VIDPREVTYN BETA Solution and emulsion for emulsion for injection Ref.[50347] Active ingredients: SARS-CoV-2 spike glycoprotein (B.1 strains)

Pharmacotherapeutic group: Vaccine, other viral vaccines
ATC code: J07BX03

Mechanism of action

VidPrevtyn Beta is an adjuvanted vaccine composed of the soluble trimeric SARS-CoV-2 recombinant spike (S) protein (B.1.351 strain) stabilised in its prefusion conformation and deleted of its transmembrane and intracellular domains. The combination of antigen and adjuvant enhances the magnitude of immune response, which may contribute to protection against COVID-19.

Immunogenicity

Efficacy of VidPrevtyn Beta has been inferred by immunobridging of immune responses to an authorised COVID-19 vaccine, for which vaccine efficacy has been established.

The clinical immunogenicity of VidPrevtyn Beta given as a first booster injection is being evaluated in two clinical studies: VAT00013 (Study 1) in COVID-19 mRNA vaccine-primed participants and VAT00002 Cohort 2, Beta arm (Study 2) that included participants primed with various types of COVID-19 vaccines.

Immunogenicity results from Study 1

Study 1 is a randomised, single-blinded multicenter investigator-initiated clinical study, which evaluated the immune response induced by a booster dose of either VidPrevtyn Beta or COVID19 mRNA vaccine (nucleoside modified/tozinameran) in individuals previously vaccinated with 2 doses of COVID-19 mRNA vaccine (tozinameran). The per-protocol analysis population included 143 participants 18 years of age and older primed with 2 doses of COVID-19 mRNA vaccine (tozinameran) 3 to 7 months prior to receiving VidPrevtyn Beta (N=67), COVID-19 mRNA vaccine (tozinameran) (N=76). The mean age was comparable across groups with 41.4 and 40.4 years for VidPrevtyn Beta and COVID-19 mRNA vaccine (tozinameran), respectively. Age ranged from 20.0 to 69.0 years. The mean duration between the second dose of the primary series and the booster dose was comparable across groups, being 171.0 and 174.5 days for VidPrevtyn Beta and COVID-19 mRNA vaccine (tozinameran), respectively.

Among this per-protocol population, samples from prior to vaccination and 28 days after booster of 114 participants (54 from VidPrevtyn Beta and 60 from COVID-19 mRNA vaccine (tozinameran)) were tested by Pseudovirus Neutralisation Assay. The Geometric Mean Titers (GMT) of neutralising antibodies 28 days after VidPrevtyn Beta or COVID-19 mRNA vaccine (tozinameran) booster in COVID-19 mRNA vaccine-primed participants were compared.

Superiority of GMT against Omicron BA.1 was demonstrated for VidPrevtyn Beta group in comparison with COVID-19 mRNA vaccine (tozinameran) group, see Table 2.

Table 2. Post-booster GMT ratio for VidPrevtyn Beta versus COVID-19 mRNA vaccine (tozinameran) with individual neutralisation titres against Omicron BA.1 – 28 days postbooster dose – per-protocol analysis subset:

M: number of participants with available data for the relevant endpoint;
N: number of participants in per-protocol analysis subset 28 days post-booster dose;
^† Superiority is concluded if the lower limit of the 2-sided 95% Confidence Interval (CI) of the GMT ratio >1.2.

Non-inferiority of seroresponse rate against Omicron BA.1 and D614G strains for VidPrevtyn Beta compared to COVID-19 mRNA vaccine (tozinameran) was demonstrated (see Table 3). Seroresponse rate was defined as a 4-fold or greater rise in serum neutralisation titre 28 days postbooster dose relative to pre-booster dose.

Table 3. Seroresponse rate (SR) for VidPrevtyn Beta versus COVID-19 mRNA vaccine (tozinameran) with individual neutralisation titre against Omicron BA.1 and D614G – 28 days post-booster dose – per-protocol analysis subset:

M: number of participants with available data for the relevant endpoint;
N: number of participants in per-protocol analysis subset 28 days post-booster dose;
n: Number of participants who achieve seroresponse;
^† Non-inferiority is concluded if the lower limit of the 2-sided 95% Confidence Interval (CI) of the difference in seroresponse rate between groups is > -10%.

