After Moderna and Pfizer’s stellar results, the comeback players at Novavax face big questions about their best-in-class hunt in a frenzied Covid-19 vaccine race

On Nov. 9, Novavax R&D chief Gregory Glenn was awakened on his family farm to a news alert: Pfizer and BioNTech’s vaccine was more than 90% effective at preventing Covid-19.

It was incredible news for the world, and Glenn texted congratulations to old friends on the Pfizer-BioNTech team. But he also knew that it was complicated news for Novavax.

“I was not surprised that it worked, but to have 90, 95% efficacy? That’s really great,” Glenn told Endpoints News. “Admittedly, it puts a little additional pressure on me in other areas.”

Novavax, a tiny 33-year-old biotech that was teetering on insolvency before the coronavirus broke out, had emerged as one of the pandemic’s unlikeliest winners. Backed with $2.2 billion in new capital, including $1.6 billion from Operation Warp Speed, they were preparing for their own Phase III trials and laying the groundwork to produce up to 2 billion doses of the year.

The company’s protein-based technology was older and less flashy than the mRNA Pfizer and Moderna used, and it had failed before, in one notoriously difficult disease. But protein-based vaccines were known to be particularity immunogenic and over the summer, Novavax’s Phase I data appeared to show that their vaccine produced more neutralizing antibodies than its rivals.

That raised the prospect that mRNA would be first but Novavax might be best. Shares peaked at $178, a nearly 4000% increase from the $4.44 share price on Jan. 3.

“Before this result, everyone was thinking, well Novavax should have the best data,” Glenn said. “And mRNAs could be intermediate and vectors might be a little behind that.”

The Pfizer-BioNTech and Moderna results, though, all but eliminated that possibility before Novavax could even start a pivotal trial. It’s hard to improve on 95%.

Because all the major vaccine developers target the same coronavirus S protein, the Pfizer-BioNTech news gave Glenn more confidence in a candidate than he’s had in three decades designing and developing vaccines. Yet it also dramatically changed Novavax’s position in the race. Instead of gunning to be the best vaccine, at least in the short-term they will have to settle to be one of several good ones trying to supply the world, while also dealing with the all but inevitable delays that come from a small biotech trying to become a large one overnight.

Glenn, a self-described “gristled vaccinologist” who founded his first biotech more than two decades ago and has led the company’s R&D since 2010, is in charge of guiding the candidate through.

Bryce Chackerian

“I thought that if anything, their vaccine could be as good or perhaps even better — of course, when you’re at 95%, it’s gonna be hard to beat that,” Bryce Chackerian, a vaccinologist at the University of New Mexico, told Endpoints. Still,”any effective vaccine is going have a place in the marketplace, because it’s going to be a while before there’s enough.”

Novavax was hit with another setback Monday, when they announced that the launch of the Phase III US trial would be delayed for a second time, potentially pushing it into 2021.  The Gaithersburg, MD-based company has struggled in late stages in the past, raising hopes among investors and public health hopes around an RSV candidate that ultimately failed a 2016 trial.

The delay also raised questions about precisely how Novavax could run a Phase III study. Was it ethical to run a placebo-controlled study now that two vaccines appear to be highly effective? If it were, would people sign up? Memorial Sloan Kettering’s Peter Bach argued that at this stage, the comparator arm should be Pfizer or Moderna’s vaccine.

Glenn said the company was just working to get FDA clearance for commercial-scale manufacturing. They’ve spent a year trying to come from behind in that department, after they sold their production facilities to Catalent last year to keep the company alive. He said the current delays were minimal.

“No one would even know,” he said, if it weren’t for the Covid microscope. “It’s a normal process to scale up, create assays, create packaging around that.”

He said the Phase III US trial would be placebo-controlled as vaccines are still in short supply, but he acknowledged that the study might never be completed.

The company is also running trials in South Africa and the UK, where they’ve now completed enrollment. Depending on the timing, he said, the FDA might accept efficacy data from those studies, with some immunogenicity and safety data from the US trials, offering a path to approval even after vaccines have become broadly available in the country.

Data from the ex-US studies may come sooner than expected. Because of Pfizer and Moderna’s data, Novavax shortened the UK and South Africa studies, Glenn said. They now expect their own vaccine to be highly effective and that therefore they will need fewer cases to get a statistically significant result.

And although those results leave little room for Novavax to show better results against symptomatic disease, Glenn thinks there’s a chance their candidate may still be able to last longer or provide better protection from infection.

Chackerian said both ideas make sense: The more neutralizing antibodies you develop immediately after being vaccinated, for example, the more you’ll likely have a year later. Still, those questions remain speculative and he said he was more concerned about the apparent manufacturing issue.

While mRNA has storage requirements that can make it difficult to deliver globally, the world is already well-equipped to move protein vaccines. Any delay could mean delays in delivering badly-needed doses.

“Whether that represents a momentary glitch or points to more fundamental issues in scaling up production, I don’t know the answer,” he said. “But it’s certainly something that’s worth watching.”

A spokesperson for Novavax did not directly respond to a question about whether the manufacturing delays would change the amount of vaccine it can produce next year, saying only that once production is fully online, they should be able to produce 2 billion doses annually.

Glenn now spends his days in back-to-back meetings trying to get the clinical and manufacturing days running. He has helped develop candidates for RSV, E. Coli, Ebola, and pandemic flu since he founded his first biotech, IOMAI, in 1997. He most recently helped Novavax deliver positive Phase III results for a seasonal flu vaccine.

None of it, though, has been like this, and not just because of the scale of the crisis. Once the Pfizer and Moderna data came in, he said, he was certain they could do the same.

“The likelihood of success here is so high,” he said. “It feels like climbing the mountain, and it’s hard to wait.”

For a look at all Endpoints News coronavirus stories, check out our special news channel.

Click to view original post