Bexsero: first meningitis B vaccine launched

PHARMACOLOGY

Bexsero is a meningococcal group B vaccine containing Neisseria heparin binding antigen (NHBA), Neisserial adhesin A (NadA) and factor-H binding protein variant 1 (fHbp), combined with outer membrane vesicles (OMV) from Neisseria meningitidis group B strain NZ98/254. It is expected to elicit protective antibodies against an estimated 78% of meningococcal group B isolates.¹ 

CLINICAL STUDIES

The ability of Bexsero to induce serum bactericidal antibody responses to NadA, fHbp, NHBA and the OMV antigen PorA P1.4 was assessed in immunogenicity studies, as a surrogate measure of vaccine efficacy. 

A total of 3,630 infants were enrolled in a phase III multicentre study of the vaccine. In the open-label immunogenicity substudy, 2,627 infants were randomised to receive routine vaccinations (pneumococcal conjugate and DTaP-IPV-Hib-hepatitis B) at two, four and six months of age, with or without Bexsero. In the observer-blind safety substudy, 1,003 infants were randomly assigned to receive routine vaccines, plus either Bexsero or meningococcal serogroup C (MenC) vaccine.² 

Protective antibodies

In total, 100% (95% CI 99–100) of infants who received Bexsero in the immunogenicity study achieved human complement serum bactericidal activity (hSBA) titres ≥5 against fHbp and NadA indicator strains one month after having received the last vaccine dose. The majority of infants (84%; 95% CI 82–86) achieved hSBA titres of ≥5 against the New Zealand OMV indicator strain. Lower limits of the 95% CIs for the percentages of patients with hSBA titres ≥5 were greater than 70% for all three reference strains, thereby meeting the predefined criteria of a sufficient immune response.² 

An open-label extension study enrolled 1,555 infants from the Bexsero groups, who were randomised to receive either a fourth (booster) dose of the vaccine at 12 months, along with the measles, mumps, rubella and varicella vaccine (MMR-V), or Bexsero alone. Analysis showed that 95–100% of children had subsequent hSBA titres of ≥5 for all Bexsero antigens, regardless of concomitant MMR-V immunisation. Immune responses to routine vaccines were not significantly altered by Bexsero, although concomitant vaccination was associated with increased reactogenicity.³ 

Injection site reactions

The most frequent local reaction after primary immunisation was injection site tenderness, which occurred in 87% of Bexsero recipients (vs 59% for pneumococcal vaccine and 68% with pneumococcal vaccine plus MenC vaccine). Fever (≥38.5°C) was the most notable systemic reaction, occurring within six hours in 65% of infants after receiving Bexsero, compared with 32% of those receiving routine vaccination, and 32% after routine vaccination plus MenC. The occurrence of febrile seizures and the proportion of infants receiving antipyretics were similar to those reported in other combination vaccine studies.³ 

An open-label Phase IIb study in 1,885 infants showed that Bexsero was immunogenic when administered with routine vaccinations at two, four and six months or in an accelerated schedule at two, three and four months. Bexsero did not markedly affect the responses to the routine vaccines.^1,2

Immunogenicity of Bexsero vaccine was also demonstrated in older children, adolescents and adults.¹ 

JCVI decision

Earlier this year, the Joint Committee on Vaccination and Immunisation (JCVI) concluded that current evidence is insufficient to support a recommendation for the introduction of Bexsero as a routine adolescent immunisation.⁴

References:         

1. Bexsero Summary of Product Characteristics, Jan 2013.
2. Gossger N et al. JAMA 2012; 307: 573–82.
3. Vesikari T et al. Lancet 2013; 381: 825–35.
4. JCVI interim position statement on use of Bexsero®, July 2013.

View Bexsero drug record

Further information: Novartis Vaccines

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