The 2025 Neglected Disease R&D Pipeline review: Time to close the gaps

Amid a climate of political uncertainty and spreading infectious diseases, this report takes stock of the health of the product pipeline for neglected diseases (ND). With global funding more limited than ever, smart choices are needed. We examine a decade of the ND pipeline to help funders, policymakers, and advocates set the right priorities and maximise the impact of the money they invest in global health.

This report builds on our previous work on the Impact of Global Health R&D, which revealed that the past 20 years of investment in ND R&D will save 40.7 million lives, avert 2.83 billion DALYs and generate a net benefit of $49.7 trillion to society by 2040 – implying that every dollar invested in neglected disease R&D generates a return of $405.

As of February 2025, the ND pipeline boasts 799 active candidates.¹ This represents a significant (65%) increase since we first began monitoring the pipeline in 2015, even after controlling for additional diseases added to our scope. However, all the growth occurred between 2015 and 2023, and the number of products has stagnated since then. When compared to our 2023 pipeline, the only growth is a result of changes in methodology.²

Figure 1: Growth of the pipeline 2015-2025

A like-for-like comparison with 2023 shows the 2025 pipeline shrank slightly, by 2%, after accounting for an artefactual increase in diagnostics, caused by a change in how we count them.² The period between 2023 and 2025 saw a decline in vaccines (down 15%, 42 candidates) overshadowing growth in drugs (up 17%, 35 candidates) and vector control products (up 56%, 9 candidates). This broadly aligns with the long-term trends in R&D funding, painting a picture of uneven progress across the pipeline and suggesting that some R&D gaps may be addressed sooner than others.

Figure 2: 2025 pipeline overview

Are there now enough promising candidates in clinical development to satisfy the wide range of unmet needs for NDs, especially given candidates’ inevitable attrition?

Across all product types, 64% of the clinical stage candidates in the 2023 pipeline are still active in 2025. Most of this apparent attrition is a lack of R&D activity since 1 January 2022, with only 17% of 2023 candidates deliberately leaving the pipeline due to efficacy shortfalls.

Cuts to several countries’ ODA budgets, slashed funding to US NIH, and dismantlement of USAID and others are likely to exacerbate the uneven progress across product types and diseases and stall the necessary replenishment of the pipeline.

Figure 3: Pipeline by product type and granular R&D stage³

^{1 The ‘active’ pipeline is restricted to candidates with evidence of ongoing R&D activity since 1 January 2022. This includes peer-reviewed articles, press releases, clinical trials (commenced, ongoing or completed), and developer’s portfolio listings between 1 January 2022 and 28 February 2025. Candidates were excluded if no evidence of activity was found or if the candidate had been intentionally abandoned by the developer (removed from portfolio, failed to meet safety or efficacy).}

^{2 For the 2025 update, we disaggregated diagnostic tests that were previously grouped by similar technologies (resulting in 15 additional candidates), leveraged FIND’s DxConnect test directory after its launch in 2022 (40 additional candidates) and added yaws to our scope (3 additional candidates).}

^{3 Biologics was added to our scope in the 2023 pipeline review.}

Remaining funders need to strike a balance between advancing the maturing pipeline to the finish line and replenishing it with new candidates. To manage both tasks, with a smaller pool of money, funders will need to explore efficiencies at both the candidate and portfolio levels.

Platform trials make R&D quicker and cheaper

One key strategy for doing more with less is taking a different approach to clinical trials. Platform trials are one example: these innovative randomised controlled trials are designed to simultaneously evaluate multiple interventions within the same trial structure, with a single, shared, control group. Platform trials are efficient and flexible, allowing modification of the ongoing trial at preplanned timepoints after reviewing accumulated data. Existing trial arms can be dropped if an intervention is shown to be ineffective, or new interventions can be added as amendments rather than starting a new trial, saving time and money.

While platform trials are complex and have longer setup times, reusable master protocols and infrastructure along with the ability to test multiple candidates simultaneously reduces trial cost by 12-15% and cycle time by 13-18% compared to traditional clinical trials. An illustrative example is the ongoing PLATINUM trial, which is simultaneously testing three novel anti-malarial agents as monotherapies and/or combination therapies.

