begun a phase 2b/3 clinical trial of its COVID-19 vaccine candidate CVnCoV. The study will enroll 36,500 participants in Europe and Latin America with a view to generating data to support approval of the mRNA vaccine next year.CureVac has
BioNTech, working with Pfizer, and Moderna have validated the concept of using mRNA to provide protection against SARS-CoV-2, rapidly delivering stellar efficacy results that set a high bar for the rest of the field. CureVac has taken a slightly different approach to mRNA vaccines, choosing to use the potency of untranslated regions to optimize the RNA rather than make chemical modifications.
The approach has created a candidate that triggers immune responses at a 12-µg dose, compared to the 100 µg used by Moderna. That will enable CureVac to make more doses of the vaccine. CureVac is also aiming to trigger balanced immune responses.
CureVac is now putting its approach to the ultimate test. The phase 2b portion of the clinical trial will randomize 4,000 subjects across two age cohorts—18 to 60 years and 61 years and older—to take two doses of CVnCoV or placebo four weeks apart. Around 800 to 1,000 of the participants will be aged 61 years and older.
The phase 2b trial will generate safety, reactogenicity and immunogenicity data to inform the start of the phase 3. Once 1,000 subjects have at least one week of follow-up after the first vaccination, the Data and Safety Monitoring Board will review the data and make a decision on the phase 3.
CureVac plans to move seamlessly into the phase 3 clinical trial if the data support the larger study. The phase 3 study will recruit 32,500 subjects. CureVac plans to pool data from the phase 2b and 3 portions of the clinical trial.
The co-primary endpoints of the trial cover prevention of all COVID-19 cases and just severe cases. The first interim review is set to take place when 56 people have developed COVID-19, with later reviews scheduled for 111 and 185 cases. CureVac estimates the first review will take place around five months after the first vaccination. If seven cases or fewer are in the CVnCoV arm at that point, CureVac will be able to claim success and likely start preparing for regulatory filings.
Given the phase 3 results from other mRNA vaccines, it would be surprising if CureVac’s candidate is completely ineffective. However, as AstraZeneca has found, BioNTech, Pfizer and Moderna have reset expectations for COVID-19 vaccines. CureVac will need 90%-plus efficacy and a good safety profile to join the top tier of COVID-19 vaccines.
Based on the available data, and with the caveat that cross-trial comparisons can be unreliable, the CureVac candidate appears to trigger roughly comparable immune responses to other vaccines but have a somewhat worse tolerability profile. A higher proportion of subjects who received 12 µg of CVnCoV had moderate to severe fever, headache and fatigue than was seen in the BioNTech-Pfizer phase 3, although the CureVac results come from a small cohort presented last month.