Mpox Day 75: The Landscape of Diagnostics and Recent Developments

October 28, 2024

100 Days Mission Mpox Clock: Day 75

The 100 Days Mission (100DM) clock for mpox started on 14th August 2024, following WHO’s declaration of mpox as a public health emergency of international concern (PHEIC), and Africa CDC’s declaration of mpox as a Public Health Emergency of Continental Security (PHECS) the day before.

Today, on Day 75 of the outbreak, we provide our final major update before day 100 on 21st November – a deep dive on the landscape of diagnostics and recent developments across all three tools. There have been several major developments since Day 60:

  • WHO lists Roche Molecular Systems’ cobas MPXV Qualitative assay and Cepheid’s Xpert mpox molecular test under Emergency Use Listing
  • Contipharma receives market authorisation for its LAMP and Antigen RDT in the DRC
  • SIGA enters into Exclusive License Agreement with Vanderbilt University for Novel Poxvirus Monoclonal Antibodies (mAbs)
  • Bavarian Nordic receives WHO prequalification for mpox vaccine (Jynneos/MVA-BN)
  • WHO approves Bavarian Nordic’s mpox vaccine for adolescents aged 12 to 17
  • UK announces £9m support package to tackle mpox in central Africa, including deployment of technical experts to support Africa CDC’s response
  • EU provides €20 million additional funding towards the Africa CDC-WHO mpox preparedness and response plan.

It is crucial to remember that while the 100DM goal is to have diagnostics, therapeutics, and vaccines (DTVs) approved and ready to scale up within 100 days, the ‘Second 100 Days’ are equally critical for enabling scaled manufacturing and rapid roll-out of products to the communities that need them. The groundwork being laid now through these initiatives and partnerships is essential for ensuring effective last-mile delivery to affected populations.

These updates are intended to support the work of partners and key initiatives such as WHO’s i-MCM-net, the mpox Access and Allocation Mechanism (AAM), their 6-month Global Strategic Preparedness and Response Plan and the WHO & Africa CDC joint continental 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.

We are open to feedback on the accuracy of our data, please get in touch (info@ippsecretariat.org) if you have information to share.

Previous updates:

Overview: the status of DTVs

 

Diagnostics:

On Day 75 of the mpox response, diagnostics remain central to controlling the outbreak, with notable advancements, but there are still challenges. While PCR continues to be the gold standard for mpox testing, the need for accessible, rapid diagnostics in lower-resource settings emphasises the importance of Point-of-Care (PoC) solutions. FIND’s landscape analysis now includes over 225 mpox diagnostic tests, reflecting a marked increase and showing promising options among PoC molecular tests and antigen rapid diagnostic tests (RDTs), though further evaluations are essential to address concerns regarding performance and clade differentiation.

Africa CDC has also released an updated list of available molecular diagnostic tests for mpox recommended by its Diagnostic Advisory Committee based on performance and clade detection capabilities. This updated list supports healthcare systems in identifying reliable diagnostic options amid an evolving outbreak.

Efforts to build diagnostic capacity across affected regions continue. Africa CDC has facilitated the procurement of over 42,000 test kits and 21,000 sequencing reagents, and trained over 200 laboratory personnel, expanding local diagnostic capacity, and supporting decentralisation efforts.

These collective advancements in diagnostics, regulatory guidance, and capacity building mark meaningful steps toward effective and accessible diagnostic tools for mpox. For more detail on the status of diagnostics for the mpox response, see the diagnostics deep dive section below.

 

Therapeutics:

On Day 75, the global regulatory landscape for mpox therapeutics remains limited. While tecovirimat is approved for mpox treatment in the EU and UK, neither it nor brincidofovir has FDA approval for mpox in the US. Access in the US is limited to special programs: tecovirimat through CDC’s EA-IND protocol and brincidofovir via FDA’s e-IND program.

The INTREPID Alliance’s 2024 landscape analysis for priority viruses of pandemic potential reveals a critically limited development pipeline for mpox, with only one new compound (ASC10) in clinical development and just four antivirals among ten compounds in preclinical evaluation. Development remains concentrated in high-income countries, with 45% of developers in the US and 35% in China. While early preclinical investigations into repurposing existing cancer therapies have shown encouraging outcomes, advancing these insights toward clinical trials faces notable funding constraints.

Several trials are underway to further evaluate tecovirimat as a treatment for mpox, with a focus on understanding how disease severity and participant characteristics may impact clinical outcomes. Additional studies are also assessing other potential therapeutic agents for mpox. However, downstream factors such as cost, access, and availability are critical considerations in prioritising future investments in therapeutics.

Some progress has been made in new therapeutic approaches, with SIGA entering an exclusive license agreement with Vanderbilt University for novel poxvirus monoclonal antibodies, though manufacturing and access challenges remain.

