Remitido por Ruben Piacentini

By Meredith WadmanJun. 14, 2021 , NEWS from Sience

The dark horse vaccine company Novavax announced strong results today from a pivotal, 30,000-person trial of its pandemic coronavirus vaccine in the United States and Mexico. The vaccine uses a protein of SARS-CoV-2, a different technology from the COVID-19 vaccines authorized so far, and delivered 90.4% overall efficacy against symptomatic COVID-19 infections, and 100% protection against moderate and severe disease. Against eight viral variants of interest and concern, its efficacy was 93.2%. And the vaccine appeared safe and well-tolerated.

“This vaccine looks phenomenal. I am thrilled about these results,” says Monica Gandhi, an infectious disease physician and epidemiologist at the University of California, San Francisco. She notes that the clinical trial was highly diverse, with 44% nonwhite participants, and that the vaccine’s straightforward storage requirements could speed access to it in remote communities around the globe.

The difference of a few percentage points between Novavax’s 90% efficacy and the 95% and 94% efficacy of the Pfizer-BioNTech and Moderna vaccines is explained in part by Novavax’s later trial, which pitted the vaccine against viral variants, says John Moore, an immunologist at Weill Cornell Medicine and a participant in the Novavax trial. The trials of those other companies’ vaccines, composed of messenger RNA (mRNA), were completed before such variants were widely circulating.

“This is a vaccine whose efficacy is at least on a par with Pfizer and Moderna,” Moore says. “It’s essentially 100% protective against disease.”

One expert is less impressed, however. “The data they have [are] nothing spectacular,” says Vijay Samant, CEO of Xiconic Pharmaceuticals and former chief operating officer of Merck’s vaccine division. “The efficacy overall is couple of notches below the Pfizer and Moderna studies. … It’s a me-too vaccine at best.”

Novavax plans to apply to the U.S. Food and Drug Administration and other regulators for an emergency use authorization in the third quarter, once the company completes regulatory requirements aimed at ensuring its product consistently matches the vaccine used in the clinical trials, said President and CEO Stanley Erck.

Today’s announcement marks the end of a very long beginning for the once-moribund Gaithersburg, Maryland, company, which began to develop a vaccine in January 2020 and that July won $1.6 billion from the U.S. government’s Operation Warp Speed. But the company encountered production problems that delayed the launch of its North American clinical trial until late December 2020.  

In the trial, two-thirds of participants at 113 sites in the United States and six sites in Mexico initially received two doses of the vaccine separated by 21 days. One-third of participants received a placebo. Between 25 January and 30 April, participants experienced 77 cases of COVID-19, 63 of them in the placebo group. All 14 cases in vaccinated participants were mild.

These results are similar to those Novavax reported in January from a late-stage trial of more than 15,000 people in the United Kingdom. That trial showed the vaccine efficacy was 89% overall, 86% against the Alpha variant that was first identified in the United Kingdom, and 96% against the original virus strain. But in a separate trial involving 4400 participants in South Africa, where the worrisome Beta variant arose and was circulating widely, the vaccine’s overall efficacy sank to 49%.

In the new trial, Novavax sequenced 70% of all the coronaviruses that caused illness. In more than half of the sequenced cases, they found the culprit was the Alpha variant, which accounted for 70% of U.S. infections by late April. But the company did not provide specific efficacy data against Alpha or any other variant. (Only two cases of the Beta variant were reported in the trial.)

“It doesn’t really address the lingering questions about how well the vaccine would work against ‘escape’ variants” such as Beta, says Natalie Dean, a biostatistician at the University of Florida.

The COVID-19 vaccines so far authorized by major Western regulatory agencies deliver genetic material that directs a recipient’s cells to make spike, a surface protein from SARS-CoV-2, that then trains the immune system to respond to the virus. Novavax’s vaccine instead delivers the spike protein itself, carried on soaplike particles and given extra punch by an immune-boosting substance called an adjuvant. Protein technology has been used for decades in vaccines against diseases including hepatitis B.

In clinical trials so far, Novavax’s vaccine has produced somewhat fewer powerful, though transient systemwide side effects such as headache, muscle pain, and fatigue, which many recipients of the Pfizer-BioNTech and Moderna vaccines experienced. For instance, 54% of participants who received Moderna’s vaccine as part of a 30,000-person trial reported at least one such effect; in Novavax’s 15,000-person trial in the United Kingdom, that number was 38%.

After a second dose of vaccine in the North American Novavax trial, about 40% of participants who received the active vaccine reported experiencing some degree of headache, muscle pain, or fatigue. But serious reactions were rare.

Having relatively mild side effects is a plus, says Mayank Mamtani, a biotechnology analyst who follows Novavax for B. Riley Securities. “This Novavax vaccine is going to be less reactogenic. You don’t have to cancel all your meetings” afterward, he says. He adds that the Novavax jab may find a niche as a booster vaccine in the United States, where he says such boosters may be needed by October or November. “We in this country love choice,” he adds.  

Under its 2020 contract with Operation Warp Speed, Novavax committed to deliver 110 million doses to the U.S. government, although the country does not need them for initial vaccinations. Novavax expects to reach manufacturing capacity of 100 million doses per month by the end of the third quarter and 150 million doses per month by the fourth quarter of this year, Erck said.  

The company has advance-purchase orders for about 200 million doses from another five Western governments and last month signed a deal to supply Gavi, the Vaccine Alliance, with 350 million doses for the COVID-19 Vaccines Global Access (COVAX) Facility, a global vaccine-sharing partnership. The Serum Institute of India, which is also making the Novavax vaccine, is slated to deliver another 750 million doses to COVAX, Novavax says. Serum plans to start delivering the Novavax vaccine by September, provided regulatory agencies have authorized it, officials there told Science.

Novavax’s production projections are substantially dialed back from earlier company predictions that it would ship 2 billion doses this year. That reflects the company’s struggle to scale up its manufacturing both at its own facilities and those of contractors and partner companies in 11 nations. “Novavax has been particularly challenged with executing on production scale-up efforts and manufacturing,” Mamtani wrote in a note to investment clients last month.

Unlike mRNA vaccines, which need to be stored frozen, Novavax’s protein vaccine can be stored in a refrigerator for up to 6 months, and, once removed, remains viable for 24 hours. Novavax has created a new version of its vaccine, adapted to the Beta variant, that could be used as a 1-year booster, the company says. On Friday, it announced positive results for the adapted vaccine in mice and baboons. Novavax says it is also working to customize its vaccine to other SARS-CoV-2 variants.

But Samant cautions that Novavax’s manufacturing struggles and the entrenched advantages of companies whose vaccines were approved months ago may make the small company’s climb to market share and profitability a tough one.

Meredith Wadman