A major barrier to wider adoption of platform trials is the need to secure the agreement of multiple developers, some of whom may resist the loss of control associated with a shared trial. The product development partnership (PDP) R&D model, where a single funder backs a portfolio of candidates, lends itself to this structure and brings economies of scale to product development. The real challenge is coordination of developers and funders, who must openly share their candidates to enable collaboration and pooling of resources. A cultural shift is needed to incentivise more developers to undertake this approach, so that champions of an unsuccessful candidate are rewarded (or at least not punished) for failing fast rather than trying to ‘p-hack’ their way to non-inferiority. The value proposition offered by the platform trial – derisking R&D programs and reducing cost and cycle time – can help in selling the necessary cultural shift. We can also learn from oncology, which has been utilising this approach for more than a decade. While platform trials are ideal, they are not always possible. In their absence, we need to advocate for harmonisation of trial design so different trials for the same indication are at least more easily compared.    

Common trial standards to accelerate pipeline progress and enable comparison

By supporting the development of standardised reference materials, standard assays, infection models (animal and controlled human infection models) and correlates of protection, funders can help multiple areas of the pipeline at once and even provide spillover benefits to entirely different product types. One such example is the WHO recommendation of typhoid conjugate vaccines based on immunogenicity data from controlled human infections models. Standardisation, which can enable comparison and availability of these types of models for all NDs, can also aid in clinical trial harmonisation.

Reuse existing R&D infrastructure to avoid reinventing the wheel

Another way to make funding go further is to take advantage of spillovers from elsewhere in the pipeline. Leveraging the existing infrastructure, technology platforms, and delivery systems developed for one product can accelerate the discovery, development, and production of candidates across multiple disease areas. This approach would also make commonplace the repurposing of infrastructure built for ineffective products for use by others, avoiding the need to build things twice. It also enhances efficiency and cost-effectiveness by reducing the resources required for preclinical and clinical development. However, not all diseases have the same geographic spread so leveraging clinical trial capacity, particularly trial sites, across different diseases may not always be possible.

Applying existing technologies to other conditions can also help streamline regulatory approval. The rapid adaptation during the COVID pandemic of mRNA technology built on decades of prior research demonstrated how platform technologies can facilitate rapid vaccine development. This technology is now being applied to many other diseases, including malaria and TB with candidates in clinical development and a promising preclinical candidate for rotavirus.

Lessons learned, technologies and established infrastructure for vaccine development are being used to support the discovery, development and deployment of biologics ⁴ such as monoclonal antibodies (mAbs). This is especially critical in low- and middle-income countries, where progress in the prevention and control of certain high-burden diseases, like malaria, has stalled. In recent years, mAbs have shown potential to address these gaps either as standalone therapies or in combination with other products. These include research by IAVI and Scripps Research exploring vaccination strategies that stimulate production of broadly neutralising antibodies, thought to provide long-lasting immunity for HIV. Increasingly, researchers are exploring combination platform technologies to boost an individual candidate’s efficacy and durability. For instance, the use of viral vector platforms to deliver genes encoding broadly neutralizing antibodies for HIV prevention, aiming to achieve sustained antibody expression from a single dose. These hybrid approaches hold promise for advancing candidates through the pipeline and improving access in resource-limited settings.

The HIV vaccine landscape also demonstrates the need to balance advancing the late-stage pipeline with replenishment of the early-stage pipeline. All Phase III HIV candidates have now fallen short, leaving a relatively immature pipeline with 78% of candidates in Phase I and 20% in preclinical development. Fortunately, years of sustained R&D investment in HIV helped maintain this early-stage pipeline – the most diverse vaccine portfolio amongst NDs –  so we’re not starting from scratch. But this isn’t the case for all diseases. The leading TB vaccine candidate, M72/AS01E, is running ahead of schedule in Phase III trials but, with only 50% efficacy and a focus on adult populations, it may not meet all our needs. Other late-stage TB candidates, VPM1002 and Immunovac, appear unlikely to fill the gaps left by M72, as Indian regulatory authorities have requested more safety data for both. If these candidates fail, the already slow TB vaccine pipeline will face further delays as the majority of remaining candidates are still in preclinical development (17). There is a clear lesson here: sustained early-stage investment is critical, and the HIV vaccine field, despite its setbacks, offers a valuable example of how to build and sustain vaccine R&D resilience.

Accelerator-style partnerships improve coordination and access

Accelerator-type partnerships, like the Tuberculosis Drug Accelerator and those launched for the COVID-19 pandemic, could be leveraged further for neglected diseases. By creating structured frameworks for collaboration, these partnerships could coordinate end-to-end development accelerating R&D, production, and access to essential products across the wide spectrum of NDs. They could also coordinate more effectively between the many stakeholders involved and reduce redundant investment. As a starting point, ND R&D accelerators could be established with the intent of delivering clinical trial-ready candidates to replenish and revitalise the preclinical pipeline, bringing together academia, industry, PDPs and funders. They could also bridge the gap between approval and access which, like late-stage trials, is another ‘valley of death’ for many products. These accelerators must be more than talking shops, with clear aims, objectives and monitoring and evaluation frameworks.

