CureVac's COVID-19 Vaccine Demonstrates Interim Efficacy of 47%

The biotechnology company CureVac has announced that its Phase IIb/III clinical trial of the COVID-19 vaccine candidate CVnCoV demonstrates an interim efficacy of 47%.

mRNA vaccines

Pfizer–BioNTech's BNT162b2 was the first mRNA-based vaccine in history to receive authorization. It is also anticipated to be the first of many mRNA vaccines, as the platform offers several advantages over "traditional" approaches, including increased flexibility for manufacturing at large scale. Other mRNA-based vaccines for COVID-19 are currently situated at earlier stages in the development pipeline, including CureVac's CVnCoV, which first entered human clinical trials in June 2020. Though not yet approved, there was anticipation that this vaccine could overcome some of the current challenges facing global vaccination efforts, including cold-storage and supply issues. Compared to its authorized mRNA vaccine counterparts, CVnCoV can be stored at standard refrigerator temperatures (5 °C). In addition, the mRNA material in the vaccine is not chemically modified, arguably making its production quicker and less complex compared to its mRNA-based vaccine siblings. It is also administered at a dose of 12 µg, compared to the higher doses required for Pfizer–BioNTech's BNT162b2 (30 µg) and Moderna's mRNA-1273 (100 µg).

However, CureVac has announced that the results from a second interim analysis of its randomized placebo-controlled Phase IIb/ III study, the HERALD trial, demonstrated an interim efficacy of 47% for CVnCoV, meaning the trial has not met its prespecified statistical success criteria.

What is an interim analysis?

An interim analysis involves reporting on data that is available in a clinical trial or scientific study before the full data collection is complete. Such studies, particularly when large in size, require substantial amounts of resources and funding. An interim analysis helps to provide insight as to whether the study is worth this investment, in a manner that is free from conflict of interest.

The HERALD study

The HERALD study, conducted in collaboration with pharmaceutical company Bayer, recruited ~40,000 participants from 10 countries in Latin America and Europe. Subjects were randomly allocated to receive either two 12 µg doses of CVnCoV or a placebo solution 29 days apart. The announcement from CureVac states that the interim efficacy of 47% is against COVID-19 disease "of any severity".

“The data presented so far only relate to prevention of disease 'of any severity'," Dr Peter English, retired consultant in communicable disease control, told the Science Media Centre. "We know that the other COVID-19 vaccines (and this is generally true for vaccines) are more effective at preventing more severe outcomes." He added that the efficacy of the vaccine in preventing severe illness or death could be "considerably higher".

Dr Franz-Werner Haas, chief executive officer of CureVac, said that the company is "continuing toward the final analysis with a minimum of 80 additional cases" which he suggests could result in a change in the vaccine efficacy. Commenting on this additional data, medicinal chemist Derek Lowe implied that such change could be a further decrease: "The slides that have been released this morning show that there are still a number of cases that are being evaluated, so that number [47% efficacy] is very likely to go down."

The impact of variants

CureVac states that 134 COVID-19 cases were analyzed as part of the interim evaluation, of which 124 were genetically sequenced to identify the specific SARS-CoV-2 variant that caused the infection. Of the 124 samples sequenced, just one case was determined as being caused by the "original" SARS-CoV-2 virus; 57% were attributed to Variants of Concern (VOCS). “While we were hoping for a stronger interim outcome, we recognize that demonstrating high efficacy in this unprecedented broad diversity of variants is challenging," Haas said.

"CureVac has spent a lot of time in its public statements talking about the variants that its trial ran into and saying that these are the reason for the lower efficacy. Implicit in that is the idea that if you ran the other two mRNA vaccines in a trial right now, you’d come out with similar numbers," Lowe said, adding that he has trouble believing that this would be the case. "The real-world protection that we’re seeing in mRNA-vaccinated populations simply does not reflect an underlying efficacy in the 40% range. That’s the biggest argument right there."

CureVac states it is "committed to COVID-19 vaccine development", and – in addition to CVnCoV – is working on second-generation COVID-19 vaccines in partnership with GlaxoSmithKline.