CureVac’s Flop Shows Pfizer, Moderna Made mRNA Look Too Easy

The rapid development and remarkable efficacy of Covid-19 shots from Pfizer Inc. and Moderna Inc. created sky-high expectations for the novel technology they employ. CureVac NV’s vaccine disappointment shows that not every messenger-RNA project will live up to hopes.

The German biotech firm made some crucial choices that set its candidate apart. Although the trial results it published earlier this week aren’t directly comparable, and the proliferation of viral variants has complicated studies since the other shots were tested last year, experts say key differences between the vaccines probably played a major role in CureVac’s weak results.

One key element was dosage. CureVac executives said they probably weren’t using enough mRNA to elicit strong immunity. The low dosing was necessary because the company was using a different type of mRNA from the kind in rival shots, and higher amounts would have raised the risk of side effects.

The company lost more than half of its market value after it disclosed that the vaccine was only 47% effective against Covid infections in an interim analysis. The shares regained a bit of that Friday, rising 10% in premarket U.S. trading.

The efficacy rate is far below the levels hit by Moderna and Pfizer. While it’s too early to call the CureVac shot a failure, the weak preliminary results have thrown the company’s choices into question, suggesting that virus variants alone may not account for the vaccine’s poor performance relative to rivals.

CureVac’s Flop Shows Pfizer, Moderna Made mRNA Look Too Easy

“It’s a big surprise,” said Zhiqiang Shu, an analyst with Berenberg Capital Markets LLC. “I would attribute a lot of that to the technology,” Shu said.

Next Generation

If CureVac can’t get approval for its first-generation vaccine, it will be more difficult to push through clinical trials for a more promising second-generation version of the shot, Shu said.

That version should be more potent even if the mRNA is not modified, the company said, because of optimization of the formula. Still, it pointed toward new variants for the “sobering” results of its study, saying the landscape has changed since others conducted their tests.

“There was room for improvement for the technology” in the context of developing a second-generation Covid shot, CureVac spokeswoman Sarah Fakih said. “We could also discuss about whether it was the best candidate. But the results don’t have a read-through into the technology not working.”

Like the approved shots from Moderna and Pfizer, which worked in partnership with BioNTech SE, CureVac’s candidate relies on mRNA to enlist the body’s own cells as vaccine factories. But the products occupy competing camps in the emerging world of that technology.

CureVac’s Flop Shows Pfizer, Moderna Made mRNA Look Too Easy

The immune system quickly tries to attack free-floating unmodified mRNA that’s in the body, forcing drug developers to mask their products so they aren’t destroyed before they can be effective. Moderna and BioNTech do this by making chemical modifications. CureVac, on the other hand, leaves the mRNA in a more natural state.

CureVac’s approach may have upsides, if it can be honed in the next generation of the vaccine. The biotech used only 12 micrograms of mRNA in its shot, potentially allowing the same amount of the substance to stretch for far more doses of vaccine. By contrast, each dose of the Pfizer-BioNTech shot has 30 micrograms of mRNA, while Moderna’s requires 100.

Dosing Levels

But CureVac’s shot probably failed to protect effectively against Covid because these dosing levels were too low, said Peter Kremsner, director of the Institute of Tropical Medicine at the University of Tuebingen in Germany, who helped supervise the patient trial. The company couldn’t use a higher dosage because it didn’t modify the mRNA in the formulation, Kremsner said in an email.

An earlier trial showed that CureVac’s dosage generated an amount of antibodies similar to those of patients recovering from a natural Covid infection after two weeks, while the level for Moderna and Pfizer’s shots was three times higher, said Sam Fazeli, an analyst with Bloomberg Intelligence.

“Blaming virus variants for the low efficacy of CureVac’s vaccine is dangerous and ill-considered,” Fazeli wrote, saying that could hamper inoculation drives and lead people to be unnecessarily anxious.

Despite the setback, CureVac says it will keep going and seek regulatory approval because more vaccines are needed. A full analysis of the age groups and different variants in the trial will be needed, European Medicines Agency officials said on Thursday.

CureVac investor Dietmar Hopp, a co-founder of software giant SAP SE, said in an interview with that the company “will be successful” and he “will definitely stay as an investor.” Hopp owns 47% of CureVac.

The data comes as the world is at a crossroads in the pandemic, with global infections falling even as flare-ups in places with less access to vaccines serve as a reminder that Covid is far from gone. The wealthiest countries have taken an outsize share of the more than 2.4 billion shots administered so far.

Bayer, GSK

Partly owned by the German government, CureVac has forged partnerships with Bayer AG, GlaxoSmithKline Plc and the U.K. government aimed at speeding production of its shot and future versions that will target mutated strains.

More details will emerge in the final readout of the study, which will include more than 200 cases and could come within two or three weeks. New data could change the efficacy results, CureVac said.

“We are virtually fighting a different virus, a different pandemic, over the last six months,” Chief Executive Officer Franz-Werner Haas said on a conference call.

©2021 Bloomberg L.P.

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