^{4 The biologics category refers to investigational biological agents and therapeutic vaccines specifically intended to prevent or treat infection, including broadly neutralising monoclonal antibodies (bNAbs); polyclonal antibodies; and other bio therapeutics such as peptide-, DNA- and RNA-based synthetic molecules.}

With funding being so stretched, what smarter choices can we make? Tools like the recent WHO investment case for TB vaccines allow us to assess the impact of a product to ensure we are developing the right products for the right indications. Modelling impact on mortality, morbidity and incidence can help funders identify which products will result in the greatest benefit and help capture the potential benefits of eliminating smaller diseases like mycetoma. Funders typically conduct these value assessments only for their own portfolios, but a collection of value propositions for different product types across the ND landscape by bodies like the WHO or an ND accelerator could make them broadly accessible and help to make the case for funding ND R&D to organisations outside the usual list of contributors.

There are areas of the product landscape where we already know that a breakthrough technology would close product gaps and potentially revolutionise the landscape.

Some of these breakthrough technologies won’t be realised for several years. What can funders invest in now to push candidates across the finish line?

The PDP model has delivered many existing breakthrough products

Products to prevent, treat and diagnose NDs must meet the needs of those most affected. For over 20 years, PDPs have championed the development of products that close R&D gaps and put people first.

Among the 69 PDP-supported products across all diseases, 73% have achieved WHO prequalification, 32 of them in the last five years. Some recent approvals are the ‘first of their kind’: DNDi’s partnership with Swiss TPH and Sanofi delivered fexinidazole, the first all-oral cure for human African trypanosomiasis, eliminating the need for hospitalisation; Vectron T500, supported by IVCC, utilises a new active ingredient – broflanilide – for indoor residual spraying against mosquitoes and provides prolonged control of pyrethroid-resistant malaria vectors; the dapivirine vaginal ring is the world’s only approved microbicide, a breakthrough in discreet long-acting HIV pre-exposure prophylactic technology, supported by the International Partnership for Microbicides.

PDPs play a pivotal role in key disease-product areas of the pipeline, where they support 40% or more of the candidates for Buruli ulcer drugs and diagnostics, helminth vaccines, HIV microbicides, kinetoplastid biologics and drugs, leprosy vaccines, malaria drugs, and TB biologics. Candidates in PDPs’ late-stage pipeline, if approved, could close additional product gaps: Emodepside, supported by DNDi, could be the first macrofilaricidal – adult worm killing – drug to treat onchocerciasis; RV3-BB, supported by PATH, could be the first birth-dose vaccine for rotavirus, making vaccination possible before six weeks of age.

Figure 4: 2025 PDP-supported pipeline

Building access into the development process 

Approved products can’t reduce burden if patients can’t get them. Access-oriented business models, where developers consider market access earlier in a product’s life-cycle, can help bridge the gap between product launch and implementation, as we’ve seen with the long-acting injectable lenacapavir for HIV prevention. Non-exclusive, royalty-free voluntary licensing agreements have been set up ahead of lenacapavir’s regulatory approval, making low-cost generic formulations available to LMICs soon afterwards. The Medicines Patent Pool (MPP) facilitates similar agreements to ensure access to essential medicines at a low-cost and reduce the delay before generics become available. With the MPP currently focused on only HIV, TB and hepatitis C, its model should be expanded to secure access to affordable medicines for more NDs, possibly as part of the ND accelerator we call for above.

Funders also need to partner with developers to facilitate access to approved products by ensuring endemic regions have timely access to distribution, or, ideally, local manufacturing. The technology transfer agreements signed for the RTS,S/AS01 malaria vaccine between GSK, Bharat Biotech and PATH, for example, are expected to increase supply and reduce prices. This kind of engagement with large-scale manufacturers during late-stage development is vital to securing production and supply prior to WHO recommendation and approval from programs like Gavi. In a perfect world, facilities used to supply doses for late-stage trials would pivot to larger scale manufacture, serving as a bridge between trials and global distribution. 

