The 100 Days Mission Clock Starts Now
On 14th August 2024, the World Health Organisation (WHO) declared Mpox a Public Health Emergency of International Concern (PHEIC) under the International Health Regulations (2005) – WHO’s highest IHR alert level. The PHEIC declaration follows the rapid spread of Mpox Clade 1 and 1b across Eastern DRC, and the first ever reported cases reported in several neighbouring countries; Burundi, Kenya, Rwanda and Uganda. This follows Africa CDC’s declaration the day before of Mpox as a Public Health Emergency of Continental Security (PHECS).
It should be acknowledged that while these declarations are critical this is not the beginning of the outbreak or the beginning of the response. Many actors including WHO, Africa CDC and national authorities have been working to bring the outbreak under control for many months. However, these declarations should be a global wake up call to the severity of the situation and the need for a globally coordinated response in solidarity with affected communities.
As the International Pandemic Preparedness Secretariat (IPPS), it is our mandate is to support the implementation of the 100 Days Mission to make diagnostics, therapeutics, and vaccines (DTVs) available as rapidly as possible in communities that need them. The declaration of yesterday’s PHEIC means the clock starts now and serves as an urgent reminder of the importance of all actors pulling together to deliver on previous commitments and embed the principles of the 100 Days Mission in as rapid and equitable a response as possible.
The goals of the 100 Days Mission are to prepare as much as possible so that within the first 100 days that a pandemic threat is declared (Day 0), the following interventions can be made available, safe, effective, and affordable:
1. Accurate and approved rapid point of care diagnostic tests
2. An initial regimen of therapeutics
3. Vaccines ready to be produced at scale for global deployment
We have a head start in some of these areas but not all.
As the world becomes increasingly interconnected, climate crisis exacerbates spread of infectious disease, thereby increasing zoonotic transmission of pathogens. This not only makes the risk of epidemics and pandemics higher, but the time between pandemics is potentially shorter. At present, we are not 100 Days Mission ready and we may not meet this ambitious target yet.
Status of Diagnostics, Therapeutics and Vaccines for Mpox on Day Zero
According to the 2023 G-FINDER survey, in its first year of recorded funding (in 2022), Mpox R&D received:
– $66 million for diagnostics, therapeutics and vaccines;
– $1.2 million for diagnostics;
– $36 million for therapeutics (including $82,000 biologics);
– $28 million for vaccines –(N.B there were already two approved vaccines).
By comparison, COVID-19 received a total of $3.7bn across all three tools $2.4bn for vaccines, $1.1 bn for therapeutics (including $222m for biologics), and $195m for diagnostics in 2022.
Despite this funding, and despite the wake up call of the 2022 PHEIC, at present, Mpox DTV access and availability is limited. DTVs, in addition to non-pharmaceutical interventions, will be crucial for a swift response.
Vaccines: There are currently two approved vaccines that are used for Mpox – Bavaria-Nordic’s modified vaccine Ankara-Bavarian Nordic (MVA-BN) JYNNEOS, and the ACAM2000 vaccine. Africa CDC has highlighted the need for more vaccines to respond to the outbreak across Africa, and has estimated that 10 million doses will be needed. Only two African countries (Nigeria and the Democratic Republic of the Congo) have granted Emergency Use Authorisation (EUA) for the JYNNEOS vaccine, meaning access across the continent is limited. IPPS welcomes WHO’s call for expressions of interest from vaccine manufacturers for EUA for the JYNNEOS vaccine, which would accelerate accessibility to African countries where national regulatory approvals are currently not yet in place.
Diagnostics: Surveillance is pivotal for understanding transmission dynamics, access to and availability of diagnostics is key to this. At present, the only WHO recommended diagnostic tests for Mpox are lab-based PCR tests – with PCR testing of skin lesions being the gold standard. The point of care diagnostics currently in the pipeline are not approved and do not yet meet WHO Target Product Profiles. Primarily lab-based testing poses challenges, as this is slow and often not available in areas with limited laboratory capacity. Development and approval of accurate, rapid, point of care diagnostics must be accelerated within the next 100 days.
Therapeutics: There are currently no approved therapeutics for Mpox. However, there has been repurposing of existing drugs and there is an investigational Mpox antiviral – Tecovirimat. However, there is still heterogeneity in the regulatory approvals and use of the drug across different countries (approved for smallpox only in US and otherwise investigational drug protocol, and approved for use for Mpox in EU). Large-scale efficacy trials are still needed. There needs to be rapid acceleration of efficacy trials for Mpox antivirals to enable EUL and distribution in affected communities within the next 100 days.
Across all three tools, in order for countries to be ready to produce DTVs rapidly, we need to ensure greater regulatory alignment between countries, and adoption of more preparatory regulatory approaches to speed up pandemic response.
Priority Actions for the Next 100 Days
IPPS welcomes the rapid actions of the WHO in convening partners through several fora such as the i-MCM-net and the ACT-A Principals group. As we work together with the 100 Days Mission implementing partners, we encourage the international community to increase and sustain both funding and political commitment for:
– Increased surveillance, laboratory testing and sequencing capacity in the immediate term to track disease progression and support non-pharmaceutical interventions.
– Accelerated development and approval of accurate, rapid point of care diagnostics.
– Accelerated development of efficacy data to enable emergency use approval of Mpox antivirals where most needed.
– Accelerated regulatory harmonisation and approval of investigational antiviral Tecovirimat
– Increased and strengthened clinical trial capacity in regions most affected.
– Accelerated regulatory approvals and data generation for the existing vaccines.
– Scaled up manufacture, procurement and roll out of vaccines, therapeutics and diagnostics once approved.
We need consistent, ambitious and sustainable investment in R&D during inter-pandemic periods to ensure we can produce DTVs as efficiently as possible when faced with a health emergency. At IPPS, we are committed to working with 100 Days Mission implementing partners to bring an end to the Mpox outbreak. IPPS encourage the international community to provide Africa CDC, WHO and affected governments with the necessary support and funding to respond effectively, whilst strengthening pandemic preparedness at national, regional and global levels.
Dr Mona Nemer, Steering Group Chair, International Pandemic Preparedness Secretariat; Chief Science Advisor of Canada
Shingai Machingaidze, Science & Technology Expert Group (STEG) Co-Chair, International Pandemic Preparedness Secretariat
Dr Victor Dzau, Science & Technology Expert Group (STEG) Co-Chair, International Pandemic Preparedness Secretariat