US vaccine program now flush with cash, but brief on important details

Attempts to develop the next generation of Covid vaccines are facing bureaucratic hassles and regulatory uncertainty, scientists say, obstacles that could make it more difficult to contain the spread of the coronavirus and arm the United States against future pandemics.

The Biden administration has now at least addressed a shortfall in funding after months of delays and is rushing to provide the first major grants from a $5 billion program to accelerate a new class of more potent and sustainable inoculations .

But the program faces the blunt reality that vaccine development, after kicking into high gear early in the pandemic, has returned to its slower and more usual pace.

Experiments on a promising nasal vaccine licensed from Yale University have been delayed as researchers spent nearly a year trying to obtain older injections from Pfizer-BioNTech and Moderna for use in the studies. The federal government’s original purchase agreements for those injections prevent doses from being used for research purposes without the companies’ approval, despite the fact that tens of millions of unused injections have been wasted in recent months.

In Pennsylvania, a company developing an inhaled vaccine related to one already in widespread use in India said it unsuccessfully sought clarification on whether it qualified for funding from the US government. The vaccine, the company said, may not have been tested advanced enough to qualify for the new pot of US funding.

And in academic labs and start-up agencies across the country, vaccine makers are groping in the dark about whether clinical trials funded by the Biden administration will be large and sophisticated enough to convince regulators who are still figuring out what to do. need for clearance.

Federal officials, some of whom are concerned about the leadership of the next-generation vaccine program, acknowledged that important questions remain about how the program will work and how quickly it can be delivered. While some officials in the Biden administration hope to roll out new vaccine technology by fall 2024, many scientists believe the doses are at least several years away.

“There’s no money, there’s no infrastructure, there’s no support,” said John Moore, a virologist at Weill Cornell Medicine, of the push for improved vaccines. “So I don’t expect big things from the next generation in the near future.”

Pfizer and Moderna vaccines are powerful preventers of serious disease. But they’ve failed to stop variants like Omicron, which have left more Americans than usual out of work and some sickened by long-term covid. And they have failed to extinguish the danger to some vaccinated Americans, especially older people, adding to the weekly national Covid death toll in the hundreds.

While vaccine technology will dominate the US market as of 2020, major countries such as India and China have rolled out newer inoculations. If those vaccines perform better, they could fortify the United States against deadly future waves, just as a second generation of polio injections helped eliminate that disease from the country decades ago.

But newer Covid vaccines, which rely on less certain technology, are not a certainty. Some are sprayed into the nose or mouth to boost the immune system where the virus first enters, potentially preventing people from becoming infected. Others are designed to protect not only against variants of this virus, but also against other types of coronaviruses, making them a critical tool in a future pandemic.

With large pharmaceutical companies mostly on the sidelines and private investors wary of the market for next-generation vaccines, small biotechnology companies are struggling to advance inoculations due to the laborious and expensive clinical testing process.

“Covid is still here, and the scientific part of me thinks this is important and we should do it,” said Biao He, the CEO of CyanVac, referring to the company’s nasal Covid vaccine, one of the few who has completed enough advanced testing to qualify for extensive government funding. But when he met with investors about his company’s various products, he said, “The capitalist part of me says, ‘Maybe we shouldn’t talk about it.'”

Given the difficulties, vaccine makers have rushed to line up for the new federal money: More than 70 companies responded to the government’s recent call for candidates to apply, a spokesman for the Ministry of Health and Human Resources said services.

Federal health officials aim to finalize a handful of vaccine-related awards this summer and a dozen or more by early 2024, an official said.

But the key features of the initiative known as Project NextGen, including who will lead it, have led to divisions within the administration.

White House officials, hoping for a leader in the form of the former pharmaceutical director who oversaw a program in 2020 to accelerate vaccine development, vetted candidates from outside the administration and identified three finalists: Dr. Larry Corey, an immunologist at the Fred Hutchinson Cancer Center; Dr. Michelle McMurry-Heath, the former CEO of the Biotechnology Innovation Organization; and dr. David A. Kessler, the former chief science officer for the Biden administration’s Covid response, according to people familiar with the search.

