Mpox update – August 2024

Two years after the World Health Organization (WHO) declared a global health emergency over an outbreak of the mpox (previously known as monkeypox) virus, a deadlier strain has emerged.¹ Clade 1b was detected in the Democratic Republic of the Congo (DRC) in September 2023.⁵

This follows the WHO declaring an end to the 2022 mpox global health emergency in May 2023.  

Industry response

While the US Centers for Disease Control and Prevention (CDC) reported no cases of this clade I strain outside central and east Africa as of 7 Aug,² on 14 Aug, the WHO deemed the active strain as a public health emergency of international concern (PHEIC), urging that a “coordinated international response is needed to stop these outbreaks and save lives.”³ The next day, the first positive case of clade 1b mpox was reported on European soil in Sweden.⁴

The Institut Pasteur President, Yasmine Belkaid, remarked that the case in Sweden is a reminder that “tackling [mpox] requires a comprehensive, sustained, long-term response. Growing ecosystem disruption and the continued development of international trade and travel make this risk more pressing every day. We need to play our part by supporting scientific research on infectious diseases in the fields of virology, immunology and vaccinology.”⁴

“The current upsurge of mpox in parts of Africa, along with the spread of a new sexually transmissible strain of the monkeypox virus, is an emergency, not only for Africa, but for the entire globe. Mpox, originating in Africa, was neglected there, and later caused a global outbreak in 2022. It is time to act decisively to prevent history from repeating itself,” stated International Health Regulations (IHR) Emergency Committees Dimie Ogoina, Committee Chair Professor.³

Recently, the WHO launched a global Strategic Preparedness and Response Plan aimed at halting outbreaks of the virus via human-to-human transmission. The publication emphasised strategic leadership, timely evidence-based guidance, and access to medical countermeasures for the most at-risk groups in affected countries.⁵

Preventing spread of the mpox virus

To help prevent more cases of the virus, the CDC recommended that individuals who have had exposure to the virus and those at risk of infection are given two doses of biotech Bavarian Nordic’s vaccine JYNNEOS^® (MVA-BN).²

In the first meeting of the International Health Regulations (2005) Emergency Committee about the 2024 outbreak, the WHO Director-General Dr Tedros Adhanom Ghebreyesus spoke about the 12-month extension of the current standing recommendations for mpox, which were set to expire on 20 August 2024. The recommendations included: “conduct clinical trials of medical countermeasures, including diagnostics, vaccines and therapeutics, in different populations, in addition to monitoring of their safety, effectiveness and duration of protection.⁶

Securing supply of mpox vaccines

Following the concerns around the spread of the outbreak, to support the supply of vaccines for the disease, earlier this month the WHO Director-General declared that he had put into motion the Emergency Use Listing (EUL) for mpox vaccines.⁷ Soon after, Dr Ghebreyesus invited manufacturers to submit their interest for their vaccines to be listed for emergency use.⁸

On 29 Aug, Emergent BioSolutions Inc. received approval from the US Food and Drug Administration (FDA) for its supplemental Biologics License Application (sBLA) for an indication expansion for ACAM2000^®(Smallpox and Mpox (Vaccinia) Vaccine, Live) to include individuals deemed at high risk of mpox infection. This was based on the company’s Expression of Interest application to be included on the WHOs EUL.  

“This expanded indication for ACAM2000 comes at a critical time as the global health community comes together to ensure an effective and cohesive response to the recent upsurge in mpox cases. We believe Emergent is poised to support the global response needed by actively engaging with world health leaders, as well as deploying product currently available in inventory based on the needs, as well as the ability to increase supply” commented Joe Papa, President and CEO of Emergent. 

Pharmaceutical company NanoViricides highlighted the need for new treatments to manage the recurring mpox pandemics, since there is a short supply of the limited vaccines that are available, which are developed as smallpox vaccines.⁹

Following the WHO’s PHEIC announcement, the company considered that its novel investigational antiviral NV-387 is eligible for evaluation for Monitored Emergency Use of Unregistered and Investigational Interventions (MEURI), as a treatment for the virus. The experimental drug has completed a Phase I study. Promising animal studies of NV-387 have shown that the drug was “as effective as the current approved drug tecovirimat” when emulating the direct skin infection by the virus. This is notable because “direct skin infection is thought to be the major mode of transmission of the virus in the current epidemic of MPOX Clade 1 and Clade 1b” according to NanoViricides.⁹

Another promising vaccine candidate for mpox, TNX-801, developed by Tonix Pharmaceuticals, has similarities to the original smallpox vaccine. This drug was the only vaccine to successfully eliminate a contagious viral pathogen, according to Tonix. In contrast to mRNA vaccines, TNX-801 is designed to elicit a robust T-cell response, “facilitating long-term immunity and potentially eliminating the need for repeated boosters”. For example, pre-clinical data shows that the drug “significantly reduced viral shedding, suggesting that it can block forward transmission”.¹⁰

Pandemic preparedness

Commercially, Bavarian Nordic received a substantial contract to supply smallpox and mpox vaccines for undisclosed European Country on the 21 Aug.¹¹ Less than a week later, the biotech’s JYNNEOS vaccine was authorised in Singapore to immunise individuals against mpox and smallpox.¹²

