’s 36-year career has led to this moment. Her fascination with medicines began when she was a small child in East Germany. She caught frequent throat infections and coughs. Her father, a chemical engineer, would always have a treatment — an antibiotic, a codeine suppository — at the ready. “You’re a small person and you have this violent cough and you feel sick as a dog,” she remembered. “And then you get this drug. And it makes you feel better.”
Shortly before the construction of the Berlin Wall in 1961, Jansen’s family fled to West Germany. Her father was comfortable in his career. Her mother “saw the writing on the wall,” Jansen said. Kathrin was “appropriately drugged” so she wouldn’t say the wrong thing to authorities, and the family left everything they had behind, driving in three cars. An aunt drove Kathrin, and her father claimed he had a job interview.
“I cannot imagine what the future would have been if that decision would not have been made,” she said.
As a graduate student, Jansen learned the scientific value of failure the hard way. Finishing her Ph.D. thesis at Philipps-University in Marburg, she believed she had discovered a new chemical pathway in bacteria. Then she did one final experiment — and her results fell apart. It wasn’t a new chemical pathway, but an old one that evolution had learned to use in a clever way.
Distraught, she went to her thesis adviser and mentor, and was met with an amused smile. It was a lesson: Science is not predictable, and often “eureka” moments collapse in the face of new data. It was an especially apt lesson for someone who would work in drug development, where more than 90% of all medicines that start human studies fail.
After earning her Ph.D. in 1984, Jansen worked at Cornell and Massachusetts General Hospital before moving to the Glaxo Institute for Molecular Biology in Geneva to focus on drug development. When she moved back to the U.S. in 1992, a friend from Glaxo, Alan Shaw, who was now at Merck, listed a job opening at the company’s vaccine division, where the standard inoculations against measles, mumps, and hepatitis B were developed.
Merck executives were rumored to be toying with the idea of halting their vaccine research. Shaw was looking for a way to transition his scientists toward developing other types of drugs, and wanted Jansen to work on a project in diabetes. He hired her; she quickly got the project killed. “We couldn’t reproduce a single thing that was described,” she said.
What did grab her attention was an idea that many of Jansen’s colleagues would view as crazy.
Jansen fell in love with making vaccines. Her first target: the human papilloma virus, which had been shown to be the cause of cervical cancer in the 1980s. HPV-caused cervical cancer afflicts 600,000 women worldwide, killing half of them, each year. Before Pap tests became common in the U.S., it was the most common cause of cancer death in women in the country.
Shortly after Jansen arrived at Merck, researchers there came upon an idea for a vaccine: Two researchers at the University of Queensland, Jian Zhou and Ian Frazer, had discovered that if the proteins from the human papilloma virus, or HPV, were made using biotechnology, they self-assembled into “virus-like particles” that could serve as the basis for a vaccine. Jansen was fascinated. She seized on the idea of making the vaccine in genetically modified yeast, just as Merck already did with its hepatitis B vaccine, a shot that was originally controversial because the disease is sexually transmitted. (Now, that is the first shot babies receive because it gives lifelong protection against a type of liver cancer.)
Edward Scolnick, who ran Merck’s research labs from 1985 until 2002, was initially not sold on the idea when Jansen and several other researchers came to his office with it. Another company’s experimental vaccine against herpes had just failed. Why, he asked, would an HPV vaccine work when the herpes vaccine hadn’t?
The case against the vaccine was obvious. Sure, the hepatitis B vaccine had worked out great. But HPV couldn’t be cultured in the laboratory, so scientists could not directly study it. Worse, this meant even if the Merck scientists could show that they could create antibodies against the virus-like particles they were making in yeast, they couldn’t see if those were what are known as neutralizing antibodies, the type that actually stop the virus from reproducing.
Scolnick asked for a pile of scientific papers to read, and asked to meet again in a week. When they returned, he announced to his colleagues that he was on board. His one concern was whether the team could develop assays to show if the vaccine was working in trials, so it would not be flying completely blind. We’ll make the assays, Jansen told him. Scolnick became the project’s defender.
