Special report: countries and companies at risk of billions in race for coronavirus vaccine

(Reuters) – In the race to develop a vaccine to end the COVID-19 pandemic, governments, charities and large pharmaceutical companies are investing billions of dollars in bets with extraordinarily low odds of success.

They are accelerating the testing and regulatory review of vaccines without guarantee that they will be effective. They are building and remodeling vaccine plants with little chance of being approved. They are ordering vaccines that, in the end, are unlikely to occur.

It is the new paradigm of the pandemic, focused on speed and full of risks.

“The crisis in the world is so great that each of us will have to take the maximum risk now to stop this disease,” said Paul Stoffels, chief scientific officer of Johnson & Johnson (JNJ.N), which has partnered with the United States government in an investment of $ 1 billion (£ 808.6 million) to accelerate the development and production of its unproven vaccine. “If it fails,” Stoffels told Reuters, “it will be bad.”

Historically, only 6% of vaccine candidates end up hitting the market, often after a years-long process that doesn’t generate big investments until tests show a product is likely to work. But traditional rules of drug and vaccine development are being pushed 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.

Pharmaceutical companies and the governments and investors that finance them are increasing their spending “at risk” in an unprecedented way. The general consensus among more than 30 pharmaceutical company executives, government health officials and pandemic response experts interviewed by Reuters is that the risks are necessary to ensure that not only is a vaccine for the new coronavirus rapidly developed, but that it is ready to be distributed as soon as approved.

Investments from governments, global health groups, and philanthropies have been directed primarily at the most promising of the more than 100 developing vaccine candidates worldwide. But only a handful of them have advanced to human trials, the true indicator of safety and efficacy, and the stage when most vaccines disappear.

Even among the most encouraging prospects, very few are likely to succeed. More than one may work; none may.

For companies on the run, there are some likely benefits: It’s a testing ground for vaccine technologies and an opportunity to buff reputation and boost stocks. While some large companies, including Johnson & Johnson and GlaxoSmithKline Plc (GSK.L), have said they plan to make the vaccine available at cost, at least initially, they may reap future profits if seasonal vaccination is needed and countries invest in stocks.

But finding a vaccine that works is useless 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 vaccines work, so we can make them (immediately) on a scale of tens or hundreds of millions of doses,” said Richard Hatchett, a physician who administered US policy. against pandemic influenza under former President George W. Bush and again advised the Obama White House during the 2009 swine flu pandemic.

Hatchett now heads the Coalition for Outbreak 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 Advanced Biomedical Research and Development Authority (BARDA), a federal agency that funds disease-fighting technology, has announced investments of nearly $ 1 billion to support the development of the coronavirus vaccine and the expansion of manufacturing for promising candidates.

An underlying fear, shared by everyone interviewed by Reuters, is that even if a vaccine is effective, there will not be enough for everyone.

Having stocks ready around the world to immediately inoculate critical populations (health workers, the elderly, people vulnerable to medical conditions) would end the pandemic faster and revive economies, Hatchett said. The alternative, he said, is a repeat of past pandemics, including the 2009 H1N1 influenza outbreak, with wealthy countries hogging the vaccines.

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

MAXIMUM SPEED FORWARD

The coronavirus vaccine breed scale has no historical parallels. CEPI has identified at least 115 ongoing vaccine initiatives worldwide. And the race is breaking speed and safety standards in drug and vaccine development.

Some developers are running safety and efficacy trials together, rather than sequentially, as is typical, and shorten traditional testing protocols. Others are working with regulators in several countries simultaneously, looking for the fastest path to market.

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

Many of the top-attracting candidates rely on proven vaccine approaches that are being tailored by large pharmaceutical companies with a regulatory and production vision. Some funders are betting on smaller biotech companies and academic laboratories, which may have promising technologies but little or no experience in obtaining an approved, scale-produced drug or vaccine.

BARDA, the US R&D agency. The US is one of the largest vaccine funders, with about $ 5 billion to spend. The agency plans to invest in five candidate vaccines, mainly focusing on projects from experienced drug makers.

“Each one comes with a lot of previous experience,” said Rick Bright, who until this month was BARDA’s director. “Everyone knows how to climb.”

In one of his biggest bets, BARDA is investing nearly $ 500 million in a J&J effort.

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

J&J is using the same technology to develop vaccines for other viruses, including Ebola. While none of them completed the tests and obtained full US approval. So far, trials in tens of thousands of people have produced data showing that the basic approach is safe, which could accelerate regulatory approval for the new coronavirus vaccine. But it is far from a safe bet: data from animal tests, to be conducted this summer, will give the first clue to the vaccine’s effectiveness, and human trials will begin in September.

“By the end of the year, we will know if it protects humans,” said Stoffels, chief scientific officer at J&J.

In China, CanSino Biologics Inc (6185.HK) has a similar vaccine technology to that used by J&J. CanSino is more advanced along with its tests, as it announced this month that its candidate had passed initial human safety tests and was ready to advance to the next stage.

Sanofi SASASY.PA), the world’s largest vaccine maker, has attracted money from BARDA for another proven approach, based on its approved Flublok flu vaccine. Sanofi uses insect cells instead of traditional chicken eggs to cultivate the genetically altered viral proteins that are used to stimulate an immune response.

Not all vaccine projects that receive care have a pedigree from Big Pharma.

Moderna Inc (MRNA.O), a biotechnology company 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 US National Institutes of Health. The company received seed capital from CEPI, and this month BARDA provided $ 483 million to support vaccine development and help increase manufacturing. That includes hiring 150 skilled workers to eventually produce vaccines 24 hours a day.

