By Sarah Jane Tribble and Rachana Pradhan
KAISER HEALTH NEWS (July 19) — On a sweltering June morning, Novavax CEO and covid vaccine maker Stanley Erck stood on a stage unmasked and did something that would have been unthinkable six months ago: He shook hands with Maryland’s governor.
Erck was with Gov. Larry Hogan to announce Novavax’s global vaccine headquarters ― a campus expected to house laboratories and more than 800 employees. Hogan called Novavax’s future “bright” and marveled that more than 71% of the state’s adults had received at least one shot.
None of those was a Novavax vaccine, which is still unavailable for the American public due to delayed clinical trial results and other difficulties. Hogan, for his part, received his first vaccine dose ― made by fellow biotech upstart Moderna ― in January.
“As you can imagine, we’re eager to receive our own,” said John Trizzino, Novavax’s chief commercial officer and interim chief financial officer. Its two-dose covid vaccine, which showed overall 90.4% efficacy in key U.S. and Mexico trials, has yet to be authorized. “In the meantime,” Trizzino said, “we’ve had to use one of the existing licensed vaccines and we look forward to the booster” made by Novavax.
Looking forward has kept Novavax afloat for decades ― along with its deep ties to grant makers and federal agencies. With its focus on developing vaccines, including for the SARS and MERS pandemics, Erck argues Novavax is “built for this moment.” Still, the 34-year-old startup has never brought one to market.
Novavax’s quest to scale up operations underscores how difficult it can be to launch a vaccine ― even with the formula and technology in hand. So what happened? It has had the financial backing of the U.S. government and full faith of international agencies. Everything took longer than expected: hiring necessary researchers and scientists, getting supplies and transferring its vaccine technology. It didn’t move at warp speed.
America is awash with vaccine options, and Novavax does not plan to file for regulatory authorizations until late July at the earliest. The delay could have dire consequences for people across the globe awaiting a vaccine.
“We’re not making aspirin,” Trizzino said. “We’re making a very complicated biological.”
A year before the covid pandemic hit, Novavax had a failed late-stage trial on a potential respiratory virus vaccine, after which it cut its workforce and sold off all its manufacturing capabilities. So, when more than $2 billion in federal and international funding landed at its doorstep, Novavax found itself developing both “a vaccine and a company” in 12 months, said Dr. Gregory Glenn, president of research and development.
Novavax’s proprietary secret ingredient is Matrix-M, an immune booster. Executives say the additive ― derived from Chilean soapbark trees ― works so well that less of an antibody-producing antigen would be needed with it in a vaccine. One financial filing said Matrix-M “has the potential to be of immense value.”
Equipped with its recombinant nanoparticle vaccine mixed with Matrix-M, Novavax deployed a core team of employees, dubbed “SuperNOVAs,” to crisscross the globe. They assembled a manufacturing network and shared vaccine technology in India, South Korea, Spain, Japan and the Czech Republic as well as in the United States ― about 20 contract manufacturing and test sites in all.
“This takes time and expertise,” Trizzino said. “You just simply can’t hand over the recipe and then walk away from it and expect you’re going to have a high-quality product.”
Novavax is contracted to form the backbone of the COVAX initiative, having promised 1.1 billion doses starting this year for developing countries. And while President Joe Biden announced the U.S. would donate 500 million doses of the Pfizer-BioNTech vaccine abroad, Novavax is still seen as vital to urgent efforts worldwide to battle the virus and its variants.
Novavax’s moonshot goal of producing 2 billion shots a year increasingly looks like a pipe dream for 2021. “It is very hard to accept that they will make 2 billion doses as they had originally committed. I’m very skeptical,” said Prashant Yadav, a health care supply chain expert and senior fellow at Harvard’s Center for Global Development.
One of Novavax’s biggest challenges, Yadav said, is relying on “so many sites” that aren’t fully under its control, while other manufacturers own their plants. The more places Novavax produces the vaccine, the more challenging it is to make sure the vaccine and its elements are comparable in every place.
When Novavax executives announced another delay in May, the company’s stock plummeted to $121 a share ― down 62% from a high of about $319 in February. As the company’s fortunes rose last year, Novavax executives cashed out tens of millions of dollars in common stock, according to securities filings. Last year, after the company benefited from grants and government contracts, CEO Erck sold $9.3 million in company shares, Glenn sold $14 million, and Trizzino sold $11.3 million.
Those top executives continued selling in 2021. Erck sold more than $22.5 million worth of common stock in early July.
