The Captain of Operation Warp Speed

By Allysia Finley, WALL STREET JOURNAL  10-9-20

If Covid-19 is a once-in-a-century pandemic, the timing could be a lot worse. A lockdown would have been far more burdensome before the internet made it easier to work, meet and shop at home. And thanks to other technological breakthroughs, vaccines may be universally available as early as next fall.

Past vaccines have taken a decade or longer to develop, and more than half over the past 20 years have failed during clinical trials. But four vaccine candidates have entered the last phase of clinical trials before approval by the Food and Drug Administration. Technological breakthroughs that were already in progress got a boost from a bureaucratic one in May, when the Trump administration launched “Operation Warp Speed.” The initiative organized government agencies and private companies around the goal of developing, manufacturing and distributing hundreds of millions of vaccine doses with initial doses available by early 2021.

Leading the operation is Moncef Slaoui, a Moroccan-born Belgian-American scientist who shepherded vaccine development at the U.K. drugmaker GlaxoSmithKline from 1988 to 2017. His interest in immunology and vaccine development is personal: When he was growing up in Casablanca, his younger sister died of whooping cough. He earned a doctorate in molecular biology and immunology at the Free University of Brussels, then immigrated to the U.S. for postdoctoral work at Harvard and Tufts medical schools.

In 1988 he landed a job in GSK’s vaccine division. There he helped develop one of the world’s thickest vaccine portfolios, including inoculations for meningitis, human papillomavirus and rotavirus. The company developed 14 successful vaccines during Mr. Slaoui’s tenure. When the Trump administration tapped him to run Operation Warp Speed, liberals predictably criticized him because he came out of private industry.

Mr. Slaoui, 61, notes that vaccine development entails many dead ends but also plenty of important discoveries and lessons along the way. He worked on a vaccine for genital herpes and a universal flu shot for every strain of the virus, both of which failed. But sometimes the results are worth the wait. GSK’s malaria vaccine was approved in 2015 by the European Medicines Agency after more than a quarter-century of research and development.

“In the process of discovering these vaccines that either didn’t work or took forever,” he says, “what we did was learn.” Scientists now have a far better understanding of how to design vaccines based on the “kind of immunity defense we need, which is different from one pathogen to another.”

All vaccines aim to stimulate a durable immune response that prevents future infection and illness. Many familiar vaccines, such as those for polio, smallpox and MMR (measles, mumps and rubella) use an attenuated or inactivated virus that stimulates the production of antibodies without causing a dangerous infection.

But in recent years vaccine makers have developed “platform” technologies that can be tweaked to different pathogens. “The technology is like a cassette player, and you put a different cassette in it and you listen to different music,” Mr. Slaoui says. “There are like five or six different platform technologies, and you can test them all in parallel against a particular pathogen by simply putting a piece of the genes from the pathogen within that platform technology. And that allows you to select quite quickly a candidate that you can take into development.”

Example: Moderna’s and Pfizer’s Covid vaccines use mRNA platforms, which program human cells to produce a protein that resembles the “spikes” found on the surface of coronaviruses, through which they bind to cells. This doppelgänger prompts the body to produce antibodies that will attack the real virus. Moderna is also using its platform to develop vaccines against cytomegalovirus, Zika and some cancers.

Adenovirus-vector vaccines by AstraZeneca and Johnson & Johnson work somewhat differently. They use a genetically engineered virus that carries the genetic code to create coronavirus spike proteins in human cells, which tricks the body into producing antibodies against Covid. Johnson & Johnson this summer received approval from the European Commission for an adenovirus-based Ebola vaccine.

Operation Warp Speed has invested in six vaccine candidates (Moderna, Pfizer/BioNTech, Johnson & Johnson, AstraZeneca, Novavax, and Sanofi /GSK) with the hope that at least a couple will prove safe and effective in clinical trials. “What was extremely useful in the case of the Covid program,” Mr. Slaoui says, “was to frankly use judgments and experience to say, ‘OK, there are four platform technologies that are best suited to, A, be successful, B, make the timeline, C, be manufacturable at scale. And D, we can have access to them.’ ”

Pharmaceutical development is a costly business with an uncertain reward. Operation Warp Speed attenuates the risk by providing vaccine makers $10.7 billion up front to support clinical trials and development. “For the companies it became exclusively a matter of opportunity cost of the teams enrolled in the work, if they were working on some other program,” Mr. Slaoui says.

