There is no mpox vaccine available in the Democratic Republic of Congo, the epicenter of a global health emergency declared last week. This is despite the country first requesting shots two years ago and manufacturers saying they have supplies.
“The most important thing we need right now is a vaccine,” said Dr. Samuel Roger Kamba, Congo’s Minister of Health.
So where are the shots? They are trapped in the World Health Organization’s byzantine drug regulatory processes.
Three years after the last global outbreak of mpox, the WHO has yet to formally approve a vaccine (although the US and Europe have) and there is an urgent need to speed up access. No license has been issued.
One of these two approvals is needed for UNICEF and Gavi, an organization that helps promote immunization in developing countries, to purchase and distribute the mpox vaccine in low-income countries like Congo.
While high-income countries rely on their own drug regulatory authorities such as the US Food and Drug Administration, many low- and middle-income countries rely on the WHO to determine which vaccines and treatments are safe and effective. dependent. Pre-qualification.
But Blair Haynewall, a global health consultant who managed the WHO’s approvals portfolio as deputy director of the Bill & Melinda Organization, said the organization was painfully risk-averse and concerned about the need to protect its credibility. He said the country is not prepared to act quickly in an emergency situation. The Gates Foundation has been a major funder for more than a decade.
“They don’t have the flexibility to take a different approach,” she says.
More than 15,000 people have been infected with mpox and at least 550 have died in Congo this year, but many cases remain undiagnosed and untreated. Most of those deaths occur among children, some of whom starve to death after painful lesions in their mouths and throats make them unable to eat.
The WHO declared a global health emergency on August 14 after a new variant of the virus, which spreads through close contact, crossed Congo’s eastern border and entered 13 countries.
Paul Chaplin, CEO of Bavarian Nordic, which makes the Zinneos vaccine that was widely used in North America and Europe during the 2022 mpox outbreak, said the company has 350,000 shots of vaccine ready for sale. He said there is.
He said the company could produce another 10 million doses by the end of 2025, but there are no orders. This week, under pressure from member states, the WHO notified Gabi to begin purchase negotiations with Bavarian Nordic, even though approval of the vaccine is still pending.
The WHO says it was bound by the rules until this unusual step was taken. That means they don’t have the data needed to conduct a full review of Jynneos for approval, and the emergency authorization process can only take place once the public health situation is confirmed. A State of Emergency of International Concern (known as PHEIC) has just occurred.
However, Chaplin said the northern European state of Bavaria first met with the WHO in August 2022 to discuss Ginneos and submitted an information document on the vaccine in May 2023.
The document included data from the study that led to European Medicines Agency approval several years ago, as well as studies conducted since the vaccine was introduced during the mpox outbreak in 2022.
At the time, more than 1.2 million people in the United States had received at least one dose of the vaccine, which studies showed provided a high level of protection against MPX.
However, the WHO did not begin a formal review of the study until last week.
Deusdedit Mbangizi, director of health products policy and standards at WHO, said the agency’s expert group would meet the week of September 16 to consider the data submitted and, if satisfied, issue a new report that week. may also issue permits.
In recent weeks, key infectious disease control officials have increasingly criticized the WHO for unnecessarily slowing efforts to supply vaccines to Africa. A US scientist on a WHO advisory committee but not authorized to speak publicly said it was a “broken system” and “not built for emergencies.” .
Critics have questioned why the WHO did not act sooner to approve the mpox vaccine, even though the virus continues to spread in Congo. And they ask why the vaccination could not be given emergency authorization based on the U.S. and European authorizations of the Ginneos vaccine.
This vaccine was originally created to prevent smallpox and was kept in biosecurity stockpiles even after smallpox was eradicated. Because mpox, like smallpox, is part of the Orthopoxviridae family, researchers wondered if the smallpox vaccine might be effective in blocking mpox. A small study in animals showed its effectiveness.
Although there were no human trials, drug regulators in high-income countries quickly authorized emergency use as mpox began to spread in Europe, North and South America in 2022.
But Mbangizi said it was impossible for the WHO to approve a vaccine at the time. “We were unable to pre-qualify” its effectiveness against mpox “because we didn’t have the data to support it,” he said.
And the WHO decided at the time not to issue an emergency authorization because it wanted to ensure research data was generated, he said. If we allow widespread use, researchers will miss out on that important opportunity.
Then, as the spread of the virus slowed or ended everywhere except Congo, the focus on vaccines disappeared.