Novavax executives use trading plans, and the sales often appear at the same time each month. In June, after Novavax announced its long-awaited U.S. and Mexico clinical trial results, Glenn sold more than 8,000 shares for $1.5 million. As a measure of the company’s spectacular rise in the pandemic, Glenn purchased 1,000 shares of stock in December 2016 for the price tag of just $1,446.
Novavax spokesperson Amy Speak said the company has programs in place to ensure best practices on stock sales. “Most people, including our executives, sell stock for a wide variety of reasons,” she said, adding that Novavax’s executives have “generally sold a fraction of their overall holdings in the company.”
Charles Duncan, a biotechnology research analyst at Cantor Fitzgerald, called Novavax a “show me” investment in May. “It’s one thing to have a place to make it,” he said. “It’s another thing to be able to make it there and get it certified.”
John Kutney, Novavax’s senior director of manufacturing, joined a BioBuzz video in December, in an effort to recruit urgently needed talent. Kutney described the technology transfer as taking a recipe and teaching it to others. With that mission, he has traveled to the Czech Republic, Spain and the United Kingdom as well as Texas, North Carolina and New England.
When Novavax began work on its vaccine in January 2020, “most of us hadn’t heard of covid-19 and we were only beginning to become aware of what was happening in China,” Kutney said. Novavax adapted its established vaccine platform to the new virus and then had to scale and transfer it to larger manufacturing sites, build a global supply chain and develop a regulatory strategy for emergency use.
“These steps would normally take years,” he said.
The key step of transferring Novavax’s vaccine technology can take three to six months, depending on the quality of the partner’s team. Once equipment and raw materials are secured, the teams start with small batches ― first with a 50-liter bioreactor, then a 200-liter and eventually a 2,000-liter bioreactor, checking to make sure the partner operators know the process every step of the way.
“What we’re trying to do here is not easy,” said Fred Shemer, Novavax’s vice president of quality systems and compliance, in the video: “It’s a challenging situation.”
In March 2020, Novavax received the first $4 million of nearly $400 million pledged by the Coalition for Epidemic Preparedness Innovations. CEPI is a global alliance backed by the Bill and Melinda Gates Foundation, which previously supported Novavax with $89 million for a vaccine for a common respiratory virus.
CEPI’s investment jump-started Novavax’s technology transfer to plants across Europe and Asia. It helped Novavax partner with SK bioscience in South Korea and paid for ramping up production at Praha Vaccines, which Novavax eventually bought, in the Czech Republic. It also supported scaling up production of Matrix-M at facilities in Sweden and Denmark.
Operation Warp Speed awarded $1.6 billion in July 2020 to Novavax so it would produce 100 million doses ― one of the largest awards from the Trump administration’s vaccine incubator. It was “kind of a stunning number for us,” Trizzino said. In December, officials bumped the total to $1.74 billion with no changes to the previous contract. Novavax also has a $60 million contract with the Department of Defense for 10 million doses.
Paul Mango, a former senior official at the Department of Health and Human Services, said it wasn’t a “big concern” for the Trump administration that Novavax had no successful vaccine. After all, that was also true for Moderna, which went on to launch its wildly successful mRNA vaccine.
Operation Warp Speed’s personnel resources and financial support would help carry the day. “We thought we could do it,” Mango said.
At the time, Trump officials invested in several vaccine platforms to hedge bets because it wasn’t known what would work, if any. “We didn’t want to put all our eggs in mRNA,” he said. “We didn’t want to put all our eggs in viral vector,” the platform used by Johnson & Johnson and AstraZeneca. Novavax’s technology uses a more established process with a baculovirus grown inside insect cells in a bioreactor.
“It was very important to have that array of technologies,” Mango said. “We had to pick the ones that had the best early results and the ones we thought could go through clinical trials before the spring of 2021.”
Novavax scientists have spent years collaborating with officials at federal agencies such as the National Institutes of Health, National Institute of Standards and Technology, and Walter Reed National Military Center ― sometimes hiring from their ranks. In 2011, Novavax signed a $179 million contract to develop a seasonal and pandemic influenza vaccine with BARDA, the Biomedical Advanced Research and Development Authority.
As concerns about covid-19 rose, Novavax and BARDA began another negotiation, but Operation Warp Speed officials “stepped over the top,” Trizzino said. They asked Novavax what it would take to ramp up large-scale manufacturing, run a 30,000-subject clinical trial and the follow-on trials, and produce millions of doses.
“They said, ‘Do all these things in parallel paths. You don't worry about the funding risk. You do the work and we'll pay for those activities,’” Trizzino recalled.