“She is fearless at taking on any project that she thinks is important, and is not afraid to plunge in and figure out what needs to be done,” Scolnick said. “In industry, that is not always the case, because many projects fail and people in that setting worry about their job. Whether they’ll be demoted, fired, passed over. She just doesn’t think about that.”
Even with Scolnick’s support — and that of Jansen’s other scientific bosses — Jansen was faced with an unrelenting barrage of skepticism. The company’s bean counters thought the project was worth less than nothing, actually reducing the amount of money on the company’s balance sheet. And many other researchers thought it would never work.
After a tense debate at one meeting, Jansen says a senior medical researcher cornered her in the hallway. “All of a sudden, he started yelling at me at the top of his lungs.” She let him blow off his head of steam, and then told her superiors that she was not to be treated in that manner.
In 2002, a trial of 2,400 women, published in the New England Journal of Medicine, showed a vaccine against one strain of HPV, HPV 16, prevented infection with that strain 100% of the time, providing a proof of concept. Gardasil was approved in 2006, based on studies involving 21,000 girls and women. Before that happened, Jansen left Merck, confident the product would succeed.
“If you have a scientific intuition and you’re careful with your experimentation, at the end, you have to follow your gut and not let naysayers derail you,” Jansen said.
Scolnick said Jansen should have been put in charge of Merck’s vaccine work, but she wasn’t. Two decades later, now the chief scientist emeritus of the Stanley Center for Psychiatric Research at the Broad Institute, he still has confidence in his former protege. He praises Jansen for the speed and quality of studies on the Covid-19 vaccine, and Pfizer for funding all the work itself, without government grants.
“They’re going to win the race,” Scolnick said of Pfizer. “They’re going to have the first vaccine in the U.S.”
From the Gardasil triumph, Jansen leapt into the arms of disaster.
“I just wanted to explore learning, and be responsible for more than just the research aspect,” she said. So in October 2004, she took a job as the chief scientific officer of a company called VaxGen, then best known for a failed HIV vaccine. In the wake of the bioterror scares that followed the Sept. 11 attacks, the company was awarded an $877.5 million contract by the U.S. Department of Health and Human Services to provide 75 million doses of an anthrax vaccine. But VaxGen failed to be ready to start manufacturing on time because it couldn’t keep the vaccine chemically stable. Jansen left in July 2006. That December, HHS canceled the contract.
Once again, Jansen’s next step came from a past connection. Emilio Emini, an old boss from Merck, had taken the top vaccine job at Wyeth, a company with a long history of making childhood vaccinations. He called Jansen on the phone, then took her out to dinner. He needed her help with one of Wyeth’s crown jewels: a vaccine called Prevnar.
“It was evident I needed some pretty heavy duty scientific expertise.” Emini told STAT.
In 2000, Wyeth had launched a vaccine called Prevnar 7, a tremendous medical and commercial success. By linking sugars to the outside of proteins found on the surface of a bacterium called pneumococcus, the company had created a vaccine that produced a strong antibody response in children. In the seven years after Prevnar 7 was introduced, the rate of pneumonia, bloodstream infections, and meningitis caused by the pneumococcus bacteria in kids under 5 had plummeted 80%.
But Prevnar 7 only gave kids immunity to seven strains of pneumococcus. Other previously rare strains, including a virulent one called 19a, were starting to fill the gap. So Wyeth was developing a newer vaccine, Prevnar 13, that would protect against 13 strains. But each strain added complexity, and Prevnar 13 was the most complicated vaccine ever made.
Many of the basic processes needed to cross the finish line were missing. Shortly after joining, Jansen remembers turning to Emini and saying, “Did you have any idea how bad the situation was?” Emini’s response, now: “I’ll be honest with you, I don’t think we’d have been able to do it successfully without Kathrin.”
The problems were with the assays needed to measure if this soup of proteins and sugars was always up to specifications, and if it was creating the right reactions in patients in clinical trials. The process of developing them was painstaking.
When Pfizer purchased Wyeth for $68 billion in 2009, the vaccine group was sheltered from disruption. That was largely for three reasons: Pfizer lacked a large vaccine effort of its own. Prevnar 13 was set to become a financial success. And Dolsten, who had worked at Wyeth, emerged as the R&D head of the combined company. Prevnar 13 was approved for children in 2010 and to prevent pneumonia in older adults in 2012. The vaccine is Pfizer’s best-selling product and the best-selling vaccine in the world, with annual sales of $5.8 billion in 2020. Pfizer is currently working on a version with 20 strains.