Positively, Bavarian Nordic shared that it “can still supply up to 10 million doses of our smallpox and mpox vaccine by the end of next year, with two million doses of this capacity available during the remaining part of this year,” Paul Chaplin, President & CEO of Bavarian Nordic commented.¹¹

Regarding R&D, the UK Health Security Agency (UKHSA)’s Vaccine Development and Evaluation Centre (VDEC) is a key part of supporting pandemic preparedness, and for the development of vaccines to immunise against pathogens that pose a pandemic risk, such as mpox. The centre not only has capability for testing emerging vaccines against new variants, but according to Professor Dame Jenny Harries, Chief Executive of UKHSA, provides “multiple critical early pre and post clinical research and evaluation studies in a single research facility.”¹³

In conclusion, WHO confirmed that “to ensure a coordinated and effective response to the ongoing outbreak, the organisation will establish integrated incident management teams (IMST) at the global, regional, and country levels as needed”. For example, The Global Mpox IMST will ensure a unified and effective global response.⁵

References

1. The Threat of Mpox Has Returned but Public Knowledge About It Has Declined. [Internet] The Annenberg Public Policy Center. 2024. [cited 2024Aug]. Available from: https://www.annenbergpublicpolicycenter.org/the-threat-of-mpox-has-returned-but-public-knowledge-about-it-has-declined
2. Mpox Caused by Human-to-Human Transmission of Monkeypox Virus in the Democratic Republic of the Congo with Spread to Neighboring Countries. [Internet] CDC. 2024. [cited 2024Aug]. Available from: https://emergency.cdc.gov/han/2024/han00513.asp#print
3. WHO Director-General Declares Mpox Outbreak A Public Health Emergency Of International Concern. [Internet] WHO. 2024. [cited 2024Aug]. Available from: https://www.who.int/news/item/14-08-2024-who-director-general-declares-mpox-outbreak-a-public-health-emergency-of-international-concern
4. Mpox Outbreak: “We Are Ready To Test And Vaccinate”. [Internet] The Institut Pasteur. 2024. [cited 2024Aug]. Available from: https://www.pasteur.fr/en/press-area/press-documents/mpox-outbreak-we-are-ready-test-and-vaccinate
5. Global Strategic Preparedness And Response Plan Launched By WHO To Contain Mpox Outbreak. [Internet] WHO. 2024. [cited 2024Aug]. Available from: https://www.who.int/news/item/26-08-2024-global-strategic-preparedness-and-response-plan-launched-by-who-to-contain-mpox-outbreak
6. First Meeting Of The International Health Regulations (2005) Emergency Committee Regarding The Upsurge Of Mpox 2024. [Internet] WHO. 2024. [cited 2024Aug]. Available from: https://www.who.int/news/item/19-08-2024-first-meeting-of-the-international-health-regulations-(2005)-emergency-committee-regarding-the-upsurge-of-mpox-2024
7. WHO Invites Mpox Vaccine Manufacturers To Submit Dossiers For Emergency Evaluation. [Internet] WHO. 2024. [cited 2024Aug]. Available from: https://www.who.int/news/item/09-08-2024-who-invites-mpox-vaccine-manufacturers-to-submit-dossiers-for-emergency-evaluations
8. First Invitation To Manufacturers Of Vaccines For Prevention Against Mpox To Submit An Expression Of Interest For Evaluation By The World Health Organization. [Internet] WHO. 2024. [cited 2024Aug]. Available from: https://extranet.who.int/prequal/sites/default/files/document_files/call-for-eoi-mpox-vaccines-2024-08-09.pdf
9. MPOX is Emerging as a Global Threat – NanoViricides Investigating MEURI Protocol for Using NV-387 to Treat MPOX. [Internet] Nanoviricides. 2024. [cited 2024Aug]. Available from: https://www.pharmiweb.com/press-release/2024-08-26/mpox-is-emerging-as-a-global-threat-nanoviricides-investigating-meuri-protocol-for-using-nv-387-t
10. Modern Twist to Centuries-Old Smallpox Vaccine Poised to Combat Deadly Mpox Strain as WHO Declares Global Emergency. [Internet] Tonix Pharmaceuticals Holding Corp. 2024. [cited 2024Aug]. Available from: https://www.pharmiweb.com/press-release/2024-08-23/modern-twist-to-centuries-old-smallpox-vaccine-poised-to-combat-deadly-mpox-strain-as-who-declares-g
11. Bavarian Nordic Receives 440,000 Dose Contract to Supply Smallpox and Mpox Vaccines for Undisclosed European Country. [Internet] Bavarian Nordic. 2024. [cited 2024Aug]. Available from: https://www.bavarian-nordic.com/investor/news/news.aspx?news=6972
12. Bavarian Nordic Receives Approval of Smallpox and Mpox Vaccine in Singapore. [Internet] Bavarian Nordic. 2024. [cited 2024Aug]. Available from: https://www.bavarian-nordic.com/investor/news/news.aspx?news=6983
13. New Vaccine Development Centre To Strength UK’s Capabilities. [Internet] European Pharmaceutical Review. 2023. [cited 2024Aug]. Available from: https://www.europeanpharmaceuticalreview.com/news/185554/new-vaccine-development-centre-to-strength-uks-capabilities/