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

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

“The end game is millions of doses,” Tal Zaks, medical director of Moderna, told Reuters. The company hopes to have an approved vaccine available starting in March 2021, and possibly sooner for healthcare workers. German vaccine manufacturers CureVac and BioNTech SE (22UAy.F) (BNTX.O), which is associated with Pfizer Inc (PFE.N), are preparing to start trials with similar mRNA-based vaccines. This is Translate Bio Inc, based in Lexington, Massachusetts (TBIO.O), who is working with Sanofi.

EXTRAORDINARY SHORTS

Even for vaccine applicants already undergoing human testing, it will be months before there is conclusive evidence on safety and efficacy, something the funders are well aware of.

The rush has led scientists to consider shortcuts that were previously unthinkable.

Normally, vaccines would need to undergo clinical trials with thousands of people before widespread inoculation is allowed. But after testing a possible vaccine in a smaller group to make sure it’s not toxic, Swiss researchers are looking to “immunize a lot of the Swiss population in the next six months and then produce for a world market,” said Dr. Martin Bachmann. , chief 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 that it would not allow trials until the agency is sure that the security risks are addressed.

The Swiss vaccine uses virus-like particles to elicit an immune response, an approach that is theoretically considered safer because it does not directly expose people to the real coronavirus. Until now, it has only been tested on mice.

Dr. Gregory Poland, a vaccine researcher at the Mayo Clinic in Rochester, Minnesota, is among those concerned about the risks of injecting a vaccine into a large group of people who have only undergone minimal human testing.

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

Lessons not learned

The war against COVID-19 is haunted by the lessons of fighting 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. In a few weeks, the World Health Organization (WHO) declared it the first pandemic since 1968.

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

Under pressure from the WHO, those countries finally committed to sharing 10% of their stocks with the poorest nations. But due to the growls of production and distribution, only around 77 million doses were sent, far less than necessary, and only after the disease peaked in many regions.

If an effective vaccine for the new coronavirus emerges, a repeat is possible, experts say in pandemic preparedness. None of the global health authorities consulted by Reuters believe there will be sufficient supplies to meet immediate demand. Governments will be under tremendous pressure to immunize their own citizens and return to normal life, so hoarding remains a serious risk.

Ronald St. John, a physician who has held government positions in infectious disease control in the United States and Canada, expects a similar scenario with vaccines.

“There will be a lot of self-interest in terms of production,” he said.

BARDA explicitly gives preference to vaccine projects that promise production capacity in the United States.

“We are asking the American taxpayer to contribute a lot” to the vaccine effort, so it is important to guarantee US access. USA Any successful vaccination, said Bright, recent BARDA chief.

But he added that BARDA is also encouraging companies it supports to build manufacturing capacity outside the United States, “so that we can have a global supply at once.”

Many governments are pouring money into vaccine initiatives with the expectation that they will be first in line if a viable vaccine emerges.

Arcturus Therapeutics Holdings Inc (ARCT.O), a San Diego biotech, is receiving up to $ 10 million (8 million pounds) from the Singapore government to develop its candidate mRNA-based coronavirus vaccine in association with the Duke School of Medicine at Singapore National University. If the vaccine is approved, Singapore gets the first access, said Arcturus CEO Joseph Payne. Everything that follows, he said, goes to “whoever pays for it.”

“Arcturus is not responsible for the ethics of distribution, governments are, but for governments to receive the vaccine, they must pay for it,” Payne said. “The country that will win is the country that stores multiple vaccines at risk.”

The company raised $ 80.5 million this week from a public offering of common stock.

In China, one of the world’s leading vaccine producers, the government supports several coronavirus vaccine projects, increasing the chance that it will first inoculate its 1.4 billion people. A government-backed effort by Sinovac Biotech Ltd. (SVA.O), is already testing vaccine candidates in humans and waiting for initial data.

Sinovac obtained 60 million yuan ($ 8.4 million) in low-rate lines of credit through a discount loan program backed by China’s central bank. Government officials quickly made land available for the company to build production plants, including a factory set to produce up to 100 million doses a year of its coronavirus vaccine.

Sinovac did not discuss how much public money is being invested. Relevant government agencies rejected requests for comment.

On Friday, the World Health Organization announced a “landmark collaboration” across the international community to raise $ 8 billion to accelerate the development of the coronavirus vaccine and ensure equitable worldwide access to any vaccine. successful. Countries in Europe, Asia, Africa, the Middle East and America announced their participation, but the United States and China, two of the world’s largest pharmaceutical forces, did not.

“There will be no official United States involvement,” a spokesman for the US mission in Geneva told Reuters, adding that the United States supports “global cooperation to develop a vaccine.”

Broader questions about US policy USA International distribution of vaccines are still under consideration within the Trump administration, according to a member of the White House coronavirus task force who spoke to Reuters on condition of anonymity. The official noted that the United States Department of State and the United States Agency for International Development are spending nearly $ 500 million to help with the COVID-19 response internationally.

A WHO spokeswoman said Friday’s announcement was the start of a global collaboration and “we would welcome more countries to join.” China did not respond to a request for comment.

People involved in the global vaccine race told Reuters that the biggest incentive for countries to promise to share coronavirus vaccines may be uncertainty about which ones will work.

Since no country can be sure that the candidates it supports will be successful, committing to share with other nations can help ensure that they will have an initial supply to inoculate health workers and other critical populations.

“That is enlightened self-interest as well as a global public good,” said Jeremy Farrar, an infectious disease expert and director of the global health charity Wellcome Trust.