Long awaited Phase IIb/III results for a third mRNA COVID-19 vaccine developed by German biotech CureVac, with support from Bayer, have proved disappointing with a secondary interim result showing only 47% efficacy, a figure well below that of BioNTech/Pfizer and Moderna’s mRNA vaccines.
This interim analysis is based on 134 cases, but the company plans to make a final analysis in 2–3 weeks when 200 cases are reached. While this analysis is not final, and the company is waiting until then to make any important development decisions, these late interim results do not look promising for CureVac’s first-generation COVID-19 vaccine candidate.
The efficacy shown so far for the CvnCoV vaccine is very low, despite using similar technology to BioNTech/Pfizer and Moderna’s mRNA vaccines that both boast efficacy of more than 90% for most population groups. In a statement to the press and investors, the company says an increased number of virus variants and mild cases may have contributed to the poor result.
“While we were hoping for a stronger interim outcome, we recognize that demonstrating high efficacy in this unprecedented broad diversity of variants is challenging. As we are continuing toward the final analysis with a minimum of 80 additional cases, the overall vaccine efficacy may change,” said Franz-Werner Haas, CEO of CureVac.
However, Novavax’s Phase III vaccine trial—carried out during the same time period— announced efficacy of over 90% against 13 different recent variants earlier this week, potentially weakening any claims that variants might be to blame for the poor efficacy of the CvnCoV vaccine.
The international Phase IIb/III HERALD study enrolled approximately 40,000 participants in 10 countries in Europe and Latin America. The secondary interim analysis included 134 COVID-19 cases occurring at least 2 weeks after the second doses of the vaccine were administered. The first generation CVnCoV vaccine had 47% efficacy for prevention of COVID-19 cases of any severity across all strains and was more effective in the 18–60 years group, according to the statement.
As many variants are now in circulation, the study investigators are monitoring and sequencing variants causing COVID-19 cases in the trial population. Overall, 124 of the 134 cases included in the secondary analysis were sequenced. The researchers found that 57% of the cases were caused by so called “variants of concern.” Of the remaining cases sequenced, 21% were caused by the Lambda or C.37 variant, first identified in Peru, and 7% by a variant first identified in Columbia known as B.1.621, as well as a few other strains.
While the announcement is undoubtedly disappointing, dropping more than $8 billion off the company’s market cap after the markets opened yesterday, CureVac plans to continue COVID-19 vaccine development and has high hopes for its second-generation mRNA candidate that it is developing with GSK.
This second-generation candidate should start human trials in the third quarter of this year and has already shown better efficacy than CVnCoV in initial testing, according to company representatives presenting the trial information on a webcast and conference call earlier today. If the trials go well, CureVac and GSK are hoping for approval in 2022.
The new candidate has a different mRNA backbone from CVnCoV, generated on the basis of the vaccine research and development the company has carried out over the last year, and in initial studies shows increased and extended protein expression, as well as a faster onset of neutralizing antibody production and increased overall immunogenicity, compared with CVnCoV.