Day 15 of the 100 Days Mission Mpox Clock
On 14th August 2024, WHO declared mpox a public health emergency of international concern (PHEIC), following Africa CDC’s declaration of mpox as a Public Health Emergency of Continental Security (PHECS) the day before. This marked the start of the 100 Days Mission clock, and the IPPS published a statement on the state of Diagnostics, Therapeutics and Vaccines (DTVs) at Day 0.
Leading up to Day 100 on 21st November, we will provide regular updates on the status and progress of mpox DTV availability and highlight specific priority actions to ensure products are available to those who need them. These updates are intended to support the work of partners and key initiatives such as WHO’s i-MCM-net and their 6-month Global Strategic Preparedness and Response Plan. The data used to inform this update has been collected through desk research using public information and direct updates from implementing partners of the 100DM. Please find the latest updates at https://ippsecretariat.org/news/
While the 100DM goal is to have DTVs approved and ready to scale up within 100 days, the ‘Second 100 Days’ are also critical for enabling scaled manufacturing and rapid roll-out of products to the communities that need them. Groundwork needs to be laid now for this last-mile delivery to happen. For vaccines, where we have approved products, the focus has already shifted towards scale-up and distribution.
Epidemiology (as of 29th August)
The number of cases, deaths and countries affected can be tracked on the WHO mpox tracker site. The African region is updating data on a weekly basis and global data is currently being updated monthly. All totals you see are between January 2022 and August 2024. As the WHO website itself states “A significant number of suspected cases, that are clinically compatible with mpox are not tested due to limited diagnostic capacity and never get confirmed. Work on integrating these data is currently ongoing and will be included in future updates.” This is precisely why IPPS are advocating for accelerated development of accurate, rapid point-of-care (POC) testing.
Overview: the status of DTVs
On Day 15, there are no approved antigen-based rapid diagnostic tests for all mpox clades. Diagnostics are a critical front-line defence against infectious disease spread. PCR is the gold standard diagnostic test for mpox. Accurate antigen-based rapid diagnostic tests (RDTs) are particularly important for testing in remote areas with limited laboratory capacity, and to understand, slow down or prevent the spread of the disease through the population, and link patients to treatments.
FIND is working with Africa CDC in undertaking a landscape analysis of the current Near Point of Care and True Point of Care tests that are commercially viable, planning for independent evaluation and optimisation of the most promising tests to help accelerate approvals, and seeking funding for rapid optimisation of tests if no tests meet the WHO’s Target Product Profile. However, it still looks challenging to roll out PoC tests before the end of 2024.
WHO has requested manufacturers of mpox in vitro diagnostics to submit expressions of interest for Emergency Use Listing (EUL) to enhance access to effective diagnostics. This move is part of broader efforts to expand testing capacity, improve case detection, and respond to the rising demand for diagnostic tests, especially in heavily affected regions.
On Day 15, there are no SRA-approved therapeutics specifically for mpox. Tecovirimat, approved by the EMA, is a smallpox drug approved under animal rule for mpox.
Therapeutics are key to treating diseases with pandemic potential, and benefit those who fall ill and need effective treatment, even if a vaccine exists. Antiviral drugs can also be deployed as pre-and post-exposure prophylaxis, especially for health workers, vulnerable groups, and those who cannot mount an effective immune response to a vaccination.
Long-awaited initial results for Tecovirimat against Clade 1 were disappointing, and though safe and well tolerated, it showed no efficacy against placebo. However, several follow-up trials are planned to further investigate Tecovirimat as a mpox treatment, and whether disease severity or participant characteristics will lead to significant differences in clinical outcomes. Additional trials are soon to begin on Brincidofovir, another smallpox therapeutic, which may be able to be used in adolescents.
Work is underway to explore whether monoclonal antibodies may play a role in this mpox response, albeit with questions needing answering around speed and accessibility.
On Day 15, the 3 stringent regulatory authority (SRA) approved vaccines (MBA-BN, ACAM2000 and LC16m8) are still not available and accessible to all affected countries.
Applications submitted to WHO’s call for EUL will be reviewed with the outcomes to be shared in September. WHO is also developing an Access and Allocation Mechanism (AAM) to get vaccines to all affected countries.
On 27th August, the African Medicines Regulatory Harmonization Initiative (AMRH) issued a call for manufacturers of vaccines and therapeutics to apply for EUL on the continent. Any product which secures EUL will be published on the African Union Development Agency (AUDA NEPAD) website and will inform Africa CDC’s Pooled Procurement Mechanism.
Whilst vaccines are important to infectious disease preparedness and response, they alone cannot ensure complete control over viral spread or provide immediate protection to populations.
Priority actions for the next 85 days
In light of the current status of DTVs, and following on from the recommendations in IPPS’ Day 0 statement, we continue to encourage the international community to focus on the following updated priority actions over the next 85 days:
Deep Dive: the status of DTVs
Diagnostics
Key challenges and opportunities
Whilst there are effective PCR tests, there is an urgent need for point-of-care (PoC) diagnostics, particularly antigen-based RDTs, which can distinguish between Clade 1/1b and Clade 2 and can be used in both home and clinic settings. This is particularly important in remote regions with limited or no access to laboratory facilities or PCR tests.
