Big Pharma Is Racing to Bolster Its Vaccines Against Variants

Yet pharma companies now suddenly face a daunting challenge that few anticipated we’d see so soon: an onslaught of fast-spreading and potentially dangerous mutations of the virus. So even as they ramp up production in the early stages of a massive rollout, drugmakers have to retool their vaccine strategies. That’s raised the possibility that patients will need extra shots to protect against the new strains—and that drugmakers could get a new revenue stream that, for some, may prove lucrative.

The highly transmissible B.1.1.7 mutation first identified in the U.K. is spreading across the U.S. But the strains researchers are most worried about come from South Africa and Brazil. The South African variant has spread quickly across Africa and has been seen in at least 24 countries elsewhere. It was reported in South Carolina on Jan. 28 and in Maryland two days later. The strain prominent in Brazil shares one of the same key mutations.

Current Covid vaccines are formulated to fight the form of the virus that was most prevalent last year. But small changes occur as the virus replicates, so as the pathogen spreads, it mutates into viruses the original vaccines might not be properly tailored to fight. The world has “allowed the virus to infect 100 million people already,” says virologist David Ho, who heads the Aaron Diamond AIDS Research Center at Columbia University. “That is 100 million chances for mutation.”

If that sounds terrifying, scientists say it should be manageable with either new strain-specific vaccines or booster shots. It’s also likely to be good for business. “It is increasingly likely” that wrangling the virus with a series of booster shots will translate into a sustained revenue stream for drugmakers, Pfizer Inc. Chief Executive Officer Albert Bourla said on a Feb. 2 call with investors. When Moderna Inc. said on Jan. 25 that it was working on a pair of booster shots, its share price increased 12%.

Meanwhile, AstraZeneca Plc and its partner, the University of Oxford, plan to have a revised version of their vaccine tailored to new variants available by fall, researchers involved said on Feb. 3. The same day, Germany’s CureVac NV and British drug giant GlaxoSmithKline Plc announced a €150 million ($180 million) pact to devise next-generation messenger RNA vaccines against emerging variants.

Clearly, there’s money to be made in booster shots. Industry leaders and analysts have been talking about Covid boosters in terms similar to those used to describe the market for flu shots, those never-ending annual jabs that go into hundreds of millions of arms around the globe. Morgan Stanley analyst Matthew Harrison estimates the yearly market for Covid vaccine booster shots could range from $5 billion to almost $23 billion. It’s impossible to give a more precise estimate, because no one knows how widely mutations that evade the vaccines’ effectiveness will spread or what proportion of people in each country will need to be vaccinated.

Until recently, the evidence that vaccines were less potent against some of the variants was mostly lab-based. Tests showed vaccines from Pfizer and Moderna produced much lower levels of so-called neutralizing antibodies against the South African strain. In one study, scientists from the Aaron Diamond AIDS Research Center found that the Pfizer and Moderna vaccines were 6.5 to 8.6 times less potent against the mutation. Still, the companies have said that even these reduced antibody levels should be high enough to hold the strain at bay.

Then late-stage trials of vaccines developed by Johnson & Johnson and Novavax Inc. came out. They showed their shots to be highly potent against the original forms of the virus. But results from studies done in South Africa told a less impressive tale. The J&J shot was found to be 72% effective in the U.S., but that fell to 57% in South Africa. Novavax’s shot, 89% effective in the U.K., was only 49% effective in South Africa. Those results are “sobering,” says Eric Topol, director of the Scripps Research Translational Institute in San Diego. “We see an unequivocal drop-off in efficacy.”

That means vaccine makers are now diverting attention to work on either booster shots or a new, adjusted vaccine that can work better against the South African mutation, known scientifically as B.1.351. “We are having enough of a struggle getting the first round of vaccines in,” Topol says.

Pfizer contends its existing vaccine can handle the variants, because it produces high levels of antibodies. Still, the company plans to start studies of a third booster shot of its existing vaccine as well as a customized booster against new strains. The extra shot would be given six months to a year after the first two doses. If booster shots continue to be needed after the pandemic is over, Pfizer will likely get a higher price for the follow-up vaccine, executives said on its Feb. 2 investor call. The difference in pricing could be substantial. Pfizer is selling its Covid vaccine to the U.S. for $19.50 per dose, meaning $39 for the full regimen. For normal vaccines, the company gets around $150 to $175 a dose.

Moderna said it also will begin work on two booster shots, including one targeted to neutralize the South African strain. The booster may work at a lower dose than Moderna’s existing vaccine, meaning Moderna could potentially make as much as eight times as many booster doses with its existing manufacturing footprint. Meanwhile, Johnson & Johnson and Novavax have also said they’re looking into approaches that could help fight the South African strain.

Details and timing for the booster shot studies are still being worked out, but they likely won’t require big trials on thousands of people as the first round of vaccines did. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said during an American Medical Association webinar that the agency is seeking to finalize a playbook with the industry to address mutations.

If the agency feels the virus has drifted enough to require a different sequence, it will need small trials to make sure the vaccines produce an immune response, he said. The first few studies may have to go through an advisory committee, but the agency is looking to streamline the process as much as possible and may require less data over time. “We would intend to be pretty nimble with this,” Marks said, “so we get these variants covered as quickly as possible, because it is clear they can spread pretty quickly.”

So for now, it’s a race to vaccinate the U.S. and Europe before the South African variant becomes more common, or, worse yet, if new mutations enable the virus to escape existing vaccines. If health experts and drugmakers fail to get their arms around the mutation conundrum, Anthony Fauci, the top U.S. infectious disease expert, said on Feb. 2, the timetable for ending the pandemic “could change dramatically.” —With Jeannie Baumann, Cristin Flanagan, and Emma Court

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