Abstract
Background
MenACYW-TT is a new quadrivalent meningococcal conjugate vaccine approved by the US FDA for use in individuals 2 years and older. We present the structured benefit-risk assessment conducted by Sanofi Pasteur in support of the initial biological license application for MenACYW-TT.
Methods
The safety and immunogenicity of MenACYW-TT in subjects ≥ 2 years was evaluated in 5 pivotal randomized, active-controlled clinical trials. Collectively, 4,919 subjects received either a single primary dose (n=4517) or a booster dose (n=402) of MenACYW-TT. A semi-quantitative framework was used to establish favorable and unfavorable effects of MenACYW-TT relative to comparators: MenACWY-CRM in children 2-9 years and adolescents 10-17 years, MenACWY-D in adolescents 10-17 years and adults 18-55 years, and MPSV4 in older adults ≥ 56 years. Benefit outcome measures included vaccine seroresponse and seroprotection (titers ≥ 1:8) at D30 evaluated by serum bactericidal assay using human complement, for each serogroup. Risk outcome measures included rates of solicited injection site and systemic reactions (including grade 3 reactions) within 7 days after vaccination, and rates of serious adverse events within 6 months after vaccination. The differences in rates for MenACWY-TT vs comparator vaccines were calculated along with 95% confidence intervals.
Results
For all benefit criteria, and in all age groups, rate differences favored MenACYW-TT in meningococcal vaccine-naïve individuals. Immune response differences were more pronounced for serogroup C. Differences showed favorable (seroresponse criteria) or comparable (seroprotection criteria) effects for MenACYW-TT in adolescents and adults previously primed with MenACWY-D or MenACWY-CRM. For the risk criteria, rate differences generally showed comparable effects between MenACYW-TT and MenACWY-D or MenACWY-CRM in children, adolescents and adults, while the rate differences for both solicited injection site and systemic reactions favored MPSV4 in older adults. The latter was possibly due to the use of a protein carrier in MenACYW-TT.
Conclusion
The benefit risk-profile of MenACYW-TT in individuals ≥ 2 years is considered favorable relative to comparator licensed vaccines.
Disclosures
David Neveu, MPharm, Sanofi Pasteur (Employee) Marie-Laure Kürzinger, MSc, Sanofi (Employee) Aiying Chen, PhD, Sanofi Pasteur (Employee) Mandeep S. Dhingra, MD, Sanofi Pasteur (Employee)
Immunogenicity and safety of a novel quadrivalent meningococcal conjugate vaccine (MenACWY-CRM) in healthy Korean adolescents and adults