 A lack of commercial incentives will remain for low burden diseases, and even for higher burden conditions whose sufferers can’t afford medications. Solely focusing on local manufacturing to help fill this gap fails to address the underlying market failure that will prevent them being invented in the first place. We must also reduce dependency on pharmaceutical companies donating products post-approval, in favour of a sustainable local manufacturing industry for products for which there will be a long-term demand. This requires a shift towards country-led investment where domestic investment in scientific skills both fosters local R&D and also spills over into capacity for manufacturing. Even with the assistance of an ND accelerator and others, building domestic research and manufacturing capacity in LMICs will take time. In the meantime, we need to balance this effort with funding that recognises the missing markets for neglected disease products.

Translating approval into access

Just over a quarter of all approved products since 1999 through to 2025 (270, 28%) are WHO prequalified, offering assurance to member states and UN procurement agencies that they are suitable for use in national programs. Rates of prequalification are significantly higher for vaccines (72%) and drugs (46%). Of the 812 approved diagnostics, though, just 19% are WHO prequalified, reflecting the limited scope of the diagnostics prequalification process – which covers just HIV, hepatitis B, hepatitis C, malaria, cholera and TB. Even medicines that are prequalified, included in the WHO Essential Medicines List or recommended by the WHO often won’t reach resource-constrained countries quickly. For example, since 2018, WHO- recommended typhoid conjugate vaccines have only been introduced in just six endemic countries. Practical access plans should be integrated early in the R&D process, and the WHO could consider requiring developers to include access plans in their submissions, moving beyond reliance on UN procurement agencies. Equally important is early engagement with country-level stakeholders to address local barriers well before approval and/or prequalification – another area which could be facilitated by an ND accelerator. Without these steps, the impact of WHO prequalification will remain limited.

The diagnostics pipeline lacks diversity despite large numbers

For products to deliver genuine impact, they need to provide a meaningful improvement to the existing standard of care. Diagnostics comprise 83% of the ND product landscape but many of the approved products and candidates are ‘me too’ products: iterations of existing core technologies, utilising common targets and with the same intended use cases, resulting in a homogenous portfolio.

Developing ND diagnostics poses multiple complex challenges . They need to be accurate, reliable and affordable, especially for LMICs, as high costs can limit uptake. A lack of regulatory alignment means developers must navigate varying requirements across countries, adding to the cost of ensuring a consistent supply chain, particularly in remote areas. Often, the necessary financial incentive for large companies to invest in ND diagnostics is simply not there, particularly since their incremental impact – which requires treatment following diagnosis – can be hard to demonstrate.

Figure 5: 2025 pipeline by WHO prequalification

Given these challenges, smaller biotechnology firms typically take the lead in diagnostic development. Their agility allows them to innovate rapidly and adapt to emerging needs, focusing on niche markets that larger companies often overlook. These small biotechs frequently collaborate with academic institutions, non-profits, and public sector organisations, leveraging grants and partnerships to fund their research. Their willingness to take risks on unproven technologies is crucial for advancing new solutions in areas where traditional market forces are insufficient. As global health diagnostics continue to evolve, enabling these small biotech companies through risk sharing, reliable funding opportunities and predictable regulation will be essential to improving access to life-saving tools.

Adapting to reduced public funding means every dollar counts more

With increasing questions about the value of official development assistance (ODA) to LMICs, a number of donor governments have already scaled back their commitments. The UK and several European countries have significantly reduced their ODA budgets, and the United States government – until recently, the largest donor to global health  – has also implemented deep cuts to foreign aid. This collective retreat increases pressure on the limited pool of remaining resources and could potentially stall progress.

Since 2007, US agencies’ funding has reached over 43 LMICs, contributing to the strengthening of local R&D and manufacturing capacities. This means that reducing or suspending research funding will not only impact the current pipeline but also opportunities for future innovation. Cuts to the US NIH, the largest global funder of basic research in neglected diseases, will hinder the development of new products and weaken the foundational science needed to guide innovation. The kinds of basic research traditionally backed by the NIH are crucial for shaping target product profiles, designing clinical trials, and developing tools to assess product efficacy.

Figure 6: 2025 United States Government-supported pipeline

How can PDPs remain viable with reduced public funding and industry contributions?

ODA cuts pose a significant risk to the sustainability of product development partnerships (PDPs), a model that has been instrumental in advancing neglected disease R&D. Since 2019, PDPs have supported ten different approved products , including four drugs, three vaccines and three chemical vector control products. With significant reductions in public funding, which has historically been responsible for providing almost half of the global support for PDPs, and the retreat of industry in the global health landscape, continuing to rely on a small number of unstable funding streams no longer seems viable. The PDP model is vulnerable as these two key partners – public funders and industry – continue their retreat. Much of the support PDPs currently receive from industry is “in kind” contributions of expertise to conduct R&D. But as industry are now outsourcing many of these such as discovery and CMC (chemistry, manufacturing and controls), their contributions to PDPs are getting smaller, necessitating PDPs to develop these skills in house.

