WHO preferred product characteristics for monoclonal antibodies for passive immunization against respiratory syncytial virus (RSV) disease in infants – Key considerations for global use

Sparrow, Erin; Adetifa, Ifedayo; Chaiyakunapruk, Nathorn; Cherian, Thomas; Fell, Deshayne B.; Graham, Barney S.; Innis, Bruce L.; Kaslow, David C.; Karron, Ruth A.; Nair, Harish; Neuzil, Kathleen M.; Saha, Samir K.; Smith, P. G.; Srikantiah, Padmini; Were, Fred; Zar, Heather J.; Feikin, Daniel R.

doi:10.1016/j.vaccine.2022.02.040

Cited by 24 publications

(23 citation statements)

References 11 publications

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“… 5 The World Health Organization published documents in 2021 that already encouraged the development of preventive interventions for RSV. 9 Palivizumab is currently the most widely used prophylaxis for preventing RSV disease in infants. Two meta-analyses of randomized clinical trials (RCTs) suggested that palivizumab could significantly reduce RSV-related hospitalizations by 51 to 55 per 1000 participants (baseline risk: 98-101 per 1000 participants) compared with placebo.…”

Section: Introductionmentioning

confidence: 99%

Monoclonal Antibody for the Prevention of Respiratory Syncytial Virus in Infants and Children

Sun

Lai

et al. 2023

JAMA Netw Open

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ImportanceRespiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection in children younger than 5 years; effective prevention strategies are urgently needed.ObjectiveTo compare the efficacy and safety of monoclonal antibodies for the prevention of RSV infection in infants and children.Data SourcesIn this systematic review and network meta-analysis, PubMed, Embase, CENTRAL, and ClinicalTrials.gov were searched from database inception to March 2022.Study SelectionRandomized clinical trials that enrolled infants at high risk of RSV infection to receive a monoclonal antibody or placebo were included. Keywords and extensive vocabulary related to monoclonal antibodies, RSV, and randomized clinical trials were searched.Data Extraction and SynthesisThe Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was used. Teams of 2 reviewers independently performed literature screening, data extraction, and risk of bias assessment. The Grading of Recommendations, Assessments, Developments, and Evaluation approach was used to rate the certainty of evidence. A random-effects model network meta-analysis was conducted using a consistency model under the frequentist framework.Main Outcomes and MeasuresThe main outcomes were all-cause mortality, RSV-related hospitalization, RSV-related infection, drug-related adverse events, intensive care unit admission, supplemental oxygen use, and mechanical ventilation use.ResultsFifteen randomized clinical trials involving 18 395 participants were eligible; 14 were synthesized, with 18 042 total participants (median age at study entry, 3.99 months [IQR, 3.25-6.58 months]; median proportion of males, 52.37% [IQR, 50.49%-53.85%]). Compared with placebo, with moderate- to high-certainty evidence, nirsevimab, palivizumab, and motavizumab were associated with significantly reduced RSV-related infections per 1000 participants (nirsevimab: −123 [95% CI, −138 to −100]; palivizumab: −108 [95% CI, −127 to −82]; motavizumab: −136 [95% CI, −146 to −125]) and RSV-related hospitalizations per 1000 participants (nirsevimab: −54 [95% CI, −64 to −38; palivizumab: −39 [95% CI, −48 to −28]; motavizumab: −48 [95% CI, −58 to −33]). With moderate-certainty evidence, both motavizumab and palivizumab were associated with significant reductions in intensive care unit admissions per 1000 participants (−8 [95% CI, −9 to −4] and −5 [95% CI, −7 to 0], respectively) and supplemental oxygen use per 1000 participants (−59 [95% CI, −63 to −54] and −55 [95% CI, −61 to −41], respectively), and nirsevimab was associated with significantly reduced supplemental oxygen use per 1000 participants (−59 [95% CI, −65 to −40]). No significant differences were found in all-cause mortality and drug-related adverse events. Suptavumab did not show any significant benefits for the outcomes of interest.Conclusions and RelevanceIn this study, motavizumab, nirsevimab, and palivizumab were associated with substantial benefits in the prevention of RSV infection, without a significant increase in adverse events compared with placebo. However, more research is needed to confirm the present conclusions, especially for safety and cost-effectiveness.

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Section: Introductionmentioning

confidence: 99%

Monoclonal Antibody for the Prevention of Respiratory Syncytial Virus in Infants and Children

Sun

Lai

et al. 2023

JAMA Netw Open

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“…The WHO recommendations for preferred product characteristics for mAbs seem to be covered in the recent clinical trials phase 3 publication of an almost ready to market extended half-life, 1 , 121 , 162 and we wait to see final product registration and characteristics. Meanwhile, early phase II studies on maternal immunization strategies are ongoing, 124 , 126 , 127 , 130 and although too early to understand if the results will cover WHO recommended PPC, 123 they might be a promising alternative solution to evaluate in the future.…”