This year, as the number of infections in Congo increased, the WHO decided to start an emergency authorization process while declaring a global state of emergency. “We immediately contacted the manufacturer and told them to submit a formal application,” Mbangizi said.
KM Biologics, the Japanese pharmaceutical company that produces the mpox vaccine called LC16, filed the document on Friday. He said Bavarian Nordic had provided additional information on what the WHO called “programmatic suitability for use”.
This refers to aspects of a vaccine that can impact how the vaccine is used in different settings. For example, the Zinneos vaccine must be stored at -20 degrees Celsius, but not all health centers in countries like Congo can store its vials that cold. Regulatory authorities in high-income countries typically do not evaluate vaccines with such considerations in mind.
Most of the data collected on the Jynneos vaccine evaluated its use against clade 2 mpox viruses, the less lethal version that caused the 2022 pandemic. However, the clade 1 virus is endemic in Congo and throughout East Africa, and no vaccines have been tested against it.
“We don’t know if the potency of clade 2 can transfer to clade 1. Nobody has that information,” Mbangizi said.
Congo’s medicines regulator approved the Ginneos and LC16 vaccines on June 27. This was long after Nigeria, which had many mpox cases in the 2022 outbreak, independently approved it.
The long delays have raised eyebrows among health agencies supporting Congo, but Health Minister Dr. Kamba said the country has limited resources and many crises.
“We have many emergencies ahead of us,” Dr. Kamba said.
Congo is currently experiencing outbreaks of measles and cholera, as well as a severe malaria problem that threatens young children. Hundreds of thousands of people displaced by the ongoing armed conflict live in camps.
Now that Congo has approved the vaccine, the country can receive donations — 215,000 doses of Zineos will be shipped to Congo in the coming weeks, Dr. Kamba said.
The European Union has donated 175,000 doses of the vaccine, with a further 40,000 doses coming from the northern European state of Bavaria. The U.S. government has pledged to donate 50,000 doses of Zinneos from the national stockpile.
Congo could simply purchase the mpox vaccine. However, the Japanese vaccine is complicated to administer, requiring rare and special needles, and the Danish vaccine is expensive. In 2022, Bavarian Nordic was selling it for about $110 per dose. Two doses are required for complete vaccination.
As a low-income country, Congo is eligible for support from Gabi, which has a $500 million pandemic emergency response fund set aside for situations like this.
Chaplin declined to say how much Bayern Nordic planned to offer Gavi. “There’s room for adjustment, but it’s based on volume and effort,” he said.
“If the international community said, ‘We want to start vaccinating children in Africa, so we’re going to buy X number of doses per year,’ everything would change,” he added.
With initiatives like this, Chaplin said it would be worthwhile for the company to work with contract manufacturers based in Africa. The company will produce the vaccine at a much lower price while paying royalties to the northern European state of Bavaria.
However, Gabi was waiting for emergency permission from the WHO to start the process.
“Our first priority is to get each country the donated vaccines that we know are available,” said Dr. Derrick Sim, managing director of vaccine markets and health security at Gavi.
Referring to the global health emergency, he said: “When it comes to direct procurement of vaccines, since the PHEIC was announced last week, we have stepped up our efforts, communicating with manufacturers almost daily.” . “As soon as we have a clear picture on demand, we are ready to go.”
Some experts are now wondering why Gabi has to wait for WHO’s vaccine approval.
“If the Gavi board wanted to act quickly in an emergency, it would not be difficult to change it,” said a U.S. global health official who was not authorized to speak publicly on the issue. .
There is already a process in place for WHO to prequalify medicines without fully reviewing the research. Based on FDA reviews, the organization has approved more than 100 drugs, primarily antiviral drugs for the treatment of HIV, for use in the U.S. government’s HIV treatment program Pepfer in African countries.
There are reasons to be careful. Dr. Placido Mbala, director of the Clinical Research Center at the Kinshasa National Institute of Biomedical Research, said he is hopeful about the vaccine, but it remains to be seen how effective it will be against the variant of the virus currently circulating in Congo. He said it was a matter of resolution. .
Dr. Mbala was co-principal investigator in a large U.S.-funded trial of tecobilimat, an antiviral drug used to treat mpox, in high-income countries in 2022. Last week, the National Institute of Allergy and Infectious Diseases announced: This drug did not improve mpox resolution in Congolese patients with clade 1 infections.
“Drugs and vaccines can work differently in different situations, as we saw with Tecobilimat,” Dr. Mbala said. “We can’t be sure until we can test it.”