Local ownership can help R&D match local needs

One promising development in the face of funding cuts is a move towards greater local ownership and regional coordination, particularly within and between LMICs.

This shift will enable governments and agencies to work collaboratively, minimising inefficiencies by making earlier, evidence-based decisions on which candidates to advance, as well as preventing fragmented and overlapping efforts. This would allow more work to be done in lower cost environments, and enable LMICs to capture more of the economic and scientific benefits from conducting R&D domestically. For instance, in response to the changes in high-income country funding, Africa CDC is working to unify R&D efforts to ensure products that meet local needs advance to licensure. Central to this effort is the establishment of a continental health R&D coordination and governance framework. This framework will help countries define their priorities and develop evidence-based health policies.

Using the impact of global health R&D to make the case for new types of funding

Our research has shown that investing in global health R&D delivers a massive return on investment – $405 in societal value for every $1 invested. It also strengthens national economies by generating jobs, creating value in intellectual property, and catalysing industry investment. While we continue to champion the importance of global health R&D investments to traditional funders, we are at a critical juncture where we need to tap into new avenues to advance the ND pipeline.

An example of this being explored on the African continent is tapping into sovereign wealth funds and expanding the role of Development Financial Institutions (DFIs), like the World Bank, African Export-Import Bank (Afreximbank) and the African Development Bank. Afreximbank is supporting Africa CDC with a $2 billion facility through the Africa Health Security Investment Plan to advance regional manufacturing goals, focusing on the African Pooled Procurement Mechanism (APPM) and the Platform for Harmonized African Health Products Manufacturing (PHAHM). Through its 2022–2030 strategy, the African Development Bank is investing $3 billion in Africa’s pharmaceutical industry and has launched the African Pharmaceutical Technology Foundation to boost local manufacturing and improve access to essential technologies. Innovative strategies are also being explored to boost domestic investment in health, including ‘solidarity levies’ – taxes on goods and services with their revenue directed to health spending – and leveraging diaspora remittances to support health spending. Ultimately, success will depend on sustained political will, regional cooperation, and accountability.

With reduced public funding, public-private partnerships offer significant potential to boost investments to ensure that products reach people in need. However, private sector participation is often constrained by the risks and by gaps in the data they need to assess market size and areas of greatest potential impact. These are factors that are particularly relevant to monoclonal antibodies, which remain largely inaccessible in LMICs. While mAbs are often viewed as too expensive for LMIC health systems, this overlooks their long-term potential.

Concessional finance from public sources to serve as first-loss capital can make these kinds of investments more attractive to private investors, especially in areas like neglected diseases that are often viewed as high-risk or lacking immediate profitability. These blended financing models, combining private and public sector capital, with risks sharing, allowing governments to leverage private capital to reduce financial burden on public resources and offering private investors some protection against risks.  

We must also rethink funder engagement strategies, including re-evaluating the role of ND R&D funders and how to leverage different sources of capital by matching potential funders’ interests and risk tolerance with the right collaborators and at the right point in the R&D lifecycle. Improved coordination between different funders, each with varying levels of risk tolerance, could create a smoother, more efficient transition between stages of R&D, helping to avoid the notorious late-stage ‘valley of death’ by ensuring the right support is in place at each Phase.

Engagement in pre-competitive consortia, like the Innovative Medicines Initiative in Europe and the Accelerating Medicines Partnership in the US, further demonstrate how public and private sectors can jointly address development bottlenecks by sharing expertise, resources, risks, and costs, making investment in neglected disease R&D more attractive to funders who have traditionally avoided it.

Visual summary: 10 ways to fill the gap more quickly

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Spending on global health is spending on regional security

COVID-19 and Mpox have made it clear that infectious diseases are not confined to LMICs; high-income countries are increasingly vulnerable. Climate change and globalisation are expanding the range of diseases, leading to the geographic spread of Chagas, dengue, Zika, and chikungunya, while the recent resurgence of locally transmitted malaria in the US highlights the thin line between global and domestic health security. Since today’s remote health threats can quickly become tomorrow’s global crises, we need to make it clear that strengthening R&D ecosystems worldwide is a matter of local self-interest for everyone. Positioning global health R&D as a strategic investment in security, economic stability, and resilience can attract broader political and financial backing.

This broader perspective invites non-traditional stakeholders, such as defence and foreign affairs ministries, into the conversation, integrating global health innovation into wider discussions on national security and foreign policy.

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