A Financial and Global Demand Analysis to Inform Decisions for Funding and Clinical Development of Group B Streptococcus Vaccines for Pregnant Women.

BACKGROUND: Despite group B Streptococcus (GBS) being a leading cause of maternal and infant morbidity and mortality, no vaccine is currently available. To inform vaccine developers, countries, and funders, we analyzed the key factors likely to influence the demand for a GBS vaccine and the long-term financial sustainability for a vaccine developer. METHODS: Using population-based forecasting, we estimated the demand for a GBS vaccine; using a discounted cash flow model we estimated the financial viability for a vaccine developer. RESULTS: Demand for this vaccine can be significant if countries adopt policy recommendations for use, in particular, the largest ones, most of which have a burden that justifies use of the vaccine, and if financing for the vaccine is made available either by countries or by funding mechanisms such as Gavi, the Vaccine Alliance. CONCLUSIONS: This analysis suggests the potential for financial and commercial viability for a vaccine developer pursuing the commercialization of a GBS vaccine. Risks exists in relation to the clinical trial design and costs, the level of competition, countries' ability to pay, the administration schedule, and the availability of policies that encourage use of the vaccine. To reduce those risks and ensure equitable access to a GBS vaccine, the role of donors or financers can prove very important, as can a coordinated operational research agenda that aims at clarifying those areas of uncertainty.

Estimating the global demand curve for a leishmaniasis vaccine: A generalisable approach based on global burden of disease estimates.

BACKGROUND: A pressing need exists to develop vaccines for neglected diseases, including leishmaniasis. However, the development of new vaccines is dependent on their value to two key players-vaccine developers and manufacturers who need to have confidence in the global demand in order to commit to research and production; and governments (or other international funders) who need to signal demand based on the potential public health benefits of the vaccine in their local context, as well as its affordability. A detailed global epidemiological analysis is rarely available before a vaccine enters a market due to lack of resources as well as insufficient global data necessary for such an analysis. Our study seeks to bridge this information gap by providing a generalisable approach to estimating the commercial and public health value of a vaccine in development relying primarily on publicly available Global Burden of Disease (GBD) data. This simplified approach is easily replicable and can be used to guide discussions and investments into vaccines and other health technologies where evidence constraints exist. The approach is demonstrated through the estimation of the demand curve for a future leishmaniasis vaccine. METHODOLOGY/PRINCIPAL FINDINGS: We project the ability to pay over the period 2030-2040 for a vaccine preventing cutaneous and visceral leishmaniasis (CL / VL), using an illustrative set of countries which account for most of the global disease burden. First, based on previous work on vaccine demand projections in these countries and CL / VL GBD-reported incidence rates, we project the potential long-term impact of the vaccine on disability-adjusted life years (DALYs) averted as a result of reduced incidence. Then, we apply an economic framework to our estimates to determine vaccine affordability based on the abilities to pay of governments and global funders, leading to estimates of the demand and market size. Based on our estimates, the maximum ability-to-pay of a leishmaniasis vaccine (per course, including delivery costs), given the current estimates of incidence and population at risk, is higher than $5 for 25-30% of the countries considered, with the average value-based maximum price, weighted by quantity demanded, being $5.7-6 [$0.3 - $34.5], and total demand of over 560 million courses. CONCLUSION/SIGNIFICANCE: Our results demonstrate that both the quantity of vaccines estimated to be required by the countries considered as well as their ability-to-pay could make a vaccine for leishmaniasis commercially attractive to potential manufacturers. The methodology used can be equally applied to other technology developments targeting health in developing countries.

Human leishmaniasis vaccines: Use cases, target population and potential global demand.

