- German biotech CureVac plans to seek regulatory approval for its experimental coronavirus vaccine despite full results from a large international study confirming a disappointing overall efficacy against COVID-19 of just 48%.
- The final estimate, announced Wednesday evening, is little changed from the 47% interim figure disclosed by CureVac two weeks ago and is far lower than the high efficacy set by Pfizer, Moderna and, more recently, Novavax for their respective vaccines.
- CureVac, however, has emphasized the wider prevalence of coronavirus variants that threaten vaccine potency during the period in which it ran the trial. About half of the COVID-19 cases sequenced and included in the efficacy analysis were due to infections with so-called variants of concern, although only about 1% were the Delta variant that's now triggering alarm among public health officials worldwide.
CureVac is standing by its vaccine candidate, which company executives argue can still play an important role as more and more COVID-19 cases are attributed to shifting virus variants.
But despite the company's confidence, it's unclear whether the full results disclosed Wednesday will be enough to secure regulatory approval.
In the United States, the Food and Drug Administration has set a minimum bar of 50% vaccine efficacy and recently signaled the path for emergency authorization taken by Pfizer, Moderna and Johnson & Johnson is closing. Instead, the agency will favor that companies apply for standard approval, a longer process.
In Europe, meanwhile, regulators have not specified a percent efficacy they will use as a minimum bar for clearance. But they've also indicated they view 50% as a target.
"We intend to file for regulatory approval, leveraging [our vaccine's] demonstrated strength against the continuous variant dynamics and in populations where it can provide a great protection and serve the highest unmet need," said CureVac's CEO Franz-Werner Haas on a Thursday conference call.
The company noted it's communicated "available" data to the European Medicines Agency, with which it began a rolling submission of its vaccine back in February.
CureVac's latest data come from 228 cases of COVID-19 reported in its Phase 2b/3 study, which enrolled approximately 40,000 volunteers in Latin America and Europe. Eighty-three of those cases were among participants who had received two shots of CureVac's vaccine, while 145 were in volunteers given placebo. From those numbers, CureVac calculated a vaccine efficacy of 48%, although the company did not disclose confidence intervals around that estimate or figures used to measure the statistical strength of a comparison to placebo.
Among adults aged 18 to 60, CureVac reported a slightly stronger vaccine protection of 53% against COVID-19 of any severity and 77% against moderate or severe disease.
But only 21 cases were among adults older than 60, who made up about an eighth of the study's total enrolled participants. As a result, CureVac said it could not make a "statistically significant determination of efficacy."
The efficacy calculation did not include 360 cases of COVID-19 that were reported in the study but, according to CureVac executive Ulrike Gnad-Vogt, occurred prior to 15 days after those participants received a second shot. Similar to other vaccine trials, the study was designed to analyze efficacy after enough time had passed for immunization to have an effect.
"While the latter group of cases therefore did not contribute to the efficacy calculation, they help to provide a more accurate and extended picture of the circulating virus variants in the study," Gnad-Vogt said on Thursday's call. No further analyses on those cases are currently planned, she said.
CureVac sequenced 204 of the 228 COVID-19 cases it did use to calculate efficacy. Only 3% were attributed to the original virus strain that emerged in China late in 2019. More than half, 51%, were due to "variants of concern," and 35% were due to "variants of interest" — terms used to describe emerging strains that could, for various reasons, be more lethal or transmit more easily.
Against the Alpha variant, which was first identified in the U.K., efficacy was 55% in participants aged 18 to 60, CureVac said. That figure against Alpha is lower than what has been reported in clinical trials and real-world studies of vaccines from Pfizer and Novavax.
Efficacy against specific variants ranged from 42% to 67%, although the confidence intervals on each estimate are wide, suggesting the actual protection offered could differ significantly.
CureVac's vaccine caused side effects similar to those associated with Pfizer's and Moderna's vaccines, which use a similar technology. About half of participants reported fatigue, headaches or body aches after their second dose, although most instances were mild or moderate in degree.