Levels of neutralising antibody titres against D614G 28 days post-booster dose observed in VidPrevtyn Beta group were higher than in COVID-19 mRNA vaccine (tozinameran) group, with the GMT ratio of 1.43 (95%CI 1.06; 1.94), see Table 4.

Table 4. Neutralising antibody Geometric Mean Titres (GMT) against D614G – 28 days postbooster dose – per-protocol analysis subset:

N: number of participants in per-protocol analysis subset 28 days post-booster dose;
CI: Confidence Interval

Immunogenicity results from Study 2

VidPrevtyn Beta given as a booster is being evaluated in an ongoing multicentre phase 3 clinical study in participants 18 years of age and older. Per-protocol analysis population included 543 participants who received VidPrevtyn Beta 4 to 10 months after receiving primary vaccination with 2 doses of COVID-19 mRNA vaccine (tozinameran) (n=325) or COVID-19 mRNA Vaccine (nucleoside modified/elasomeran) (n=93), COVID-19 Vaccine (ChAdOx1-S [recombinant]) (n=94), or with 1 dose of COVID-19 vaccine (Ad26.COV2-S [recombinant])(n=31).

In the per-protocol analysis population primed with mRNA vaccines and receiving VidPrevtyn Beta booster, the mean age of participants was 41.2 years (range 18-83 years); 347 (83.0%) were 18 to 55 years of age, 71 (17.0%) were 56 years of age and older, 25 (6.0%) were 65 years of age and older. Among them, 44.0% were male, 56.0% were female, 67.7% were White, 13.2% were Black or African American, 2.6% were Asian, and 1.0% were American Indian or Alaska Native.

In the per-protocol analysis population primed with adenoviral vector vaccines and receiving VidPrevtyn Beta booster, the mean age of participants was 50.4 years (range 24-77 years); 84 (67.2%) were 18 to 55 years of age, 41 (32.8%) were 56 years of age and older, 17 (13.6%) were 65 years of age and older. Among them, 52.8% were male, 47.2% were female, 78.4% were White, 13.6% were Black or African American, 4.0% were Asian, and 2.4% were American Indian or Alaska Native.

Immunogenicity was assessed by measuring neutralising antibody titres (ID50) against a pseudovirus expressing the SARS-CoV-2 Spike protein from a USA_WA1/2020 isolate with the D614G mutation and B.1.351 variant using a SARS-CoV-2 Pseudovirus Neutralisation Assay.

A booster response to VidPrevtyn Beta was demonstrated regardless of the vaccine used for primary vaccination with the Geometric Mean Titres Ratio (GMTR, fold increase) 14 days postbooster relative to pre-booster against B.1.351 strain ranging from 38.5 to 72.3, and from 14.5 to 28.6 for D614G strain, see Table 5.

Table 5. Neutralising antibody Geometric Mean Titres (ID50) at 14 days post-booster dose and Geometric Mean Titres Ratio (14 days post-booster dose relative to pre-booster dose) against a pseudovirus expressing the SARS-CoV-2 Spike protein in participants 18 years of age and older – per-protocol analysis set:

M: number of participants with available data for the relevant endpoint;
N: number of participants in per-protocol analysis set
CI: Confidence Interval
ID50-serum dilution conferring 50% inhibition of pseudovirus infection
GMTR (geometric mean titre ratio): geometric mean of individual titre ratios (post-vaccination/pre-vaccination)
^1-2 - Priming vaccines: 1 – COVID-19 mRNA vaccine (tozinameran) and COVID-19 mRNA vaccine (elasomeran); 2 – COVID-19 Vaccine (ChAdOx1-S [recombinant]) and COVID-19 vaccine (Ad26.COV2-S [recombinant])

Paediatric population

The European Medicines Agency has deferred the obligation to submit the results of studies with VidPrevtyn Beta in one or more subsets of the paediatric population in prevention of COVID-19 (see section 4.2 for information on paediatric use).