Monkeypox update – August 2022

On 23 July 2022, the World Health Organization (WHO) Director-General, Dr Tedros Adhanom Ghebreyesus, declared the multi-country outbreak of monkeypox a public health emergency of international concern.¹ Coming just a few years after the declaration of COVID-19 as the same kind of issue, the world is waiting with bated breath to see if the scale of the monkeypox outbreak will rival that of the ongoing pandemic caused by the coronavirus.

In a statement the Director-General explained: “WHO’s assessment is that the risk of monkeypox is moderate globally and in all regions, except in the European region where we assess the risk as high. There is also a clear risk of further international spread… So in short, we have an outbreak that has spread around the world rapidly, through new modes of transmission, about which we understand too little, and which meets the criteria in the International Health Regulations. For all of these reasons, I have decided that the global monkeypox outbreak represents a public health emergency of international concern.”¹

Alongside this declaration, sets of recommendations were made for countries based on four groups:²

• those that had not yet reported a case of monkeypox, or had not reported a case for more than 21 days
• those with recently imported cases of monkeypox and that are experiencing human-to-human transmission.
• those with transmission of monkeypox between animals and humans
• countries with manufacturing capacity for diagnostics, vaccines and therapeutics.

But what is monkeypox?

Monkeypox is a disease caused by a zoonotic orthopoxvirus (the monkeypox virus) with similar but less severe symptoms to smallpox – a related disease eradicated through vaccination campaigns by May 1980 – including a rash and fever.³ A zoonosis is a disease that is transmitted from animals to humans; in the case of monkeypox, the most likely natural reservoir is rodents, though this has yet to be confirmed.

Human-to-human transmission is limited and not regarded as sufficient to sustain an outbreak. The virus can be transmitted through contact with bodily fluids, lesions on the skin or internal mucosal surfaces, such as in the mouth or throat, as well as respiratory droplets and contaminated objects.³ 

Monkeypox is endemic in Central and West Africa, though the true burden of monkeypox is not known. There are two common subtypes (clades) of monkeypox virus: the central African (Congo Basin) clade and the west African clade, with the former thought to be more transmissible and cause more severe disease.

The viral DNA of monkeypox can be detected using polymerase chain reaction (PCR), with samples ideally taken directly from the rash – skin, fluid or crusts, or biopsy where feasible.³ The WHO suspects antigen and antibody detection methods may not be useful for this outbreak, as they do not distinguish between orthopoxviruses.³ 

Current case rates

Globally, as of 2 August 2022, 25,391 confirmed cases of monkeypox had been reported worldwide, almost 99 percent of which are in countries that have never historically reported the disease (25,047 cases).⁴

As noted, Europe has been declared at high risk from monkeypox. As of 1 August 2022, 27 EU/European Economic Area (EEA) countries had reported a total of 12,186 confirmed cases, with Spain (n = 4,298), Germany (2,677), France (2,054), the Netherlands (879) and Portugal (633), having the largest numbers.⁵ So far, just two deaths have been reported in this region, both occurring in Spain.

As of 2 August 2022, the UK had 2,739 confirmed cases,⁴ the majority occurring within London, England. The US had a total of 5,811 confirmed cases on 1 August 2022,⁶ while Asia and the Western Pacific had at least 71 cases of monkeypox confirmed across multiple countries.^4,7

Global response

In response to the outbreak, the European Medicines Agency (EMA) has announced that the remit of its Emergency Task Force (ETF) will be formally extended to deal with both COVID-19 and monkeypox.⁸ With priorities including:

• providing scientific advice and reviewing available scientific data on medicinal products that have the potential to address the emergency
• the co-ordination of independent monitoring studies on the use, effectiveness and safety of medicinal products intended to be used against monkeypox
• delivering recommendations to the Member States on the use of unauthorised medicinal products to treat or prevent the disease, when requested
• advising on clinical trial protocols and providing advice to developers on clinical trials for medicinal products intended to treat, prevent or diagnose the disease.⁸

In the EU Tecovirimat SIGA (tecovirimat monohydrate; SIGA Technologies) is a medication authorised for use under exceptional circumstances to treat smallpox, monkeypox and cowpox.