After the vaccine was approved, Emini left to run global vaccine development at the Bill & Melinda Gates Foundation, a dream job for him, and one he said he wanted to do before he got too old. Jansen succeeded him as head of all of Pfizer’s vaccine research.
Jansen’s role at Pfizer is not only to come up with the next, lucrative iteration of Prevnar, but also to press forward on new vaccines. She’s taken on hard targets: respiratory syncytial virus, the top reason infants are hospitalized; and two drug-resistant bacteria, staphylococcus aureus and clostridium difficile.
This hasn’t led to any big victories yet. In December 2018, Pfizer said a study of Pfizer’s attempt at a staphylococcus aureus vaccine — a target Jansen had pursued since her days at Merck — had been stopped because there was no chance the vaccine would beat placebo. Pfizer is no longer developing the vaccine.
The company’s Covid-19 efforts grew out of its work in something far more mundane: trying to create a new type of influenza shot. In August 2018, Pfizer paid BioNTech $120 million —- with the potential to pay another $305 million, plus double-digit royalties — to create a new flu vaccine.
It was a step into working with a bold new technology: mRNA.
This substance, known as messenger RNA, is the genetic messenger that the body uses to turn DNA code into proteins. Get it into a cell, and it should turn it into a protein factory. That could be used to turn cells into drug — -or vaccine — factories. The idea was to use this tech to replace the slow and somewhat haphazard method used to produce flu shots in chicken eggs or, sometimes, in insect or other cells.
Moderna, based in Cambridge, Mass., has made the biggest headlines in the mRNA field, raising a stunning $3.9 billion, according to Pitchbook, from private and public markets. Pfizer’s partner, BioNTech, was founded by a Turkish-born oncologist, researcher, and entrepreneur, Ugur Sahin.
Jansen and Sahin were instantly simpatico. “Some people you just immediately have a good relationship,” she said. They corresponded for months before Sahin flew to Pfizer’s headquarters in person to meet with Jansen and Dolsten when the final deal was signed.
When SARS-CoV-2 began spreading more widely in February — potentially airborne, contagious, but more deadly than influenza — Sahin was immediately worried. It had the markings of a pandemic. He pushed his team to come up with potential vaccines. When he thought his team had something, he called Jansen. Would Pfizer want to work on vaccine with BioNTech? “Of course,” Jansen said. She told him she had been about to call herself.
Pfizer and BioNTech decided to test not one but four potential mRNA vaccines that used different ways of chemically preparing the mRNA and the particle of fats it must be encased in so the body doesn’t destroy it. All four, like all the Covid-19 vaccines in clinical development, are based around the spike protein, which the virus uses to hijack its way into human cells.
The companies released data on one vaccine, based on the part of the spike protein that grabs the cell the virus is entering, on July 1. Data for a second, containing the full spike protein, was released Aug. 20 — and showed it had fewer side effects. That is the one being studied in the giant study design to prove it prevents infection.
Although both the Moderna and Pfizer-BioNTech vaccines use mRNA, the technology has never been used in an approved drug. Other companies, with their own technologies, are in hot pursuit. AstraZeneca, Johnson & Johnson, Novavax, and Sanofi will start their own giant trials in short order this fall. Experts hope that, to fill the global need, they all work.
Jansen is confident. There’s not enough data to tell how the vaccines will compare. All of these vaccine efforts produce antibodies against SARS-CoV-2, but no one knows what antibody levels are needed to protect people from infection.
Jansen notes that, in early trials, the Pfizer-BioNTech shot also seems to rev up two types of white blood cells: those that detect the virus of the immune system, and those that kill cells once they are infected. If the virus is “wimpy,” she says, the antibodies could be enough. But those extra lines of defense are nice to have.
She says that the skepticism reminds her of the skepticism about Gardasil all those years ago.
“There were many people who thought this couldn’t work, and of course, they were wrong,” she recalled.
She hopes the same is true now. So does everyone else.