It was a tall order. Novavax had worked with Emergent BioSolutions and signed a contract for manufacturing in early 2020, but BARDA pushed Novavax to partner instead with Fujifilm Diosynth Biotechnologies and its plants in North Carolina, Texas and the U.K.
In retrospect, Trizzino said, Novavax “dodged a bullet.” Production problems at Emergent’s Baltimore plant led to contamination or suspected contamination of millions of Johnson & Johnson and AstraZeneca doses, and in June federal regulators declared 60 million J&J doses unusable, The New York Times first reported.
Fujifilm’s Texas site, like Emergent’s plant in Baltimore, was set up in the aftermath of the 2009 H1N1 pandemic to better prepare federal officials for the next one. It received $265 million last July to quickly boost manufacturing capacity, according to a federal contract.
The site began production in January but had to slow the cadence of its manufacturing lines for “troubleshooting” during Novavax’s technology transfer process, Fujifilm spokesperson Christine Jackman said. The plant is producing the Novavax vaccine and another undisclosed covid vaccine.
Trizzino said Fujifilm’s site in North Carolina was up and running quickly, but Texas didn’t have as much experience so “it’s taken us a bit longer to ramp that up.” A March inspection by the Food and Drug Administration found overcrowded and unorganized storage areas, a failure to consistently follow cleaning procedures and questions about why there was a backlog of batches, according to documents obtained by KHN in response to a public records request. The backup formed because bulk drug substance was being made faster than the facility could review produced batches, Fujifilm’s Jackman said.
FDA inspectors called Fujifilm’s operations “sub optimal quality,” according to an April response memo written by Gerry Farrell, Fujifilm’s chief operating officer for the facility. He said the criticism resonated and promised a thorough review with fixes completed in April and May.
Novavax and Fujifilm work closely to ensure all batches are reviewed and inspected by both companies’ quality control teams, said Speak, the Novavax spokesperson. The number of doses produced in Texas to date have not met projections. However, responding to federal inspections in Texas has not delayed Novavax’s vaccine development because Fujifilm’s North Carolina plant is the primary supplier of vaccine doses for the initial federal approval, Speak said.
Novavax’s manufacturing process is complicated because the vaccine is made in steps in different places. One plant makes the protein antigen, and another makes the adjuvant. Then the two components go to a final fill-and-finish facility where they are combined into 10-dose vials.
Its Matrix-M relies on quillaja extract from soapbark trees. The extract is also an additive in root beer and Slurpees. Novavax warned investors in its December 2020 financial filings that an inability to secure enough of the extract could delay production and prevent it from meeting “obligations under our various collaborations and supply agreements.” Still, Trizzino said that supply is “not an obstacle to total number of doses.”
Supply shortages have plagued the industry. For Novavax, those supplies included 2,000-liter bioreactor bags, used to culture cells; depth filters for the purification process; and the growth media, which is used to feed the cells.
Not having raw materials forced Novavax to trim the number of test batches that manufacturing lines could run. It has also taken longer to create quality control tests, known as assays, to ensure that vaccines are consistent and establish a standard quality for all subsequent batches. Those delays slowed the company’s ability to properly train operators, Trizzino said.
Novavax is working to reach “a level of comfort that we're able to produce these batches and then go to full capacity,” Trizzino said. Novavax is working to complete the final phases of validating those tests.
At the headquarters event, Glenn acknowledged that Novavax is late to the game. But the global demand is still enormous, he stressed.
“We know that 2 billion people worldwide have received at least one shot,” he said, “but there are 6 billion people that need to be inoculated.”
The company is working to prove its vaccine will be useful even after the pandemic is contained. With its Matrix-M adjuvant, Novavax is testing a combined flu and covid vaccine, which is showing strong results in ferrets and hamsters. Novavax is also focused on booster shots.
Novavax joined mix-and-match trials this spring in the U.K. to test whether its vaccine works when paired with Moderna, Pfizer or AstraZeneca’s vaccines. Glenn said the results, so far, have been promising that “we’re going to be able to use our vaccine after other licensed vaccines.”
First, though, “the world has to collectively, as one, really stymie this global pandemic,” said Dr. Dawd Siraj, a University of Wisconsin professor specializing in infectious diseases.
Siraj said Novavax’s delays shouldn’t cast doubt on the quality of the vaccine itself, given the positive trial results it has reported globally.
The shot is a “very good vaccine,” he said, that could help turn the tide in developing countries unable to support their own vaccine development.
“Let us never miss the most important point here,” Siraj added. “Anyone who is getting a vaccine that is approved, the chances of dying, the chances of requiring ICU care, the chances of requiring a ventilator and high-flow oxygen, they almost disappear.”