This news release discusses the results of a World Health Organization-led study of an experimental Ebola vaccine manufactured by Merck, Sharpe & Dohme. The study tested the effectiveness of the vaccine (currently referred to as rVSV-ZEBOV) among individuals who had come in contact with people diagnosed with Ebola within three weeks prior to the diagnosis, including contacts of those contacts, using a “ring vaccination” approach similar to that used to fight smallpox in the mid- to late 20th century. Among the 5,837 individuals who were vaccinated immediately after assignment to the study, none developed Ebola 10 days or more after being enrolled. In comparison, there were 23 Ebola cases identified 10 days or more in the group of 4,507 assigned to either a delayed vaccination (16 cases) or no vaccination (7 cases).
The release delivers a good description of harms, is written in a balanced and non-sensational tone, and provides an overview of next steps for the vaccine. The release would have been improved with some reference to cost and the other Ebola vaccines under development by major pharmaceutical competitors.
Health organizations worldwide have been scrambling to develop an effective vaccine against Ebola since the 2013-2016 Ebola outbreak in West Africa which killed more than 11,300 people.
Merck received “Breakthrough Therapy Designation” status in 2016 from the U.S. Food and Drug Administration and “PRIME” status from the European Medicines Agency for this closely watched vaccine. The “breakthrough” and PRIME status speeds up the review process for the vaccine once it is submitted to the U.S. Food and Drug Administration and/or the European Medicines Agency for approval.
The news release provides no information about how much the vaccine is likely to cost. Cost is especially important in the developing world where it is most likely to be used and in large quantities.
The news release explains that, among participants vaccinated immediately, no Ebola cases were identified 10 days or more after vaccination, compared to 23 cases among individuals assigned to the delayed vaccination group. The data also suggested that the vaccine reduced Ebola risks for unvaccinated individuals within the contact rings of those who were vaccinated, but the news release notes that the study was not designed to test this so-called “herd immunity” effect, so it will require further research to confirm that vaccinating some individuals reduces the likelihood of their contacts developing Ebola.
The release could have explained more clearly that the virus has a 10 day incubation period during which the virus can develop in the patient and not be affected by the vaccine as the body won’t have time to develop immunity. But the fact that the two groups (vaccinated and delayed vaccination) had equal numbers during the 0 to 10 day period helps to confirm that the two groups were equal in their exposure to the virus and risk of developing Ebola.
The news release also accurately quantifies the harms associated with this vaccine, noting that more than half of those vaccinated reported mild side effects, including short-term headaches, fatigue and muscle pain. The release also identified two serious negative reactions (a high fever and an allergic reaction) associated with the vaccination and a flu-like illness that might have been a result of the vaccine. This is a particularly strong point of the release in that many releases on drug/vaccine studies don’t quantify the adverse event rates very clearly or completely.
The news release notes that the trials involved 5,837 people who received the vaccine and 6,004 who did not. The fact that no patients in the vaccination group developed Ebola suggests that the vaccine does indeed have some effect. The statistical significance in the two groups for all patients was p = 0.01, suggesting that the result was unlikely to have occurred by chance alone. On the other hand, the fact that the study was stopped early does raise the possibility that a longer lasting study would have found a smaller difference between the two groups as this is typically found in studies stopped early for effect.
Ebola is certainly a serious disease, given the high fatality rates when outbreaks occur. The news release acknowledges this but does not use sensational language or otherwise overplay the risks Ebola poses.
The news release identifies the funding sources for the study, which included WHO and a number of government agencies from Canada, the United Kingdom, Norway, along with the international organizations the Wellcome Trust and Médecins Sans Frontières. The news release also identifies the organizations with which the study’s research team members were associated, although it does not give any indication of the extent to which research team members or their organizations receive additional funding from Merck, which obviously stands to gain the most if the vaccine proves effective and is recommended for use by the World Health Organization.
The news release also briefly summarizes a study of a different Ebola vaccine candidate being developed by a Chinese organization. This study, also published in the same issue of The Lancet, was much smaller, involving only 500 participants, and suggested that the effectiveness of this vaccine declined during the first six months after the initial injection.
To be even more thorough, the release might have acknowledged that still other vaccines are under development by GlaxoSmithKline, Johnson & Johnson and at least one other pharmaceutical company.
The news release provides fairly detailed information about the next steps in the vaccine approval process, noting that Merck has committed to submitting the vaccine for regulatory approval by the end of 2017 and that the company has committed to making 300,000 doses available should an outbreak occur before approval is gained. It also notes that if an outbreak occurred before the vaccine is approved, it could be used, with informed consent of those vaccinated, through a “compassionate use” program.
The news release notes that no other Ebola vaccine is currently available, briefly summarizes results of a trial of an alternative vaccine and notes that the study findings being described “add weight to early trial results” published previously on the same vaccine.
The Lancet news release eschews sensational language in reference to either Ebola or the vaccine. However, the statement that there was a dramatic effect (0 deaths vs 23 deaths) suggests that this is a super vaccine and perhaps too good to be true.