Impressive interim phase III results achieved by Merck & Co and NewLink Genetics' vaccine against Ebola position it to be the first such product approved for the disease. But with the current epidemic in West Africa subsiding the development might have come too late to make any real difference, for now.
The product could at least be useful in the future. “The vaccine would still be critical to intervene in future outbreaks and to vaccinate frontline workers in countries at risk,” said Marie-Paule Kieny, assistant director-general of the WHO, and one of the researchers involved in the study in Guinea.
“The current status of the epidemic does not suggest that widespread vaccination should be considered at this moment," she told EP Vantage. "Indeed, there are very few new cases and most populations in West Africa are not at immediate risk.”
This makes it unlikely that the prophylactic vaccine, rVSV-ZEBOV, will receive emergency use authorisation, she believes.
But Merck is pushing ahead with efforts to get regulatory approval from the FDA and EMA. This could take a year or two, estimates Dr Mark Feinberg, Merck Vaccines’ chief public health and science officer.
He told EP Vantage: “It’s almost certain that there will be future Ebola outbreaks, and we need to be better prepared than we were for this most recent one.”
The phase III trial published in The Lancet found 100% efficacy when rVSV-ZEBOV was used in a ring vaccination strategy – whereby contacts of a patient with Ebola, as well as the contacts' contacts, are vaccinated.
The study tested immediate vaccination of these “rings” versus delayed vaccination, 21 days later. There were no Ebola cases in the 4,100 people in the immediate vaccination group after 10 days, but there were 16 in the delayed vaccination group, which included around 3,500 people.
Ms Kieny cautioned that the 100% efficacy rate was unlikely to be maintained with broader use. “In all vaccines there is what is called vaccine breakthrough, where eventually one person has not been protected. But, so far, we have not had any of those cases.”
There have been criticisms of the ring vaccination design, with some saying that a conventional placebo-controlled study might be more valid, but Dr Feinberg contended that “the design of the study was relevant”. There are also ethical concerns with randomising people to placebo in a disease as deadly as Ebola.
The study in Guinea is ongoing, but has now moved on to vaccinating all participants immediately. The vaccine is also being tested in Liberia and Sierra Leone, the other worst-hit countries in the Ebola crisis.
The Prevail study in Liberia, which in addition to rVSV-ZEBOV is also testing GlaxoSmithKline’s candidate cAd3-EBOZ, includes a placebo group. In March, both vaccines were shown to be safe in the phase II portion of the study, clearing the way for the phase III part of the trial to begin.
Meanwhile the Strive trial in Sierra Leone employs a similar strategy to the Guinea study, comparing immediate with deferred vaccination.
rVSV-ZEBOV, originally engineered by the Public Health Agency of Canada and licensed to NewLink before being picked up by Merck, is the most advanced Ebola vaccine in development, and the only one for which efficacy results are available, according to Ms Kieny.
Others being studied include GlaxoSmithKline’s cAd3-EBOZ, co-developed with the US National Institute of Allergy and Infectious Diseases, and a combination vaccine being developed by Johnson & Johnson and Bavarian Nordic under a deal signed last year (Bavarian Nordic leaps ahead in Ebola race, October 22, 2014).
Ms Kieny has worked with GSK and J&J on their candidates, which she described as “also very promising”.
But they are further behind. GSK’s vaccine, as previously mentioned, has passed muster in phase II in the Prevail study in Liberia, while J&J/Bavarian Nordic’s contender started a phase II trial in July. Also last month, Novavax reported topline results from a phase I study of its vaccine.
If all goes smoothly Merck should be the first to get an Ebola vaccine approved, potentially giving it the edge over its rivals. But Dr Feinberg is adamant that the company is not in it for the money: “We didn’t view this as a commercial programme – our primary focus [in Ebola] is on delivering a public health good rather than a commercial return.”
He did admit that governments and organisations might be interested in stockpiling a vaccine for possible future outbreaks. “Exactly how much that would be is still being explored with external stakeholders,” he said. The company declined to give any sales forecasts for the Ebola vaccine.
The question of who will pay for a vaccine is also pertinent – will it be kept in reserve by wealthier countries in case a new outbreak makes it to their shores, or will it be distributed to the areas already affected?
Another worry is that new strains of Ebola could render the current vaccine useless.
This should not be as big a problem as it is with flu, for example, as there is not much genetic variation within an Ebola species, Dr Feinberg explained. However, different Ebola species could each require a different vaccine, he added.
As well as the vaccine for the current outbreak, caused by the Zaire Ebola strain, Merck is already working on possible candidates for other Ebola species and related filoviruses.
Dr Feinberg concluded: “One of the lessons from this outbreak is that you need to be prepared in advance. While a lot has been accomplished in a short amount of time, it would have been better if we’d had this tool at the beginning.”
|Company||Vaccine||Status||Ongoing studies||Trial ID|
|Merck/NewLink Genetics||rVSV-ZEBOV||Phase III interim results from Guinea trial reported||Ebola ça suffit (phase III, Guinea); Strive (phase III, Sierra Leone); Prevail (phase II/III, Liberia)||NCT02378753; NCT02344407|
|J&J/Bavarian Nordic||Ad26.ZEBOV plus MVA-BN Filo||Phase II||Study of three prime-boost regimens||NCT02416453|
|Novavax||Ebola GP vaccine||Phase I||Ebola GP Vaccine clinical trial||NCT02370589|