 

Vaccines:

On Day 75, MVA-BN remains one of three WHO-Listed Authority approved vaccines (alongside ACAM2000 and LC16m8) to have started vaccination delivery. Since the last major update on Day 45, there have been significant developments: Bavarian Nordic received WHO prequalification for their Mpox vaccine (MVA-BN), and WHO has approved its use for adolescents aged 12 to 17. Both ACAM2000 and LC16m8 remain under EUL review, with the results of their respective reviews expected to be released in the coming weeks.

MVA-BN vaccination programs have begun in affected countries, with Rwanda and the DRC starting to vaccinate high-risk populations. Delivery has expanded with 265,000 doses of MVA-BN delivered to the DRC and 5,420 doses to Rwanda. Access continues through multiple funding streams including but not limited to HERA, USAID, Bavarian Nordic, and Gavi/UNICEF.

Numerous vaccines are currently in clinical trials, including the approved MVA-BN, ACAM2000, and LC16m8, alongside newer candidates like RNA-based BNT166a and mRNA-1769.

 

Deep Dive: Landscape of mpox diagnostics

As mpox remains a persistent global health threat, the ability to diagnose quickly and accurately is critical in controlling its spread and managing public health responses. This update focuses on the current state of diagnostics, emphasising the importance of Point-of-Care (PoC) tools, existing challenges, and efforts to scale diagnostic capacity.

 

The Importance of Diagnostics in the mpox Response

Diagnostics are pivotal in outbreak response because they allow for the early detection, isolation, and treatment of infected individuals. Diagnostic tools identify cases accurately and swiftly, enabling patients to be treated and health systems to break transmission chains, especially in the hardest-hit areas. Without accessible diagnostics, countries face delays in outbreak management, leading to further community spread and higher morbidity.

 

Molecular and Antigen-based Diagnostics:

FIND’s diagnostic landscape updates show significant advances in mpox-related tests:

  • 157 molecular tests have been identified, including 7 true PoC tests, 32 near-PoC, and 118 lab-based
  • 68 antigen rapid diagnostic tests (Ag RDTs) have been identified, though they struggle to differentiate between viral clades.

Mpox diagnostics encompass various technologies, with PCR tests and antigen rapid diagnostic tests (Ag RDTs) representing two distinct categories. PCR tests, which remain the gold standard, include subcategories such as lab-based, near-PoC, and PoC solutions. These subcategories provide faster results and are essential in settings with limited healthcare infrastructure, where laboratory access is a major challenge. For instance, near-PoC molecular tests like GeneXpert are already available in the DRC and offer promising performance comparable to traditional lab-based PCR tests. On the other hand, the value of Ag RDTs is still unclear, and further performance assessment is required.

 

Point-of-Care (PoC) Testing: Why It’s Crucial

Point-of-Care diagnostics, particularly for viral outbreaks, can diagnose cases directly at the site of care. PoC testing offers several advantages:

  1. Rapid Results: Results are available in under an hour, enabling timely clinical and public health decisions.
  2. Accessibility in Remote Areas: PoC tests do not require sophisticated infrastructure, which makes them ideal for deployment in rural and underserved regions, expanding testing coverage.
  3. Ease of Use: Most PoC tests are designed for use by minimally trained personnel, making them suitable for field or low-resource settings.

In the current mpox response, PoC tools would be instrumental in reaching populations that do not have access to centralised laboratories. However, other than the DRC, which has approved a PoC test for mpox, many regions still face barriers to accessing reliable PoC diagnostic tools, highlighting the urgency of developing and scaling such solutions.

 

Regulatory Landscape and Test Approvals

The regulatory landscape for mpox diagnostics spans multiple jurisdictions and approval types, from stringent regulatory authorities to country-specific authorisations. These approvals enable different paths to market access and implementation:

Key regulatory approvals include:

  • Conformité Européenne In-Vitro Diagnostic Device Directive (CE-IVDD): 76 self-certified tests, enabling marketing in the European Economic Area
  • US FDA Emergency Use Authorisation: Four commercial tests approved.
    • Abbott (Alinity M MPXV)
    • Roche (Cobas MPVX)
    • Diacarta Inc (QuantiVirus)
    • Cepheid (Xpert Mpox)
  • WHO Emergency Use Listing: Three tests approved (Abbott Alinity M MPXV, Roche Cobas MPVX, and Cepheid Xpert Mpox), with two more under.