The operation has also speeded up the testing process that leads to FDA approval. Four of the six vaccine candidates have already proved safe and effective in the first two trial phases, which test whether the inoculations produce what are known as neutralizing antibodies. They now move on to Phase 3, which involves inoculating tens of thousands of subjects at different locations with either the vaccine or a placebo, then tracking them over several months.

The trials, Mr. Slauoi emphasizes, are run “absolutely as usual.” The improvements in speed come from administrative streamlining. Vaccine makers have been able to do in six to seven months what would usually take six or seven years by eliminating what Mr. Slaoui calls “dead time” between phases—for instance, by preparing trial sites and recruiting volunteers in advance. “As soon as [vaccines] were in technical work, so still in the lab and in animals, we already were preparing the sites for the Phase 1 trial, but also, critically, for the Phase 2 and Phase 3 trials.”

Results are analyzed instantly. “The reports are prewritten without the data, so that when the data comes, the framework of the report is ready—of course interpreted based on the data and the science,” he says. Vaccine makers then “submit the reports to the FDA, the FDA looks into them—maximum one week—and gives the green light to go into [the next phase] depending on the technology and the level of comfort with performance of the vaccine in the studies.”

Democrats have stoked anxieties that the administration will push through an unsafe vaccine for political purposes before the election. “If Donald Trump tells us that we should take it, I’m not taking it,” Kamala Harris said during Wednesday’s debate. But a pre-election vaccine became impossible this week when the FDA published guidelines that require vaccine makers to follow trial participants on average two months after their final injection before seeking emergency use authorization.

Suspected side effects can delay approval even when they aren’t caused by the vaccine. Serious health conditions regularly happen during vaccine trials, Mr. Slaoui says. But they also happen in the general population. Vaccine trials are supervised by independent safety boards, which investigate such adverse events. AstraZeneca halted recruitment for its Phase 3 trial in the U.S. last month after a U.K. participant developed transverse myelitis, a rare spinal-cord inflammation. The company concluded there was insufficient evidence to tie the condition to the vaccine.

Vaccine approval also depends on the vagaries of the epidemic itself. “We try to localize the clinical trial sites in the cities and the townships where there’s a lot of transmission,” Mr. Slaoui says. But that’s a moving target. The FDA requires that a vaccine be shown to be at least 50% more effective than a placebo in preventing Covid-19. That threshold takes longer and becomes harder to meet if infections in the general population slow.

So he hesitates to predict when a vaccine will be approved or become available to the public: “It’s extremely unlikely that is achieved in October; it’s slightly more likely in November, it’s more likely in December, and it’s really, really likely in January. Where it’s going to be, I don’t know; nobody knows.”

But he adds a promising note: The two mRNA vaccines by Moderna and Pfizer, which are furthest along in clinical trials, seem to work well in older people. “That, to me, is very, very reassuring, because that’s the highest hurdle.”

Operation Warp Speed, meanwhile, also looks past approval to manufacturing and distribution. It has funded the manufacturing in advance of hundreds of millions of doses of the vaccine candidates and is working to ensure that vaccines are seamlessly distributed to doctors’ offices and pharmacies once they’ve been approved.

“In contrast to testing, where we didn’t know before the month of March or April how to distribute tests to every spot in the U.S., we know how to distribute vaccines to every spot in the U.S.,” Mr. Slaoui says. “It happens every year for flu and shingles.” But unlike flu shots, some Covid-19 vaccines will require “deep freezing.”

Tracking systems will have to be “incredibly precise” to ensure that patients each get two doses of the same vaccine and to monitor them for adverse health effects. Operation Warp Speed has selected the medical-distribution company McKesson and cloud operators Google and Oracle to collect and track vaccine data.

What lessons has Mr. Slaoui learned while leading Operation Warp Speed? For one, he jokes, not to have a pandemic during an election year. “Politicizing vaccine development is a bad idea. Across the line I think there has been too many question marks during the process,” he says. “I hope that anxiety disappears as the vaccines become available and the data is transparent.”

“On the manufacturing side,” he says, “we have learned a lot to scale up some technology.” He also suggests that the FDA could accelerate vaccines for other diseases by approving experimental platform technologies that have proved safe in Covid-19 trials. This would drastically reduce cost and increase speed.

“One of the remarkable features of Operation Warp Speed is the collaboration and partnership between government entities and industry,” he says. With politicians so often at loggerheads with the pharmaceutical industry, this may be as important a breakthrough as any vaccine.

Ms. Finley is a member of the Journal’s editorial board.

October 10, 2020 | Comments »

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