CureVac looks to subgroup to save failed COVID-19 vaccine as final analysis confirms sub-50% efficacy

CureVac has highlighted the efficacy of its failed COVID-19 vaccine in adults aged up to 60 years as evidence the jab has a role to play in the response to the pandemic. The German biotech is pushing ahead with a regulatory submission in Europe despite achieving 48% efficacy in its phase 2b/3 trial.

Earlier this month, CureVac reported interim data linking its mRNA vaccine CVnCoV to 47% efficacy. At the time, Ulrike Gnad-Vogt, interim chief development officer at CureVac, said she expected the readout to change based on the addition of new cases to the final analysis. Two weeks later, the final analysis is available. The overall efficacy barely changed, rising one percentage point to 48%.

CureVac focused its release on the subset of patients aged 18 to 60 years. In that subgroup, the trial linked the vaccine to an efficacy of 53%. Efficacy against moderate to severe disease was calculated at 77% in the subgroup. 

In a statement, CureVac CEO Franz-Werner Haas said the data in 18 to 60 year olds demonstrate "a strong public health value” that shows CVnCoV “will be an important contribution to help manage the COVID-19 pandemic and the dynamic variant spread.” CureVac is in talks with the European Medicines Agency (EMA) and continuing with its regulatory submission.

Nine percent of the cases involved participants aged over 60 years. CureVac said “the available data did not enable a statistically significant determination of efficacy.” Removing cases included in the 18-to-60 analysis from the overall efficacy data set suggests there were more cases in vaccinated over-60s than in unvaccinated over-60s.

CureVac included the efficacy of CVnCoV in people aged 61 years and older as a secondary endpoint in the study protocol. However, the protocol lacks a secondary endpoint covering the 18-to-60 data CureVac is now pitching as evidence of the public health value of its vaccine.

It remains to be seen whether the EMA shares CureVac’s view. Existing vaccines achieved far higher efficacy levels in late-phase clinical trials, although any effort to compare results across studies is complicated by the explosion in SARS-CoV-2 variants since the likes of Moderna and Pfizer generated their data.

Eighty-six percent of the sequenced cases in CureVac’s final efficacy analysis involved variants of concern or interest. While all the variants differ from the original SARS-CoV-2 virus, only some of the mutations are expected to affect vaccine efficacy. Real-world data generated in the U.K. suggests the Pfizer-BioNTech vaccine is 93% effective at preventing symptomatic COVID-19 caused by the alpha variant. The efficacy of CVnCoV against different variants ranged from 42% to 67%.    

All of the CureVac analyses are based on the COVID-19 cases that met the adjudication criteria, which include assessments of whether the RT-PCR test was performed at the CureVac-designated central laboratory and whether symptoms occurred more than 15 days after the second vaccination. 

Most of the cases were excluded from the analyses on the basis of the adjudication criteria. CureVac sequenced samples from 588 COVID-19 cases, 204 of which met the criteria and were included in the efficacy analysis. The final analysis included 228 cases, up by 68 from the interim review. CureVac had previously said the final analysis would include “a minimum of 80 additional cases.”

Shares in CureVac fell 12% after the release of the final analysis.