Neveu David, Mallett Moore Tamala, Zambrano Betzana, Chen Aiying, Kürzinger Marie-Laure, Marcelon Lydie, Singh Dhingra Mandeep
Global Pharmacovigilance, Sanofi, Swiftwater, PA, USA.
Global Clinical Development Strategy, Sanofi, Montevideo, Uruguay.
Infect Dis Ther. 2023 Oct;12(10):2367-2386. doi: 10.1007/s40121-023-00864-4. Epub 2023 Sep 27.
A favorable benefit-risk balance is required to support licensure of biologics, in keeping with regulatory agencies' evolving recommendations, including the United States Food and Drugs Administration. We present a structured semi-quantitative benefit-risk analysis of MenACYW-TT, a quadrivalent meningococcal conjugate vaccine against Neisseria meningitidis serogroups, A, C, W and Y versus licensed comparators in individuals aged ≥ 12 months.
We used data from six MenACYW-TT clinical trials, stratified by age group, versus licensed vaccines: toddlers (12-23 months; Nimenrix [MCV4-TT]), children (2-9 years; Menveo [MCV4-CRM]), adolescents (10-17 years; MCV4-CRM or Menactra [MCV4-DT]), adults (18-55 years; MCV4-DT) and older adults (≥ 56 years; Menomune-A/C/Y/W-135 [MPSV4]). Eight benefit (seroresponse and seroprotection for A, C, W and Y) and five risk outcomes (any and grade 3 solicited injection site and systemic reactions, and serious adverse events) were measured at Day 30 after initial vaccination. Analyses were conducted by baseline vaccination status (meningococcal vaccine-naïve or vaccine-primed).
MenACYW-TT showed favorable seroresponse and seroprotection among vaccine-naïve participants aged ≥ 2 years, against all serogroups, compared with MCV4-CRM, MCV4-DT and MPSV4. In vaccine-naïve toddlers, there was a favorable effect for serogroup C, but no difference between MenACYW-TT and MCV4-TT for serogroups A, Y and W. A favorable effect for MenACYW-TT against serogroup C was observed in all vaccine-naïve and combined vaccine-naïve and MenC conjugate vaccine-primed groups. For all risk criteria, there were no differences between MenACYW-TT and MCV4s in toddlers, children, adolescents and adults. Results for solicited injection site and systemic reactions favored MPSV4 in older adults.
The benefit-risk profile for MenACYW-TT showed favorable seroresponse and seroprotection in individuals aged ≥ 2 years and no difference in risk criteria between MenACYW-TT and MCV4s. MenACYW-TT may provide an alternative to the standard-of-care for meningococcal disease prevention in those aged ≥ 12 months.
为支持生物制品的许可，需要有良好的效益风险平衡，这与监管机构不断演变的建议一致，包括美国食品药品监督管理局的建议。我们对ACYW-TT四价脑膜炎球菌结合疫苗进行了结构化的半定量效益风险分析，该疫苗用于预防≥12月龄个体中A、C、W和Y血清群的脑膜炎奈瑟菌，与已获许可的对照疫苗进行比较。
我们使用了六项ACYW-TT临床试验的数据，按年龄组分层，与已获许可的疫苗进行比较：幼儿（12 - 23个月；Nimenrix [MCV4-TT]）、儿童（2 - 9岁；Menveo [MCV4-CRM]）、青少年（10 - 17岁；MCV4-CRM或Menactra [MCV4-DT]）、成人（18 - 55岁；MCV4-DT）和老年人（≥56岁；Menomune-A/C/Y/W-135 [MPSV4]）。在初次接种疫苗后第30天测量八项效益指标（A、C、W和Y血清群的血清反应和血清保护）和五项风险指标（任何和3级的接种部位和全身反应，以及严重不良事件）。分析按基线疫苗接种状态（未接种过脑膜炎球菌疫苗或已接种过疫苗）进行。
与MCV4-CRM、MCV4-DT和MPSV4相比，ACYW-TT在≥2岁未接种过疫苗的参与者中对所有血清群均显示出良好的血清反应和血清保护。在未接种过疫苗的幼儿中，对C血清群有良好效果，但ACYW-TT与MCV4-TT在A、Y和W血清群方面无差异。在所有未接种过疫苗以及未接种过疫苗与MenC结合疫苗初免的联合组中，均观察到ACYW-TT对C血清群有良好效果。对于所有风险标准，ACYW-TT与MCV4在幼儿、儿童、青少年和成人中无差异。在老年人中，接种部位和全身反应的结果显示MPSV4更优。
ACYW-TT的效益风险特征显示，在≥2岁个体中具有良好的血清反应和血清保护，且ACYW-TT与MCV4在风险标准方面无差异。ACYW-TT可能为≥12月龄个体预防脑膜炎球菌疾病的标准治疗方法提供一种替代方案。