The development of vaccines against one or all forms of human leishmaniasis remains hampered by a paucity of investment, at least in part resulting from the lack of well-evidenced and agreed estimates of vaccine demand. Starting from the definition of 4 main use cases (prevention of visceral leishmaniasis, prevention of cutaneous leishmaniasis, prevention of post-kala-azar dermal leishmaniasis and treatment of post-kala-azar dermal leishmaniasis), we have estimated the size of each target population, focusing on those endemic countries where incidence levels are sufficiently high to justify decisions to adopt a vaccine. We assumed a dual vaccine delivery strategy, including a wide age-range catch-up campaign before the start of routine immunisation. Vaccine characteristics and delivery parameters reflective of a target product profile and the likely duration of the clinical development effort were considered in forecasting the demand for each of the four indications. Over a period of 10 years, this demand is forecasted to range from 300-830 million doses for a vaccine preventing visceral leishmaniasis and 557-1400 million doses for a vaccine preventing cutaneous leishmaniasis under the different scenarios we simulated. In a scenario with an effective prophylactic visceral leishmaniasis vaccine, demand for use to prevent or treat post-kala-azar dermal leishmaniasis would be more limited (over the 10 years ~160,000 doses for prevention and ~7,000 doses for treatment). Demand would rise to exceed 330,000 doses, however, in the absence of an effective vaccine for visceral leishmaniasis. Because of the sizeable demand and potential for public health impact, a single-indication prophylactic vaccine for visceral or cutaneous leishmaniasis, and even more so a cross-protective prophylactic vaccine could attract the interest of commercial developers. Continuous refinement of these first-of-their kind estimates and confirmation of country willingness and ability to pay will be paramount to inform the decisions of policy makers and developers in relation to a leishmaniasis vaccine. Positive decisions can provide a much-needed contribution towards the achievement of global leishmaniasis control.

Overcoming roadblocks in the development of vaccines for leishmaniasis.

INTRODUCTION: The leishmaniases represent a group of parasitic diseases caused by infection with one of several species of Leishmania parasites. Disease presentation varies because of differences in parasite and host genetics and may be influenced by additional factors such as host nutritional status or co-infection. Studies in experimental models of Leishmania infection, vaccination of companion animals and human epidemiological data suggest that many forms of leishmaniasis could be prevented by vaccination, but no vaccines are currently available for human use. AREAS COVERED: We describe some of the existing roadblocks to the development and implementation of an effective leishmaniasis vaccine, based on a review of recent literature found on PubMed, BioRxiv and MedRxiv. In addition to discussing scientific unknowns that hinder vaccine candidate identification and selection, we explore gaps in knowledge regarding the commercial and public health value propositions underpinning vaccine development and provide a route map for future research and advocacy. EXPERT OPINION: Despite significant progress, leishmaniasis vaccine development remains hindered by significant gaps in understanding that span the vaccine development pipeline. Increased coordination and adoption of a more holistic view to vaccine development will be required to ensure more rapid progress in the years ahead.

Shaping markets to benefit global health - A 15-year history and lessons learned from the pentavalent vaccine market.

Market shaping for health products used in lower-income countries strives to benefit public health. As a funder of vaccines, Gavi, The Vaccine Alliance (Gavi) has goals for its market shaping efforts, achieved through a strategy developed and implemented by the Gavi Secretariat, UNICEF, the World Health Organization (WHO) and the Bill & Melinda Gates Foundation (BMGF). A case-study of Gavi's fifteen-year engagement with a vaccine against diphtheria, tetanus, pertussis, hepatitis B and haemophilus influenzae type b (pentavalent) provides evidence of the benefits and potential risks of trying to influence markets. During 2001-18, Gavi disbursed US$3.5 billion to support use of 50 million pentavalent doses annually before 2005, increasing to ∼300 million doses annually by 2016. During this time, eight manufacturers invested in vaccine development and manufacturing and the first two manufacturers have subsequently ceased production. Following its strategy, Gavi implemented coordinated market interventions including technical assistance to manufacturers, improving market information transparency, risk-sharing agreements and innovative procurement aiming to stimulate and capitalize on a competitive market. In 2018 supply allows ∼80 million children per year to be immunised, a sixteen-fold increase from 2005, with vaccine-related costs per child for donors and countries of one-quarter the 2005 level. Lessons learned include the importance of frameworks and strategies; the need to adjust interventions with changing conditions; the important role of manufacturers; and the potentially powerful effects of interconnected markets. This case study is limited by its focus on a single health product in a specific market, however the lessons can inform other market shaping efforts when taken in context. While countries and children have improved vaccine access, risks of financial sustainability and continued manufacturer investment in Gavi vaccine markets are being monitored. Gavi should continue implementing a market shaping strategy, adjust with market conditions and expect and measure unintended consequences.