Respiratory syncytial virus (RSV) is a leading cause of hospitalization in infants and young children because of lower respiratory tract illness, encompassing bronchiolitis and pneumonia. RSV causes a potentially life-threatening disease that kills >100 000 children each year, disproportionally concentrated (99%) in low- and middle-income countries (LMICs),1 whereby RSV’s attributable mortality might even be underreported.2 RSV prevention is a major unmet need in these settings; however, the only commercially available preventive tool, until recently, was the monoclonal antibody (mAb) palivizumab (Synagis, Sobi), requiring multiple doses and with costs >$5000 per child, compromising its wide use. Unsurprisingly, 99% of sales of this product are concentrated circumscribed to high-income countries.3
A great level of excitement exists among pediatricians and stakeholders working toward the reduction of child mortality because 2 new tools have emerged: a maternal vaccine and an optimized long-lasting mAb, both recently approved for the prevention of RSV disease. Access to such preventive products is paramount to meaningfully impact RSV burden, reducing mortality and pressure on health systems. Here, we highlight the great potential of the new mAb and advocate for a broader deployment in LMICs, where the disease and mortality burden are highest.
Nirsevimab (Beyfortus, AstraZeneca/Sanofi), the new anti-RSV mAb, has shown high efficacy in infants with 1 shot (50 mg <5 kg; 100 mg >5 kg), particularly when delivered at the beginning of the RSV season. In clinical trials,4 efficacy remains high (78.6% [95% CI, 48.8–91.0]) up to 150 days after the injection against very severe RSV-associated lower respiratory tract infection (defined as requiring hospitalization and treatment with supplemental oxygen or intravenous fluids).
This new product has successfully met many of the WHO-preferred product characteristics,2 including the extended half-life that renders 1 injection possible: an enormous advantage compared with its predecessor (which required 5 monthly injections), especially where monthly access to infants at risk is not possible.
In Spain, since October 2023, nirsevimab has been deployed as a prevention tool within the universal health coverage scheme. It has shown high effectiveness in preventing severe RSV infection in infants, mimicking the results of the clinical trials in real life. As first reported from regions like Galicia,5 the uptake has been >90%, and RSV-related hospitalizations have decreased between 70% to 90%, compared with pre-COVID-19 seasons (whereas no significant reductions in RSV circulation were documented in the same period). In other Spanish regions, effectiveness in preventing hospitalization ranged between 69% and 96%.6
We believe that key success factors enabling such a level of implementation have included: early engagement with the pharmaceutical company, leading to adequate accessibility to the product; population-wide access through public, universal health care whereby the regional governments pay for the product; a proactive campaign; the inclusion of all susceptible infants born during the RSV season from October 1, 2023, until March 31, 20245 ; and active catchment of infants born from April 2023 to September 30, 2023, including awareness campaigns and use of phone reminders.
However, as of today, this game-changing tool, similarly to most of the mAbs currently in the market, suffers from severe market shortcomings, hindering its broader uptake. Inequities exist both between and within high-income countries, and, particularly, in LMICs where the virus causes the greatest mortality. In such settings, perspectives for its future implementation remain utopic.
At the moment, only 1 source exists for the new mAb nirsevimab. In Spain, during this first season of implementation, the negotiated price reached €209 per shot, 1 of the lowest reported together with the price made available for Chile ($200), the first country in Latin America to launch a prevention campaign with the mAb. In other markets, prices ranging between $395 and $495 per dose have been reported. In addition, production is limited, and demand has largely exceeded supply, leading to shortages and rationing in many countries. For example, in the United States, in the context of limited supply during this 2023–2024 RSV season, the Centers for Disease Control and Prevention recommended prioritizing available nirsevimab for infants at the highest risk for severe RSV disease (infants <6 months and infants with underlying conditions).
At least 3 more mAbs are in the pathway2 that could bring about potential advantages for resource-limited settings, including a low price, such as the product under development by the Bill and Melinda Gates Medical Research Institute. Although timelines are uncertain, 1 of the new candidates (clesrovimab, Merck) is already in phase III clinical trials and could be approved by 2025.
Very importantly, prices would be major determinants of the cost-effectiveness of these emerging products, and, in turn, of their adoption in LMICs.2 Likewise, the requirements in the Vaccine’s Alliance’s investment case should be met to enable support for scaled-up use in the countries they serve. Furthermore, other promising mAbs are in the pipeline that could address other unmet needs in major diseases affecting children in LMICs, such as malaria or HIV; enabling access to mAbs for RSV could be a trailblazer.
A strategic collaborative action plan needs to be developed with all stakeholders, public and private, including LMICs’ governments, caregivers and communities, donors, global health agencies, developers, and biopharmaceutical manufacturing companies. This will enable prompt addressing of the outstanding obstacles to equitable access for such products in LMICs, including lack of affordability, insufficient and concentrated production, lack of global procurement systems, unclear regulatory and country’s introduction, and uptake pathways.
A number of tools are available to global and national stakeholders to accelerate access to innovative lifesaving products, as described in Unitaid’s Access Toolbox and, in particular for monoclonal antibodies, as discussed in multistakeholder consultation Novel Business Models for Accessible mAbs in LMICs,7 including complementary actions such as: (1) addressing intellectual property, broad licensing, and technology transfer for current and pipeline products; (2) increasing supply capacity and competition to reduce prices; (3) supporting the development of alternative products that can meet the WHO-preferred product characteristics, responding to public health–oriented access terms; (4) optimizing production and increasing visibility in demand to decrease cost; (5) improving availability of funding to de-risk manufacturers’ investments to anticipate scale-up production; and (6) supporting the process to enable authorizations for use at the country level and render products eligible for donor supply.
Delivery and implementation for such new products, and their scaled use, will pose new and significant challenges that warrant prompt attention as well. There is a need to work with national stakeholders and communities all along the way to ensure adoption responds to their priorities, raising awareness, and supporting early catalytic introduction to determine optimal delivery and implementation mechanisms.
Preventing and managing respiratory infections in early childhood is complex and needs to consider the myriad of factors—societal, cultural, and biomedical—that can influence the effect of interventions and end-user decisions. However, access to the optimized preventive tools, including the new and emerging mAbs, is a necessary element to unlock the pathway for LMICs and should be urgently addressed given the high mortality associated with this virus among the most vulnerable. Real-life experience in Spain, as described here, and that of other high-income countries reporting similar results, should allow us all to dream high and aspire to a similar impact translated to those areas of the world that concentrate the highest burden and, thus, the higher needs against this preventable virus for which no treatment exists.
Ms Pérez-Casas and Dr Tagarro conceptualized the article, undertook the writing and the literature search, and reviewed the final manuscript; Drs Bassat and Rojo conceptualized the article and reviewed and revised the final manuscript; and all authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.
FUNDING: No external funding.
CONFLICT OF INTEREST DISCLOSURES: Dr Rojo participated in Abriysvo (Pfizer) and Beyfortus (Astra-Zeneca/Sanofi)’s clinical trials as principal investigator at his hospital. The other authors have indicated they have no potential conflicts of interest to disclose.
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