There is a global lack of preparedness and reactive responses when confronted with emerging epidemic threats, a concerning lack of investment in the R&D vaccine and therapeutics pipeline, and signs of waning focus on pandemic preparedness, according to a new report by the International Pandemic Preparedness Secretariat (IPPS).

The IPPS launched its third annual report on the 100 Days Mission (100DM) for pandemic preparedness at the Accademia dei Lincei in Rome on Wednesday.

The report assesses how much progress has been made toward ensuring the global availability of diagnostics, therapeutics, and vaccines (DTVs) within the first 100 days of a pandemic threat. It also evaluates progress toward 100 Days Mission target of two antiviral therapies for each high-risk viral family, ready for Phase II/III clinical trials by 2026.

“In 2021, a group of G7 scientific advisors and experts came together to set out the recommendations that would form the basis of the 100DM,” explained 100DM outgoing chair Sir Patrick Vallance in the report’s introduction.

“Since then, the world has changed. We are no longer in the throes of a global pandemic; world leaders are dealing with multiple competing crises, and the global health landscape appears increasingly complex as organisations grapple with optimally prioritising limited funds and contend with multiple needs and threats. But we know that future epidemics and pandemics are not just likely; they are inevitable.”

He said IPPS’ annual reports are an opportunity to reflect on progress made the year before and set priorities for the following year.

What happened in 2023?

In 2023, progress was made in several areas, the report highlighted, including the first US Food and Drug Administration-approved Chikungunya vaccine and Phase 1 trials for Crimean-Congo Haemorrhagic Fever (CCHF) vaccines. Moreover, the report showed solid political support for the 100DM from the G7 and G20.

“2023 saw strong progress in epidemic and pandemic vaccine research in support of the 100 Days Mission, including investments to advance the next-generation of mRNA and thermostable technologies, a groundswell of support for regionalised manufacturing and the growing use of artificial intelligence to accelerate vaccine design,” said Dr Richard Hatchett, CEO of the Coalition for Epidemic Preparedness Innovations (CEPI).

Therapeutics Roadmap & Scorecard

Two other publications were launched alongside the report on Tuesday: The 100DM Therapeutics Roadmap and the 100DM Mission Scorecard.

The roadmap was developed with advisors and partners, including the INTREPID Alliance, Unitaid, the Drugs for Neglected Diseases Initiative (DNDi), the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), the Medicines Patent Pool (MPP) and the Rapidly Emerging Antiviral Drug Development Initiative (READDI).

“The roadmap marks the start of a more coordinated approach to pandemic therapeutics development,” IPPS explained. “It aims to provide a springboard for action and collaboration, with a headline goal of developing at least two ‘Phase 2 ready’ therapeutic candidates for each of the top 10 WHO priority pathogen families, while also focusing on the optimisation of monoclonal antibodies and the promotion of new, disruptive technologies.”

The scorecard aims to evaluate the pipeline thoroughly concerning WHO R&D Blueprint pathogens with pandemic potential. Policy Cures Research’s analysis reveals a scarcity of approved products beyond COVID-19 and the Ebola virus Zaire strain. Furthermore, it underscores a worldwide demand for increased funding for WHO Blueprint pathogens, excluding COVID-19.

From 2019 to 2022, COVID-19 witnessed an investment of US $14.5 billion, a figure eight times higher than the combined investment in the other nine pathogens, the scorecard showed. This stark contrast underscores the imperative for more diversified funding sources, emphasising a potential risk to global preparedness.

Reactive funding

The scorecard showed that funding for epidemic diseases is also highly reactive.

“We have not yet adopted a preparedness approach for Research and Development,” the scorecard said.

Most of the available funding is generally provided by public funders, mainly the United States, which makes this funding vulnerable to political shifts. Moreover, regarding funding, vaccine R&D is the most advanced space. There is also more product R&D and WHO Target Product Profiles (TPPs) for nearly all pathogens.

In contrast, the scorecard showed that therapeutics R&D lags with few approved products, clinical candidates, and only one WHO TPP. The analysts indicate this is likely because of a lack of unified leadership around therapeutics, such as CEPI providing vaccines and FIND providing diagnostics.

Pathogens with more significant outbreaks and perceived as a greater risk to national biosecurity have more mature pipelines. In addition, funding for platform technologies to support “Disease X” has grown since 2019, and these are being used to develop products for eight priority pathogens.

“These should benefit R&D for other pathogens, but this is not yet routine,” according to the scorecard.

“The 100 Days Mission is a welcome complement to WHO’s work with partners on the diseases that pose the greatest pandemic risk, for which there are no or insufficient countermeasures,” noted Sir Jeremy Farrar, Chief Scientist at the World Health Organization (WHO). “To rapidly and equitably prepare for and respond to outbreaks of pathogens with pandemic potential, we must now sustainably invest, particularly in basic science, R&D and distributed manufacturing, including the neglected areas of pandemic therapeutics and diagnostics, as well as vaccines.”

What’s next?

The 100DM team will urge the G7 and G20 to catalyse coordinated international action and will call for political commitment to building virtual prototype libraries of pandemic therapeutics, diagnostics, and vaccines. It will also push the need to work with the private and philanthropic sectors.

The IPPS identified four goals for 2024:

• Greater coordination and investment in the therapeutics pipeline to operationalise the 100DM Therapeutics Roadmap due to the need for more funding and coordination. The report asserts that a coalition is growing around the 100DM Therapeutics Roadmap, which sets out an end-to-end plan and investment case of what is needed to reach the updated goal of at least two ‘Phase 2 ready’ therapeutic candidates for the top 10 priority pathogen families.
• Sufficient funding to implement the 100DM diagnostics framework, including supporting FIND’s initial ask of US $80-100 million. There are only four WHO priority pathogens for which they are approved diagnostics, and funding is waning.
• Greater regulatory alignment and adoption of preparatory regulatory approaches. The world would start collecting data on the safety and efficacy of prototype pandemic countermeasures when a pandemic is declared.
• Strengthening of sustainable regional and global clinical trial infrastructure to enable the rapid testing of products in humans during an outbreak.

“In 2024, under WHO leadership, practical discussions on pre-agreeing master trial protocols for emergency use should take place alongside support for regional authorities to maintain sustainable clinical trial capacity with joint ethics reviews,” according to IPPS.

“We hope that by the end of 2024, each of the four areas will have a clear overall lead, a credible plan, and the funding necessary to make progress,” Vallance said.

“Infectious diseases are one of the greatest health challenges of our time, causing around a quarter of all deaths around the world and particularly impacting vulnerable populations in low-income countries,” added Dr John-Arne Røttingen, CEO of Wellcome.

“It’s vital that pandemic preparedness stays on the agenda in 2024, with governments, industry, and philanthropy stepping up to invest in the development of new diagnostics, treatments, and vaccines.”

“Today’s report should act as a clarion call for global leaders, who must now urgently refocus on the practical steps needed to better prepare for the next pandemic, concluded Thomas Cueni, IFPMA Director General.

“Science and innovation delivered at record speed and scale against COVID-19. We must preserve what made this possible whilst taking practical steps to address the inequity we saw in the rollout of vaccines and treatments if we are going to meet the ambitious goals set out by the 100 Days Mission.

“Pharmaceutical companies have backed the ambition of the Mission since it was set out in 2021. It’s becoming increasingly clear that governments must learn the right lessons from our collective response to the COVID pandemic if we are going to achieve this shared goal.”

Image Credits: Nana Kofi Acquah.