Meanwhile, across the pond, US Food and Drug Administration (FDA) Commissioner Robert Califf stated: “The FDA has been closely tracking reports of monkeypox transmissions in the United States with our federal public health partners and coordinating preparedness efforts accordingly… we already have medical products in place, specifically an FDA-approved vaccine for the prevention of monkeypox disease and an FDA-cleared diagnostic test. The FDA is using the full breadth of its authorities to make additional diagnostics and treatments available.”⁹

As of yet, there is no FDA-approved or authorised medicine for the treatment of monkeypox disease; however, TPOXX (tecovirimat), an antiviral medication, is being made available through the US Centers for Disease Control and Prevention (CDC) for compassionate use (using the Expanded Access pathway).⁹ There is currently no human data demonstrating the efficacy of TPOXX for the treatment of monkeypox, or the safety and pharmacokinetic profile, therefore the regulator stated that conducting randomised, controlled trials to assess TPOXX’s safety and efficacy in humans with monkeypox infections is essential.

Vaccine development and supply efforts

One company has been at the centre of the global response; Bavarian Nordic has received numerous orders for its smallpox vaccine a non-replicating smallpox vaccine developed in collaboration with the US government. The vaccine is approved in the US as Jynneos^® (Modified Vaccinia Ankara-Bavarian Nordic or MVA-BN), Canada as Imvamune^® (MVA-BN) and Europe as Imvanex^® (MVA-BN) for both smallpox and monkeypox. The European Commission (EC) granted the indication extension for monkeypox on 25 July 2022.¹⁰

Bavarian Nordic has ongoing supply contracts with US and Canada and has delivered the vaccine to a number of undisclosed countries globally as part of their national biological preparedness for smallpox. In recent years, smaller quantities of the vaccine have been supplied in response to sporadic cases of monkeypox.

In the ongoing 2022 monkeypox outbreak, exactly how many doses of Bavarian Nordic’s vaccine have been ordered are unclear, as there have been numerous supply deals for amounts or with countries that remain undisclosed.

Known contracts with the US bring total deliveries in 2022 and 2023 to nearly seven million doses.¹¹ These doses are to be made using already manufactured bulk vaccine, invoiced under previous contracts with US, with some of the doses to be filled and finished at the company’s new plant in Kvistgaard, Denmark, while others are filled by as US-based contract manufacturer.

Under a five-year contract with the Canadian Government, Bavarian Nordic will deliver $56 million worth of vaccine from 2023,¹² and through a contract with the European Health Emergency Preparedness and Response Authority (HERA), 109, 090 doses of vaccine will be made available to EU Member States, Norway and Iceland, with deliveries to commence immediately.¹³

An undisclosed European country has further ordered 1.5 million doses with deliveries to start in 2022 and predominate in 2023.¹⁴ A similarly undisclosed APAC nation has ordered 350,000 doses for 2023.¹⁵

In the US, a second vaccine, ACAM2000 – a live Vaccinia virus preparation manufactured by Sanofi Pasteur and delivered as a single dose, has been licensed by FDA for use against smallpox and made available for use against monkeypox under an Expanded Access Investigational New Drug application. There is a larger supply of this vaccine than Bavarian Nordic’s, according to the CDC, however it has some limitations:¹⁶

• ACAM2000 should not be used in people who have certain health conditions, such as a weakened immune system, skin conditions like eczema or other exfoliative skin conditions, or are pregnant
• Where it takes 14 days after the second dose of Jynneos to develop the maximal immune response, it takes four weeks following the ACAM2000 dose.