Over the next 85 days, we must
- support the development and approval of rapid diagnostic tests, and
- increase access to existing PCR-based point-of-care tests.
Key to achieving the above will be mapping the landscape of diagnostics against mpox, and conducting an assessment/evaluation of PoC diagnostic tests to identify promising solutions which align with WHO’s Target Product Profile.
Therapeutics
Progress, key challenges and opportunities
Although Tecovirimat is currently the only SRA-approved therapeutic for mpox, the recent PALM007 trial found it to be ineffective against Clade I. However, several ongoing trials are investigating its efficacy and safety across different population groups and against Clade I, Clade II, or both. Notable examples include STOMP USA, Unity, ISARIC, EPOXI, PLATINUM-CAN, PLATINUM UK, MOSA, and another arm of the PALM007 trial. These trials, and other planned trials, may also help provide a better picture of Tecovirimat’s efficacy, including whether Tecovirimat is more effective if given at an earlier stage of infection or as post-exposure prophylaxis, or as combination therapy with other therapeutics. Additionally, there are newly established trials of other repurposed therapeutics such as Brincidofovir (MOSA).
There is currently limited information about novel therapeutics in the pipeline for mpox. The INTREPID Alliance, who mapped the anti-viral candidate landscape of therapeutics for pathogens with pandemic potential, will also be undertaking a similar mapping of anti-viral candidates in the pipeline for mpox, to be published on the 2nd of September.
Additionally, monoclonal antibodies (mAbs) offer a promising alternative to antiviral therapies. Their potential for rapid deployment as post-exposure prophylaxis, treatment, or even as a preventive measure in high-risk populations and healthcare workers is significant. mAbs could be especially valuable in paediatric cases, where safety is a primary concern. Currently, the only potential mpox mAbs are in the pre-clinical stage and would need rapid investment to accelerate trials to play a role in this response.
Ongoing research shows that mAbs are effective in neutralizing the virus and providing targeted protection, which could fill critical gaps left by the lack of effective antiviral treatments (mAb study 2024, mAb study 2016). Landscape analysis of potential mAbs in the pipeline should be made to aid the response to mpox.
Over the next 85 days, we must
- identify promising anti-virals and potential mAbs in the pipeline for mpox, and
- develop innovative trials to repurpose candidate anti-virals and mAbs for mpox in different population groups including children.
Mapping the landscape of candidate anti-virals and potential mAbs for mpox to conduct clinical trials to assess their safety and effectiveness will be key to providing therapeutic options for the response to mpox.
Vaccines
Progress, key challenges, and opportunities
As there are already approved vaccine products for mpox, vaccines have a different starting point at Day 0 to therapeutics and diagnostics.
Over the next 85 days, we must ensure that vaccines:
- are approved for use and available in all affected countries,
- can be manufactured at scale, and
- delivered to the populations most affected.
Expanding vaccine availability is dependent on WHO and AUDA-NEPAD’s EUL decisions, as well as the scale of donations.
As of Day 15, all 3 approved vaccines are still not available in all affected countries. Bavarian Nordic, Emergent BioSolutions, Japan (there is yet to be an official announcement from the Government of Japan on LC16m8 donations and discussions are ongoing with DRC), Spain, European Commission, France, Germany and the USA have pledged vaccine donations to affected countries in Africa totalling over 3 million doses pledged (Mpox Vaccine Tracker: Millions Pledged, Millions to Still Be Delivered | Think Global Health). Africa CDC estimates that the need across the continent is 10 million doses. Therefore, to effectively protect populations against mpox, scaling up the production of approved vaccines, and establishing a sustainable supply chain to ensure equitable access will be key.
This may require greater regional manufacturing capacity, including via technology transfer or fill and finish for mpox vaccines which receive EUL. Bavarian Nordic has held exploratory conversations with Africa CDC on technology transfer.
There is also a greater need for evidence around the effectiveness of MVA-BN, ACAM2000 and LC16m8 specifically against Clade 1, as currently effectiveness against Clade I is assumed due to the effectiveness of the vaccines against Clade II and Smallpox.
Additionally, more studies are needed to demonstrate the effectiveness of the vaccines in children, during pregnancy, and in immunocompromised individuals. CEPI has recently funded a phase II clinical trial on the efficacy of the Bavarian Nordic vaccine on children (aged 2-12), and the European & Developing Countries Clinical Trials Partnership have just issued a funding call for a phase II vaccine trial on the efficacy of mpox vaccines during pregnancy and in children. CEPI and the Canadian Institutes of Health Research recently funded the SMART study in the Democratic Republic of Congo (DRC) and other African countries to assess the effectiveness of the Bavarian Nordic smallpox vaccine in reducing the incidence of mpox and its associated complications post-exposure.