BIMERVAX Emulsion for injection Ref.[50884] Active ingredients: SARS-CoV-2 spike glycoprotein (B.1 strains)

Pharmacotherapeutic group: Vaccines, Covid-19 vaccines
ATC code: J07BN

Mechanism of action

BIMERVAX is a recombinant protein vaccine whose active substance (antigen) is SARS-CoV-2 virus recombinant spike (S) protein receptor binding domain (RBD) fusion heterodimer – B.1.351-B.1.1.7 strains. Following administration, an immune response is generated, both at a humoral and cellular level, against the SARS-Co-V-2 RBD antigen. Neutralising antibodies against the RBD domain of SARS-CoV-2 prevent RBD binding to its cellular target ACE2, thus blocking membrane fusion and viral infection. Moreover, BIMERVAX induces antigen-specific T-cell immune response, which may contribute to protection to COVID-19.

Efficacy

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

Immunogenicity

The immunogenicity of BIMERVAX was evaluated in one pivotal phase 2b multi-centre clinical trial (Study HIPRA-HH-2) and in one phase 3 multi-centre clinical trial (Study HIPRA-HH-5).

Study HIPRA-HH-2

Study HIPRA-HH-2 is an ongoing phase 2b, double-blind, randomised, active-controlled, multicentre, non-inferiority clinical trial to assess immunogenicity and safety of a booster vaccination with BIMERVAX compared to tozinameran/COVID-19 mRNA Vaccine, in adults fully vaccinated against COVID-19 with a mRNA vaccine at least 6 months before enrolment. This phase 2b clinical trial excluded individuals who were pregnant, individuals who were immunocompromised or had received immunosuppressants within 12 weeks, as well as individuals with previous COVID-19 infection. Individuals were also required a minimum interval of 3 months after receipt of any immunotherapy (monoclonal antibodies, plasma) prior to the study.

A total of 765 subjects were vaccinated; 513 subjects received BIMERVAX, and 252 subjects received the COVID-19 mRNA vaccine (tozinameran). A total of 751 subjects were analysed (504 BIMERVAX subjects and 247 COVID-19 mRNA vaccine subjects) excluding those who tested positive for COVID-19 within 14 days of the booster. Randomisation was stratified by age group (18-64 versus ≥65 years). The median age was 42 years (range: 19 to 76 years), with similar age ranges in both vaccine arms, including 7.4% and 7.1% of subjects 65 years of age and older in the BIMERVAX and COVID-19 mRNA vaccine groups, respectively.

Immunogenicity of a booster dose of BIMERVAX was based on an assessment of geometric mean titres (GMT) of neutralising antibodies, measured by a pseudovirion-based neutralisation assay (PBNA) against SARS-CoV-2 (D614G) strain, Beta, Delta and Omicron BA.1 variants. GMT ratio is the result of the GMT values (ID50) of COVID-19 mRNA vaccine (tozinameran)/BIMERVAX. Noninferiority of BIMERVAX to COVID-19 mRNA vaccine (tozinameran) is concluded if the upper limit of the 2 sided 95% Confidence Interval (CI) of the GMT ratio is <1.4. Superiority of BIMERVAX to COVID-19 mRNA vaccine (tozinameran) is concluded if the upper limit of the 2-sided 95% Confidence Interval of the GMT ratio is <1.0 (see Table 2, GMT ratio column).

Table 2. Post-booster GMT ratio for BIMERVAX versus COVID-19 mRNA vaccine (tozinameran) with neutralisation titres (PBNA) against SARS-CoV-2 (D614G strain), Beta, Delta and Omicron BA.1 at days 14, 28, 98 and 182 post-booster dose (per protocol population):

N: number of participants in the population per-protocol.
Abbreviations: GMT = Geometric Mean Titre; CI: Confidence intervals; PBNA = pseudovirion-based neutralisation assay Non-inferiority of BIMERVAX to COVID-19 mRNA vaccine (tozinameran) is concluded if the upper limit of the 2-sided 95% Confidence Interval (CI) of the GMT ratio COVID-19 mRNA vaccine (tozinameran)/BIMERVAX is <1.4.
Superiority of BIMERVAX to COVID-19 mRNA vaccine (tozinameran) is concluded if the upper limit of the 2-sided 95% Confidence Interval of the GMT ratio COVID-19 mRNA vaccine (tozinameran)/BIMERVAX is <1.0.

HIPRA-HH-5

This study is an ongoing open label, single arm, multicentre, phase 3 clinical trial to assess the safety and immunogenicity of a booster vaccination with BIMERVAX for the prevention of COVID-19 in subjects vaccinated with several primary vaccine schedules, with or without previous non-severe COVID-19 infections. BIMERVAX was administered at least 91 days after the last dose or at least 30 days after the COVID-19 infection. This phase 3 clinical trial excluded individuals who were pregnant as well as individuals who were immunocompromised or had received immunosuppressants within 12 weeks. Individuals were also required a minimum interval of 3 months after receipt of any immunotherapy (monoclonal antibodies, plasma) prior to the study.

The interim report includes data from a total of 2 646 subjects who were vaccinated with BIMERVAX as a booster dose in healthy individuals (at least 16 years old) previously vaccinated with different COVID-19 vaccines (mRNA COVID-19 vaccines: tozinameran and elasomeran, and adenovirusvector vaccines (COVID-19 Vaccine (ChAdOx1-S [recombinant]) and COVID-19 vaccine (Ad26.COV2-S [recombinant]). Of these, 230 (8%) subjects were included in the immunogenicity population. In the immunogenicity analysis, the population of the Comirnaty/Comirnaty vaccine group were all subjects between 16-17 years old.

Overall, the median age was 34.4 years (range: 16 to 85 years of age). Subjects were balanced between genders, 52.49% male and 47.47% female.

Immunogenicity was measured by Pseudovirion-based neutralisation assay (PBNA) against SARS-CoV-2 (D614G) strain and against Beta, Delta and Omicron BA.1. Data on GMT (geometric mean titre: ID₅₀) at baseline (prior to the administration of the booster dose) and at Day 14 (2 weeks after the administration of the booster dose) are provided in the following table.

Table 3. Neutralising antibody Geometric Mean Titres (GMT) at 14 days post-booster with BIMERVAX in individuals 16 years of age and older-per protocol analysis:

N: Number of participants with available data for the relevant endpoint
Abbreviations: GMT = Geometric Mean Titre; CI: Confidence intervals

Elderly population

The immunogenicity of BIMERVAX has been shown in the elderly population (≥65 years old) including 38 (7.4%) of individuals receiving BIMERVAX.

Paediatric population

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