 

Current Challenges in mpox Diagnostics

Despite advancements, several challenges persist in deploying effective diagnostic tools, particularly PoC tests:

  • Clade Differentiation: Few PoC tests, particular true PoC, are able to distinguish between viral clades at the moment, which limits their utility in identifying specific strains of mpox.
  • Antigen detection: Given cross-reactivity to many orthopoxvirus species and previous studies showing poor sensitivity to stored clinical samples, whether antigen-detecting PoC can meet sensitivity requirements for widespread use remains unclear.
  • Regulatory Approvals: While testing options continue to expand, the approval process takes time, and some regions have limited access to newer diagnostic tools. Due to regulatory requirements, the timeline for test deployment in affected areas can sometimes be lengthy.
  • Access to samples: Access to mpox viral strains and clinical specimens for commercial purposes has been a barrier for developing and validating new diagnostic tests. While exporting strains for R&D purposes remains challenging, clade 1a and 1b isolates – generously shared by the DRC – have been available through the WHO Biohub for non-commercial research since before the PHEIC was declared on August 14th. These isolates have been distributed to over 20 countries requesting either live virus, DNA material, or both. However, access pathways for commercial developers and clinical specimens remain areas for improvement.
  • Training and Capacity Building: Ensuring that local health workers and laboratory personnel are trained to handle, process, and interpret tests remains a critical issue in many affected regions.
  • Centralised Testing: Reliance on centralised laboratories delays diagnosis and impacts case confirmation, clinical care, and contact tracing. For example, DRC’s move to decentralise testing through eight additional laboratories across five provinces has shown how critical local testing capacity is – increasing samples analysed from 9,700 to over 11,400 in just nine days.

 

Capacity-Building Efforts and Progress

Significant efforts are being made to enhance diagnostic capabilities across affected countries. The Africa CDC has played a leading role, working with various partners to strengthen local capacity:

  • Procurement and Distribution: Over 42,000 tests, including GeneXpert cartridges, have been procured. In addition, sequencing reagents for 21,000 sequences have been distributed to boost genomic surveillance capabilities.
  • Emergency Use Listing: WHO launched its emergency use listing process (EUL) for mpox molecular tests in September 2024, an essential step in ensuring the availability of well-performing diagnostics for use in affected countries.
  • Local Manufacturing and Evaluation: Africa CDC has completed the evaluation of a locally manufactured PCR kit for mpox from Morocco, which showed 100% sensitivity and specificity. This is a critical step toward ensuring sustainable diagnostic capacity across Africa.
  • Rapid Antigen Test: A locally manufactured rapid antigen test from Kenya is currently under evaluation, with the protocol for its assessment finalised. In addition, 1 Ag RDT from Contipharma (Monkeypox Virus Antigen Rapid Test Kit) has received market access authorisation in DRC.
  • Training Initiatives: Africa CDC has provided training to over 212 laboratory personnel in laboratory biosafety, sample collection, molecular detection, and sequencing, helping to equip countries with the necessary skills to manage both mpox and other viral outbreaks.

 

Outlook: How Long Until We Have More Effective PoC Tests?

Looking ahead, the trajectory of mpox diagnostics is focused on expanding decentralised testing and scaling up PoC solutions. Organisations such as the Africa CDC, WHO and FIND are leading the charge in local manufacturing and collaborative research, essential to closing the gap in access to diagnostic tools.

With ongoing evaluations of rapid antigen and PoC molecular tests and the deployment of locally manufactured kits, we anticipate more PoC solutions will soon become available. The continued focus on capacity building, both in terms of infrastructure and workforce development, is key to ensuring these tools can be implemented widely.

The demand for true PoC solutions is expected to grow, particularly in regions with limited infrastructure. Regulatory approvals and emergency use listings are accelerating for key tests, such as those from Abbott, Roche, and Cepheid, with a LAMP and antigen rapid test from Contipharma already receiving approval in the Democratic Republic of Congo (DRC).

 

Conclusive Remarks

Since the beginning of the outbreak, IVD manufacturers have made enormous efforts to develop PoC Mpox tests, as seen by a significant increase in commercially available PoC molecular tests and Ag RDTs. Indeed, there is a near-PoC tests in use for the response in DRC – the Xpert Mpox test from Cepheid. However, high uncertainty remains around the performance of many of these tests, particularly regarding their ability to detect and differentiate between MPXV clades, limiting their registration and adoption in affected countries. Additional data to support expert regulatory assessments may help guide recommendations for a prequalification process for these PoC Mpox tests. With the continued efforts of organisations like FIND, Africa CDC, and WHO on test evaluations and partnerships with local manufacturers, the goal of achieving widespread access to reliable diagnostics is becoming more attainable.

As we move forward, diagnostics will continue to play a critical role in managing the Mpox outbreak, guiding public health interventions and helping to control the spread of the virus. While much progress has been made, ensuring access to effective true PoC diagnostics remains a top priority for the global health community.