Countries, firms risk billions in race for virus vaccine

NEW YORK: In the race to develop a vaccine to end the COVID-19 pandemic, governments, charities and Big Pharma firms are sinking billions of dollars into bets with extraordinarily low odds of success.

They’re fast-tracking the testing and regulatory review of vaccines with no guarantee they will prove effective. They’re building and re-tooling plants for vaccines with slim chances of being approved. They’re placing orders for vaccines that, in the end, are unlikely to be produced.

It’s the new pandemic paradigm, focused on speed and fraught with risks. “The crisis in the world is so big that each of us will have to take maximum risk now to put this disease to a stop,” said Paul Stoffels, chief scientific officer at Johnson & Johnson , which has partnered with the US government on a $1 billion investment to speed development and production of its still-unproven vaccine. “If it fails,” Stoffels told Reuters, “it will be bad.”

Historically, just 6% of vaccine candidates end up making it to market, often after a years-long process that doesn’t draw big investments until testing shows a product is likely to work. But the traditional rules of drug and vaccine development are being tossed aside in the face of a virus that has infected 2.7 million people, killed more than 192,000 and devastated the global economy. With COVID-19, the goal is to have a vaccine identified, tested and available on a scale of hundreds of millions of doses in just 12 to 18 months.

Drug companies and the governments and investors that finance them are boosting their “at-risk” spending in unprecedented ways. The overriding consensus among more than 30 drug company executives, government health officials and pandemic-response experts interviewed by Reuters is that the risks are necessary to ensure not only that a vaccine for the new coronavirus is developed quickly, but that it is ready to distribute as soon as it’s approved.

Investments from governments, global health groups and philanthropies have been aimed primarily at the most promising of the more than 100 vaccine candidates in development worldwide. But only a handful of those have advanced to human trials, the real indicator of safety and efficacy - and the stage where most vaccines wash out. Even among the more encouraging prospects, very few are likely to succeed. It’s possible more than one will work; it’s possible none will.

For companies in the race, there are some likely benefits: It’s a proving ground for vaccine technologies and a chance to burnish reputations and boost shares. While some large companies, including Johnson & Johnson and GlaxoSmithKline Plc , have said they plan to make the

vaccine available at cost - at least at first - they may reap profits down the road if seasonal vaccination is needed and countries invest in stockpiles.

But finding a vaccine that works does little good without the ability to produce and distribute it. That means building manufacturing plants now. “We want to make investments up front, at risk, even before we know the vaccines work, to be able to (immediately) manufacture them at a scale of tens or hundreds of millions of doses,” said Richard Hatchett, a physician who managed U.S. pandemic flu policy under former President George W. Bush and returned to advise the Obama White House during the 2009 swine flu pandemic.

Hatchett now heads the Coalition for Epidemic Preparedness Innovations (CEPI), a vaccine-development consortium supported by private donors as well as the United Kingdom, Canada, Belgium, Norway, Switzerland, Germany and the Netherlands. The organization has raised more than $915 million of the $2 billion it anticipates spending to accelerate testing and build specialized production plants for at least three coronavirus vaccine candidates.

In the United States, the Biomedical Advanced Research and Development Authority (BARDA), a federal agency that funds disease-fighting technology, has announced investments of nearly $1 billion to support coronavirus vaccine development and the scale-up of manufacturing for promising candidates. One underlying fear, shared by everyone Reuters interviewed, is that even if a vaccine does prove effective, there won’t be enough to go around.

Having reserves ready worldwide to immediately inoculate critical populations - health care workers, the elderly, people made vulnerable by medical conditions would stamp out the pandemic faster and reignite economies, Hatchett said. The alternative, he said, is a replay of past pandemics, including the H1N1 influenza outbreak of 2009, with wealthy countries hoarding the vaccines.

If that happens, pandemic experts warn, infection hot spots will continue to pop up, each with the potential to create a new wave of illness.

Full speed ahead

The scale of the coronavirus vaccine race has no historical parallels. CEPI has identified at least 115 ongoing vaccine initiatives worldwide. And the race is shattering norms of speed and safety in drug and vaccine development. Some developers are running safety and efficacy trials in tandem, instead of sequentially, as is typical, and short-cutting traditional testing protocols. Others are working with regulators in multiple countries simultaneously, looking for the quickest path to market.

The resulting uncertainty makes it especially risky to invest in manufacturing facilities for a given candidate, since different types of vaccines can require very distinct production lines.

Many of the candidates attracting the most investment rely on proven vaccine approaches being adapted by Big Pharma companies with regulatory and production acumen. Some funders are gambling on smaller biotech companies and academic labs, which may have promising technologies but little to no experience getting a drug or vaccine approved and produced at scale.

