May 10, 2021

Maker of latest experimental vaccine will not seek authorization until July at the earliest

The Novavax coronavirus shot, which relies on a more traditional technology, could be a key tool in the global effort to fight the pandemic

by Carolyn Y. Johnson
WashingtonPost.com

A 34-year-old Maryland biotechnology company that has never successfully launched a vaccine faces a world impatient for more coronavirus shots to quell a pandemic — but the wait isn’t over.

Novavax, bolstered by $1.6 billion in federal funding, is unlikely to seek emergency use authorization for its experimental coronavirus vaccine in the United States until July at the earliest, the company announced on its quarterly earnings call. The Washington Post reported early Monday that the filing was delayed by manufacturing regulatory issues, until June at the earliest, according to four people who had recently been briefed on the company’s plans.

“We know that we are delayed from where we thought we would be at this point,� chief executive Stanley Erck said in announcing the company expected to complete applications for authorization in the United States, the United Kingdom and Europe in the third quarter. “Now, we’re giving guidance that nearly all of the major challenges have been overcome and we can clearly see the light at the end of the tunnel.�

As supplies of three authorized coronavirus vaccines have increased in the United States, the role of the Novavax vaccine domestically remains unclear. But the company’s shots, shown to be about 90 percent effective in a 15,000-person United Kingdom trial, could fill an urgent global need — an easy-to-store vaccine that could help bolster strained supplies as the pandemic rages. However, that depends on the company earning regulatory clearance and scaling up manufacturing.

Novavax, which didn’t have its own manufacturing capacity at the beginning of the pandemic, has set an ambitious goal of producing 2 billion doses a year, relying on a global manufacturing network. But the company’s challenges have multiplied even as the urgency has increased.

Novavax’s 30,000-person North American trial of the vaccine has been delayed several times; originally planned to launch in October, it didn’t begin until the last days of December because of manufacturing delays. All the vaccine trials have moved forward at an uncertain pace as researchers wait to see which study participants develop covid-19, the illness caused by the coronavirus.

But Gregory Glenn, Novavax’s president of research and development, told a Washington Post Live audience in February that results from his company’s trial were expected “right at the beginning, maybe� of the second quarter, which started April 1.

Those trial results are now not expected until the end of May, according to four people who have been briefed on the status of the study and spoke on the condition of anonymity to speak freely. Erck told investors that the results would be shared “in a few weeks.�

The company then would not seek emergency use authorization in the United States until July at the earliest, Erck said. The delay is due in part to a regulatory manufacturing issue related to an assay, the people briefed on the trial status told The Post. Assays are tests used throughout the manufacturing process to check the contents and quality of vaccines.

“The filing timetable depends on completing the final phases of qualification and validation of the assays that are needed� to show regulators that the manufacturing process is consistent every time, Erck said.

If the U.S. regulatory review follows the same expedited path as for earlier coronavirus vaccines, that means authorization of the Novavax vaccine would not be likely until well into summer.

Novavax executives also disclosed that raw material shortages were delaying its ability to reach manufacturing targets. The company now expects to reach full capacity of producing 150 million doses a month by the final three months of the year. Erck predicted “a somewhat slower rollout on product approval, but not dramatically.�

Novavax’s vaccine has been highly anticipated by many experts because it would add a more traditional technology to the portfolio of coronavirus vaccines in the United States. Other vaccines work by instructing the body’s cells to build the spiky proteins that dot the outside of the coronavirus. The immune system learns from the exposure to recognize the real thing.

But Novavax’s vaccine consists of that spike protein, generated inside insect cells that grow in giant bioreactors. The approach is innovative, but protein-based vaccines have been used for decades, including one for hepatitis B.

Expectations are high because the vaccine is expected to be powerfully effective. The trial in the United Kingdom found the Novavax vaccine was nearly 90 percent effective. It was 60 percent effective among HIV-negative people in a trial in South Africa, where a variant capable of dodging some immunity was dominant. The company has set up a manufacturing network with partners in many countries to supply its vaccine, which can be stored at refrigeration temperatures.

But the vaccine has consistently lagged behind hoped-for timelines, raising questions from scientists.

About two weeks ago, the company began crossing over participants in the United States, giving doses of the real vaccine to those who initially received a placebo. John P. Moore, an immunologist at Weill Cornell Medicine who works on protein vaccines against HIV and volunteered for the North American trial, said he soon will receive his second shot, and he and others are eager to see the results.

“Everyone’s puzzled,� Moore said about why the Novavax results won’t come out sooner. He speculated that the small company, which has grown overnight to meet the challenge of getting a coronavirus vaccine to the world, may simply be struggling with the magnitude of the task. “It seems to be a company perhaps too small to cope with what’s on their desk.�

To stay financially afloat after earlier scientific setbacks, Novavax sold its manufacturing facilities in 2019. There were only about 150 employees left at the company at the beginning of 2020. Now, there are more than 800.

“That’s why we’re several months behind everyone, because we did not have a manufacturing facility. We had to build a company, we had to build a manufacturing network and develop a vaccine,� Glenn said in an interview. “Big challenges.�

Novavax has never launched an approved vaccine and is relying on partners in countries around the world to manufacture its doses, and it has dealt with manufacturing issues for the past year. Early batches of its coronavirus vaccine were made at Emergent BioSolutions in Baltimore, but that factory switched to focus on AstraZeneca and Johnson & Johnson. Novavax had to move production to Fujifilm Diosynth Biotechnologies in North Carolina.

In late October, Novavax announced in a news release it had made “significant progress in large-scale manufacturing, with delays experienced.� A month later, when the trial was delayed again, the company said it was “working closely with� the Food and Drug Administration on necessary steps before its product could be used in trials.

“It may seem like Novavax is taking a long time to get through their development, but the benchmarks have been set from vaccines that have moved very, very fast,� said Rajeev Venkayya, president of the Global Vaccine Business Unit at Takeda Pharmaceutical, which has partnered with Novavax and plans to manufacture 250 million doses a year in Japan. “When it comes to developing tests for biological materials, that can be very complicated and can lead to long timelines in vaccine development.�

Vaccines are complex biologic products manufactured by living cells, and each step of that process must be repeated with consistent results as it scales up. Getting that right, validating the steps and then replicating them perfectly each time is crucial and takes time.

“It’s not like making aspirin or a small molecule; this is very complex,� said Norman W. Baylor, a former FDA vaccine expert and president of Biologics Consulting. “That whole process of getting the cells to do what they need to do, making sure the expression is proper, all these steps — there are hundreds and thousands of steps involved in making a vaccine, especially with the new technologies, and each of these steps have to be validated.�

Novavax chief executive Erck said Monday that shortages of essential raw materials, including massive 2,000-liter bags used to grow cells and filters used in the purification process, have posed a difficulty.

Reuters reported that the company has faced raw material shortages and production problems in Europe and will begin sending a small number of doses to European countries at the end of the year, with most of 200 million shots to be delivered in 2022.

More than 1 billion doses of the Novavax vaccine have been pledged to the global initiative to distribute the vaccine to poor and middle-income countries. That campaign is backed by the World Health Organization, but it has struggled to secure enough vaccine doses. On Thursday, Novavax announced that 350 million of those doses would begin to be delivered starting in the third quarter of this year.

http://www.washingtonpost.com/health/2021/05/10/novavax-coronavirus-vaccine/