Valneva Trial Compares New COVID-19 Vaccine to Oxford–AstraZeneca Vaccine
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Valneva has announced topline results from its Phase III trial of the inactivated, adjuvanted COVID-19 vaccine candidate VLA2001.
A inactivated, whole virus COVID-19 vaccine
VLA2001 is an inactivated whole virus vaccine that utilizes Valneva's "Vero-cell" platform technology. The platform is currently used in the commercialized vaccine IXIARO®. The vaccine contains the entire SARS-Cov-2 virus, which is grown in a cell culture before being inactivated via chemical means. This process preserves the native structure of the antigen (the S protein of the SARS-CoV-2 virus) that is then able to trigger an immune response upon administration.
Such response is enhanced by the inclusion of two adjuvants – Alum and CpG1019 – which are also used in currently available vaccines. At present, VLA2001 is the only vaccine of its kind being developed in Europe. "This is a much more traditional approach to vaccine manufacture than the vaccines so far deployed in the UK, Europe and North America," Adam Finn, professor of pediatrics at the University of Bristol and chief investigator of the trial said in a press release.
"[The vaccine is] intended for active immunization of at-risk populations to prevent carriage and symptomatic infection with COVID-19 during the ongoing pandemic," Thomas Lingelbach, chief executive officer of Valneva said in a press conference. He added that VLA2001 may also be a particularly suitable for booster vaccinations, as this type of vaccine (whole virus inactivated) has historically proven to work well as a booster in other infectious diseases.
The Cov-Compare trial
The trial – named Cov-Compare – was a randomized, observer-blind study that recruited over 4,000 people across 26 different sites in the UK. The primary objective was to compare the immunogenicity – i.e., the ability to produce an immune response – of VLA2001 with the Oxford–AstraZeneca vaccine, AZD1222 (formerly named ChAdOX1). This outcome was quantified by the geometric mean titer (GMT) of antibodies produced in participants. The second primary outcome measure of the trial was the frequency and severity of any adverse events occurring in response to either vaccine.
Cov-Compare recruits were divided into two separate groups: 2,972 participants aged 30-years and over were randomized to receive either two intramuscular doses of VLA2001 (n= 1977) or AZD1222 (n=995) at the recommended dose level for each vaccine, 28 days apart. To determine safety and tolerability profiles in younger populations, a further 1,040 participants aged between 18-29 years and over were recruited and assigned to receive VLA2001 in an open-label fashion.
In its announcement, Valneva stated that the trial has met its co-primary endpoints. The only data that has been made available by the company is in the form of a press release, and so it is important that the conclusions are interpreted with care.
"VLA2001 demonstrated superiority against AZD1222 (ChAdOx1-S) in terms of geometric mean titer for neutralization antibodies (GMT ratio=1.39, p<0.0001)," the press release states. The GMT for the VLA2001 group was 803.5 (95% CI: 748.48, 862.59), in comparison to the AZD1222 group, which had a GMT value of 576.6 (95% CI 543.6, 611.7) two weeks after the second vaccination (day 43 of the trial) in adults aged 30-years and over. In addition, VLA2001 demonstrated non-inferiority in terms of seroconversion rate (SCR) when compared with AZD1222, as an SCR above 95% was recorded for both treatment groups.
Commenting on the results, Dr. Peter English, retired consultant in communicable disease control, said, "In terms of laboratory assessment of efficacy, Valneva produced higher levels (as measured by GMT than ChAdOx1-S. The clinical and epidemiological significance of this has yet to be seen."
He added, "In terms of preventing infection, you need enough antibodies; the benefit of additional levels of antibody is more in terms of the expected duration of protection. If there is a threshold level above which you are protected, the higher the level induced by vaccination, the longer it is likely to be (since antibody levels decay in an approximately linear way) until you lose immunity to infection."
VLA2001 also triggered the production of T cells in a smaller proportion of participants that were reactive against the S-, N- and M- proteins of the SARS-CoV-2 virus. Valneva also states that VLA2001 was generally well tolerated, demonstrating a tolerability profile that was "significantly more favorable" when compared to the Oxford–AstraZeneca vaccine.
Professor Penny Ward, independent pharmaceutical physician and visiting professor in Pharmaceutical Medicine at King’s College London, said: "As the results have been shared in the form of a press release, detailed information is not available, but based on the data provided it is reasonable to expect that the Valneva vaccine will be at least as effective in clinical use, perhaps more so if the apparently superior immune response is sustained across all patient groups, including the elderly and immune compromised."
In a press conference, Valneva stated that the number of COVID-19 cases across the VLA2001 group and the AZD1222 group were "similar". The company could not disclose the exact number of confirmed COVID-19 at this stage as there are confirmations outstanding, Lingelbach said.
What is next for VLA2001?
"Today's results follow the Phase I/II results that we reported back in April 2021. Since that time, we have initiated rolling submissions to the MHRA and we have initiated extensions of the ongoing studies (Phase I/II study and the Phase III study)," Lingelbach said.
Despite the Cov-Compare trial taking place in the UK, it's unclear at this stage what role – if any – VLA2001 will play in the UK'S COVID-19 vaccination strategy. In September, Valneva announced that the UK Government had terminated its contract with the biotech company, citing "a break of the Supply Agreement", which Valneva "strenuously" denied.