The WHO has asserted that the priority should now be to use existing or new vaccines against monkeypox within a framework of collaborative clinical efficacy studies. The Organization is working to facilitate the standardisation of design methods and data collection tools for clinical and outcome data and the rapid scaling of evidence generation relating to the efficacy and safety of vaccines.¹⁷

References

1. Adhanom Ghebreyesus T. WHO Director-General’s statement at the press conference following IHR Emergency Committee regarding the multi-country outbreak of monkeypox – 23 July 2022 [Internet]. Who.int. 2022 [cited 2 August 2022]. Available from: https://www.who.int/news-room/speeches/item/who-director-general-s-statement…
2. Second meeting of the International Health Regulations (2005) (IHR) Emergency Committee regarding the multi-country outbreak of monkeypox [Internet]. Who.int. 2022 [cited 2 August 2022]. Available from: https://www.who.int/news/item/23-07-2022-second-meeting…
3. Monkeypox [Internet]. Who.int. [cited 2 August 2022]. Available from: https://www.who.int/health-topics/monkeypox#tab=tab_1
4. 2022 Monkeypox Outbreak Global Map [Internet]. CDC.gov. 2022 [cited 3 August 2022]. Available from: https://www.cdc.gov/poxvirus/monkeypox/response/2022/world-map.html
5. Monkeypox multi-country outbreak [Internet]. ECDC.europa.eu. 2022 [cited 2 August 2022]. Available from: https://www.ecdc.europa.eu/en/monkeypox-outbreak
6. 2022 U.S. Map & Case Count [Internet]. CDC.gov. 2022 [cited 2 August 2022]. Available from: https://www.cdc.gov/poxvirus/monkeypox/response/2022/us-map.html
7. Asia and the Western Pacific: Confirmed monkeypox cases reported in several countries in the region through July /update 1 [Internet]. crisis24.garda.com. 2022 [cited 3 August 2022]. Available from: https://crisis24.garda.com/alerts/2022/07/asia-and-the-western-pacific…
8. EMA response to the monkeypox public health emergency – European Medicines Agency [Internet]. European Medicines Agency. 2022 [cited 8 August 2022]. Available from: https://www.ema.europa.eu/en/news/ema-response-monkeypox-public-health-emergency
9. FDA Provides Update on Agency Response to Monkeypox Outbreak [Internet]. U.S. Food and Drug Administration. 2022 [cited 9 August 2022]. Available from: https://www.fda.gov/news-events/press-announcements/fda-provides-update-agency-response-monkeypox-outbreak
10. BAVARIAN NORDIC RECEIVES EUROPEAN APPROVAL OF EXTENSION OF VACCINE LABEL TO INCLUDE MONKEYPOX [Internet]. Bavarian Nordic. 2022 [cited 9 August 2022]. Available from: https://www.bavarian-nordic.com/investor/news/news.aspx?news=6595
11. S. GOVERNMENT ORDERS ANOTHER 2.5 MILLION DOSES OF MONKEYPOX VACCINES FROM BAVARIAN NORDIC [Internet]. Bavarian Nordic. 2022 [cited 9 August 2022]. Available from: https://www.bavarian-nordic.com/investor/news/news.aspx?news=6591
12. BAVARIAN NORDIC ENTERS A NEW MULTI-YEAR VACCINE CONTRACT WITH THE GOVERNMENT OF CANADA [Internet]. Bavarian Nordic. 2022 [cited 9 August 2022]. Available from: https://www.bavarian-nordic.com/investor/news/news.aspx?news=6581
13. BAVARIAN NORDIC ENTERS VACCINE SUPPLY CONTRACT WITH THE EUROPEAN HEALTH EMERGENCY PREPAREDNESS AND RESPONSE AUTHORITY (HERA) IN RESPONSE TO MONKEYPOX OUTBREAK [Internet]. Bavarian Nordic. 2022 [cited 9 August 2022]. Available from: https://www.bavarian-nordic.com/investor/news/news.aspx?news=6585
14. BAVARIAN NORDIC SECURES SIGNIFICANT EUROPEAN SMALLPOX/MONKEYPOX VACCINE ORDER FOR 2023 [Internet]. Bavarian Nordic. 2022 [cited 9 August 2022]. Available from: https://www.bavarian-nordic.com/investor/news/news.aspx?news=6593
15. BAVARIAN NORDIC ENTERS ADDITIONAL CONTRACT WITH APAC COUNTRY FOR SUPPLY OF SMALLPOX/MONKEYPOX VACCINE IN 2023 [Internet]. Bavarian Nordic. 2022 [cited 9 August 2022]. Available from: https://www.bavarian-nordic.com/investor/news/news…