BARDA, the US R&D agency, is one of the biggest vaccine funders, with some $5 billion to spend. The agency plans to invest in five vaccine candidates, focusing mostly on projects from experienced drug makers. “Each is coming with a lot of prior experience,” said Rick Bright, who until this month was BARDA’s director. “They all know how to scale up.”

In one of its biggest bets, BARDA is pouring nearly $500 million into a J&J effort.

J&J’s coronavirus vaccine candidate uses a cold virus, rendered harmless, to deliver genes derived from the spiky, crown-shaped proteins on the surface of the new coronavirus, prompting an immune response.

J&J is using the same technology to develop vaccines for other viruses, including Ebola. While none has completed testing and won full US approval, trials so far in tens of thousands of people have produced data showing the basic approach is safe, which could speed regulatory approval for the new coronavirus vaccine. But it’s far from a sure bet: Animal test data, due this summer, will give the first hint of the vaccine’s effectiveness and human trials will begin in September.

“By end of the year, we’ll know whether it protects humans,” said Stoffels, J&J’s chief science officer.

In China, CanSino Biologics Inc has vaccine technology similar to the one being used by J&J. CanSino is further along with its testing, having announced this month that its candidate had cleared initial safety trials in humans and was set to advance to the next stage.

Sanofi SA, the world’s largest vaccine maker, has attracted BARDA money for another proven approach, based on its approved Flublok flu shot. Sanofi uses insect cells instead of the traditional chicken eggs to grow the genetically altered virus proteins used to spur an immune response.

Not all the vaccine projects getting attention have a Big Pharma pedigree.

Moderna Inc, a biotech firm based in Cambridge, Massachusetts, was the first in the United States to begin human trials when it began testing its vaccine last month. Working with the U.S. National Institutes of Health, the company received seed money from CEPI, and this month, BARDA kicked in $483 million to support the vaccine’s development and help scale up manufacturing. That includes hiring 150 skilled workers to eventually produce vaccine around the clock.

Moderna’s vaccine uses genetic material called messenger RNA (mRNA) to instruct cells in the body to make specific coronavirus proteins that then produce an immune response.

No mRNA vaccine has ever been approved for public use, but the technology is drawing interest, in part because it makes a vaccine easier to design and produce in vast quantities.

“The end game is millions of doses,” Tal Zaks, Moderna’s chief medical officer, told Reuters. The company hopes to have an approved vaccine available as early as March 2021, and possibly before then for healthcare workers. German vaccine makers CureVac and BioNTech SE , which is partnering with Pfizer Inc, are preparing to begin trials with similar mRNA-based vaccine candidates. So is Lexington, Massachusetts-based Translate Bio Inc, which is working with Sanofi.

Extraordinary shortcuts

Even for vaccine hopefuls already in human tests, it will be months before there’s conclusive evidence on safety and effectiveness - something funders are keenly aware of.

The rush has prompted scientists to consider previously unthinkable shortcuts.

Normally, vaccines would need to undergo clinical trials involving thousands of people before widespread inoculation is allowed. But after testing a prospective vaccine in a smaller group to ensure it is not toxic, Swiss researchers seek to “immunize a lot of the Swiss population in the next six months and then produce for a world market,” Dr Martin Bachmann, head of immunology at Inselspital, the University Hospital of Bern, said this week. A spokesman for Swissmedic, the country’s drug regulator, said it was in contact with Bachmann’s group and would not allow trials until the agency is assured that safety risks are addressed.

The Swiss vaccine employs virus-like particles to provoke an immune response, an approach that theoretically is considered safer because it does not directly expose people to the actual coronavirus. So far, it has only been tested in mice. Dr. Gregory Poland, a vaccine researcher at the Mayo Clinic in Rochester, Minnesota, is among those worried about the risks of injecting a large group of people with a vaccine that has only been through minimal testing in humans.

“I don’t see how this is possible,” he told Reuters, referring to Inselspital’s plan.

The war on COVID-19 is haunted by lessons from the fight against another virus a decade ago. In the spring of 2009, the H1N1 swine flu virus emerged in the United States and Mexico and spread worldwide. Within weeks, the World Health Organization(WHO) declared it the first pandemic since 1968.

Wealthier governments that had provisional contracts with vaccine makers immediately exercised them, “effectively monopolizing the global vaccine supply,” according to Hatchett and numerous official reports. The US alone ordered 250 million doses, and Australia, Brazil, France, Italy, New Zealand, Norway, Switzerland and Britain all had vaccine.

Under pressure from the WHO, those countries ultimately committed to share 10% of their stockpiles with poorer nations. But due to production and distribution snarls, only about 77 million doses were shipped - far less than needed - and only after the disease had peaked in many regions.— Reuters