Merck to make more Ebola vaccine, WHO declines to declare global emergency

MANILA — Merck announced it would produce an estimated 450,000 additional doses of experimental Ebola vaccine, just after the first cross-border case was confirmed to have spread to Uganda from the Democratic Republic of Congo. But the World Health Organization declined on Friday to declare the outbreak a global emergency.

“Merck has determined with the U.S. Government, WHO and others that additional vaccine supply would benefit overall public health preparedness — both, to support the current DRC outbreak and preparedness against any new Ebola ... outbreak(s) that might occur,” Pamela Eisele, product, pipeline, and supply media relations at Merck, told Devex in an email, just days after the first case of Ebola was reported in Uganda. Eisele said the decision was made “recently.”

Just last week, U.S. Centers for Disease Control and Prevention Director Robert Redfield raised concerns that responders may run out of the investigational Ebola vaccine, currently the only one used in the DRC response outbreak.

“Unfortunately, there’s going to be a six to 12-month lag before there’s adequate vaccine supply, so we do project that we are going to run out of vaccine,” he said in testimony before the U.S. House of Representatives.

Mike Ryan, head of WHO’s health emergencies program, said in a press conference on Friday that there are “a quarter of a million doses” of Ebola experimental vaccines ready to ship, and a further 100,000 doses by the end of the year. While adjustments on vaccine dose usage has been made to double its reach, WHO welcomes Merck’s decision to produce more from its plant in West Point, Pennsylvania.

To aid Uganda in its response, meanwhile, WHO flew in 4,000 doses of the vaccine, and the DRC health ministry donated 400 doses of its own stock to the country, according to a news release issued on Thursday by Uganda Minister of Health Jane Aceng.

Merck declined to provide specific numbers of its current stockpile.

“We do not give out specific numbers at any given point in time, because it fluctuates. The stockpile, as with any vaccine stockpile, is inherently dynamic — numbers change due to shipments, expiry, and replenishment,” Eisele said.

But she said that in addition to the currently available supply, Merck would produce an estimated 450,000 additional doses of investigational V920 that should be available “in about 12 +/- months.”

“This new supply is intended to help offer continuity in preparedness, inform future planning by WHO and others, and serve as a bridge until V920 is licensed and our manufacturing facility is operational and producing commercially-labeled doses,” she added.

The company is still waiting for validation to operate its German facility where it expected to continue production of the vaccine. Getting the facility up and running remains a top priority for the company so it can have a “more sustainable supply” of the vaccine,” Eisele said.

Outbreak spreads, but not a global emergency

The decision to produce additional doses of the vaccine comes amid worrying developments in the outbreak. On June 11, Uganda confirmed the first cross-border case of Ebola in the country — a 5-year-old Congolese child who was traveling with his family. They entered Uganda through Bwera, and sought medical help at Kagando hospital. The child was later transferred to the Ebola treatment unit in Bwera, after the Uganda Virus Research Institute confirmed the case as Ebola. The child died on Wednesday, followed by his 50-year-old grandmother, who died on Thursday.

The rest of the family has been repatriated to DRC, including the boy’s 3-year-old brother, who is confirmed to have Ebola. WHO’s Ryan said the child was returned to the DRC so he could receive the necessary treatment. While the Ugandan government has made almost a yearlong effort to prepare for Ebola, it has not gone through the process yet of approving investigational therapeutics, or the Monitored Emergency Use of Unregistered and Investigational Interventions for Ebola Virus Disease (MEURI) protocol, as part of treatment interventions in Ebola cases.

The MEURI protocol is an ethical framework developed by WHO establishing the criteria to be met to allow patient access to investigational therapeutics outside of clinical trials.

The International Health Regulations Emergency Committee on Friday recommended countries put in place the necessary approvals for investigational therapeutics as part of their preparedness measures. The committee, which was reconvened by WHO Director-General Tedros Adhanom Ghebreyesus to review the Ebola outbreak, also recommended vaccine strategies that have “maximum impact on curtailing the outbreak … be implemented rapidly.”

But for the third time since the outbreak was declared in August 2018, the committee advised against declaring it as a global emergency. While it viewed the outbreak as a health emergency in DRC and the region, acting committee chair Dr. Preben Aavitsland said it “does not meet all the three criteria for a public health emergency of international concern under the IHR.”

“While the outbreak is an extraordinary event and there is a risk of international spread, we believe that the ongoing response would not be enhanced by formal temporary recommendations from WHO under the International Health Regulations,” he said.

Aavitsland said there was extensive debate over the impact of a PHEIC declaration on the response and that different views were expressed during the meeting, which lasted an hour longer than it was scheduled. He would not give many details of the discussions and would not reveal whether the decision not to declare a PHEIC was unanimous.

“The committee consists of members of different backgrounds [and] different expertise, and in the group, many views were represented and expressed, and we had a long and substantial discussion after [the] presentation of all the facts. In the end, we do not take votes. We draft a statement and we agreed collectively on the statement,” he said.

He said declaring the outbreak as a PHEIC would allow WHO to share information about the disease spread even if affected countries were against it, and to provide temporary recommendations to member states that they have to follow. But both, he said, are not needed, as DRC and Uganda are already “extremely transparent” about their situations, and that both countries and others are already following WHO’s advice.

Declaring a PHEIC could have some risks, including restrictions on travel and trade, and border closures, which could severely harm the DRC’s economy.

“So it was the view of the committee that there is really nothing to gain by declaring a PHEIC, but there is potentially a lot to lose,” he said.

In addition, he said declaring a PHEIC to raise additional funds for the response “would be a misuse of the instrument.” The fact that people, including children and responders, are dying in this outbreak should be reason enough for donors to fund the response, he said.

Others in the global health community questioned the decision.

"It is surprising how the Emergency Committee reached its conclusion,” said Alexandra Phelan, a global health legal and policy expert who has consulted for WHO and is currently a faculty member at Georgetown’s Center for Global Health Science and Security.

She said the third criterion of PHEIC, which is an event requiring immediate international action, has been met by repeated calls for international financial, technical, and political support for preparedness and response efforts.

"The Emergency Committee’s statement that desperate financial support is needed and that temporary recommendations would not be useful raises a key question: what then is the purpose of a PHEIC? Today’s decision indicates that the laws governing international health emergencies may no longer be appropriately tailored for complex situations like this outbreak or are no longer being used as they were once envisioned,” she said.

"While controlling this outbreak is the most important focus right now, in the medium term the WHO and countries should examine what revisions may be required — such as establishing an intermediate level declaration for public health emergencies of regional concern — so that we can mobilize funding, assistance, and recommendations rapidly for future outbreaks,” she added.

There have been over 2,000 confirmed Ebola cases in DRC since the outbreak was declared in August 2018, including 1,420 deaths, as of the June 13 update by the Ministry of Health. In Uganda, meanwhile, the government has identified 98 contacts that may have been exposed to the infected individuals, with 10 considered “high risk,” said WHO’s Ryan.