Section: Discussionmentioning

confidence: 99%

“… 158–160 In fact, as recently stressed by Li et al, 160 cost-effectiveness of programs with extended half-life mAbs strictly depends on the characteristics of RSV circulation, being appropriate for seasonal interventions, and in order to be cost effective an appropriate price needs to be set similar to vaccine strategies. 160 , 161 Similarly to the recommended PPC for RSV vaccines and maternal immunization, WHO has also issued PPC for mAbs, 162 stating that promising products like a single dose extended half-life mAbs need to have simplified delivery requirements and to be less costly than traditional mAbs, making them potentially suitable for use in all infants and not just those at high-risk. 160 , 161 Moreover, WHO recommends that extended half-life mAbs will target all infants at least for their first 6 months of life, through a one dose regime that could be given from birth.…”

Section: Extended Half-life Mabsmentioning

confidence: 99%

RSV disease in infants and young children: Can we see a brighter future?

Baraldi

Lisi

Costantino

et al. 2022

Human Vaccines & Immunotherapeutics

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Respiratory syncytial virus (RSV) is a highly contagious seasonal virus and the leading cause of Lower Respiratory Tract Infections (LRTI), including pneumonia and bronchiolitis in children. RSV-related LRTI cause approximately 3 million hospitalizations and 120,000 deaths annually among children <5 years of age. The majority of the burden of RSV occurs in previously healthy infants. Only a monoclonal antibody (mAb) has been approved against RSV infections in a restricted group, leaving an urgent unmet need for a large number of children potentially benefiting from preventive measures. Approaches under development include maternal vaccines to protect newborns, extended half-life monoclonal antibodies to provide rapid long-lasting protection, and pediatric vaccines. RSV has been identified as a major global priority but a solution to tackle this unmet need for all children has yet to be implemented. New technologies represent the avenue for effectively addressing the leading-cause of hospitalization in children <1 years old.

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“…In light of this substantial burden, RSV LRTI prevention has been identified as a key priority by the World Health Organization (WHO) for the past 20 years (3)(4)(5). However, despite over 60 years of research, Carbonell-Estrany et al 10.3389/fped.2022.1033125 current preventive measures for RSV disease remain limited to good hygiene and the use of palivizumab, a monoclonal antibody used only for high-risk children, including premature infants (≤35 weeks' gestational age) and those with congenital heart disease and bronchopulmonary dysplasia (6).…”

Section: Introductionmentioning

confidence: 99%

“…Securing access to these interventions at a sustainable cost is often considered the prime concern relating to improving the management of RSV in LMICs ( 8 ). Indeed, WHO has stated that emerging vaccines and monoclonal antibodies should be made available to support optimal use in LMICs ( 9 , 10 ). However, it should be recognised that there are other potential considerations and challenges in LMICs.…”

Section: Introductionmentioning

confidence: 99%

Identifying the research, advocacy, policy and implementation needs for the prevention and management of respiratory syncytial virus lower respiratory tract infection in low- and middle-income countries

et al. 2022

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IntroductionThe high burden of respiratory syncytial virus (RSV) infection in young children disproportionately occurs in low- and middle-income countries (LMICs). The PROUD (Preventing RespiratOry syncytial virUs in unDerdeveloped countries) Taskforce of 24 RSV worldwide experts assessed key needs for RSV prevention in LMICs, including vaccine and newer preventive measures.MethodsA global, survey-based study was undertaken in 2021. An online questionnaire was developed following three meetings of the Taskforce panellists wherein factors related to RSV infection, its prevention and management were identified using iterative questioning. Each factor was scored, by non-panellists interested in RSV, on a scale of zero (very-low-relevance) to 100 (very-high-relevance) within two scenarios: (1) Current and (2) Future expectations for RSV management.ResultsNinety questionnaires were completed: 70 by respondents (71.4% physicians; 27.1% researchers/scientists) from 16 LMICs and 20 from nine high-income (HI) countries (90.0% physicians; 5.0% researchers/scientists), as a reference group. Within LMICs, RSV awareness was perceived to be low, and management was not prioritised. Of the 100 factors scored, those related to improved diagnosis particularly access to affordable point-of-care diagnostics, disease burden data generation, clinical and general education, prompt access to new interventions, and engagement with policymakers/payers were identified of paramount importance. There was a strong need for clinical education and local data generation in the lowest economies, whereas upper-middle income countries were more closely aligned with HI countries in terms of current RSV service provision.ConclusionSeven key actions for improving RSV prevention and management in LMICs are proposed.

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WHO preferred product characteristics for monoclonal antibodies for passive immunization against respiratory syncytial virus (RSV) disease in infants – Key considerations for global use

Cited by 24 publications

References 11 publications

Monoclonal Antibody for the Prevention of Respiratory Syncytial Virus in Infants and Children

Monoclonal Antibody for the Prevention of Respiratory Syncytial Virus in Infants and Children

RSV disease in infants and young children: Can we see a brighter future?

Identifying the research, advocacy, policy and implementation needs for the prevention and management of respiratory syncytial virus lower respiratory tract infection in low- and middle-income countries

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