But the health department has resisted an outside hire. “HHS is the one to execute and deliver,” said Xavier Becerra, the agency’s director, said this month at a Politico event. Some senior federal officials are concerned about whether the agency can operate with enough urgency, two federal officials said.

Dawn O’Connell, the health department’s assistant secretary for preparedness and response, defended plans to run the program internally through a health agency known as the Biomedical Advanced Research and Development Authority, or BARDA. “Within BARDA, we have the expertise to take these products to the finish line,” she said.

Scientists and health officials acknowledge that Project NextGen will struggle to measure up to its 2020 predecessor, Operation Warp Speed. That $18 billion federal effort, which came amid an onslaught of Covid deaths, accelerated vaccine development by helping companies test and produce injections at the same time. It also removed regulatory hurdles and ensured that the government bought the resulting vaccines.

Project NextGen, coined with Covid deaths at its lowest level, has nor the huge money of Warp Speed nor the mandate to buy shots in bulk.

Still, some experts have questioned whether the new initiative draws valuable lessons from Warp Speed.

Dr. For example, Corey noted that the 2020 program gave budding vaccine makers access to a publicly funded network of academic medical centers experienced in HIV vaccine testing, which helped recruit a more diverse group of tens of thousands of volunteers.

But that expertise won’t be available for next-generation inoculations. Instead, vaccine makers will have to pay private companies to conduct their trials.

“The devil is in the details,” said Dr. Corey, who leads the clinical trials network. “To make it happen, the HIV infrastructure we created and used in Warp Speed, and the studies I planned and conducted, need to be brought back into the system.”

Last month, the Biden administration asked vaccine makers to propose 10,000-person trials that would compare new inoculations to currently available booster injections. If the new vaccines are effective, they could attract the private funding needed for additional testing and production.

With strong results from that type of study, “the calculus is changing for you and your program,” said Marty Moore, chief science officer for Meissa Vaccines, whose nasal spray is a likely candidate for federal funding.

Still, it’s not clear how these proposed trials align with what the Food and Drug Administration might require to approve new vaccines.

The agency relied on larger investigations to clear the first coronavirus recordings in 2020. In early conversations about NextGen with the Biden administration, regulators suggested they might look for a similar level of data from the newer vaccines, two federal health officials said. But the details of their position are still being worked out, and regulatory agencies are considering approaching candidates in the program on a case-by-case basis, a health official said.

Regulators plan to publish guidelines for their standards in the coming months, officials said. “The agency is committed to remaining flexible in its approach to the data,” said Michael Felberbaum, an FDA spokesperson.

Regulatory uncertainty has hindered next-generation vaccine development for years, says Neil King, a biochemist at the University of Washington. To protect against new variants, or even other coronaviruses, his team has updated its previous Covid vaccine, which has been approved in South Korea and Britain.

But despite repeatedly asking the government for advice, he said, he has not received answers about what US regulators will look for in advanced studies of the new vaccine.

“Everyone is screaming for clarity,” he said.

The difference between smaller or larger studies could be hundreds of millions of dollars, said Dr. Bruce Turner, CEO of Xanadu Bio, which is developing Yale’s nasal vaccine.

“For a small business,” he said, “it’s really life and death.”

Most of the NextGen funding is only available to researchers whose vaccines have data from phase 1 trials and are ready for advanced studies within six months — a hurdle many groups have failed to overcome. The program will also fund early stage studies at the National Institutes of Health to compare lesser-tested vaccines and figure out how to measure immune responses, said Dr. John Beigel, an associate director for clinical research at the NIH.

But companies with early-stage vaccines expressed confusion about eligibility.

“A lot of companies don’t even qualify,” said Shankar Musunuri, the CEO of Ocugen, the Pennsylvania company with the inhaled vaccine. “They could have handled this in a more structured way.”

Bureaucratic issues have tripped up vaccine developers like Xanadu Bio, who can’t use Pfizer or Moderna vaccines for their experiments. The restriction stems from a provision in federal purchase agreements that is generally designed to protect companies from the risk of a poorly executed experiment harming their product, though it can also help protect companies from unflattering results.

Health officials said companies could get those doses as soon as the injections become available on the commercial market, a change not expected until late summer or fall.