By Thomas M. Burton and Peter Loftus
European researchers said Friday that an experimental Ebola
vaccine tested in Guinea "might be effective" in protecting people
from the deadly virus, but behind the scenes, questions have been
raised over the way the study was conducted.
The vaccine, from Merck & Co. and NewLink Genetics Corp. and
dubbed VSV-ZEBOV, is one of a handful of vaccines and drugs that
were rushed into bigger studies after a massive Ebola outbreak hit
West Africa last year. About 27,780 people have been infected and
about 11,290 have died, according to the World Health
Organization.
In the Guinea trial, 4,123 people were assigned to immediate
vaccination, and 3,528 were assigned to delayed vaccination.
The results, published in The Lancet, suggest the vaccine may be
highly effective, with no patients getting sick who immediately got
the vaccine; by contrast, 16 people got sick in the control group
of people who were vaccinated 21 days after exposure.
People familiar with the issue said the U.S. Food and Drug
Administration has prepared a critical commentary about the study,
but that The Lancet, the British journal that is making the study
public online Friday, declined to publish the commentary
simultaneously.
Also, U.S. officials said that the researchers changed the
protocol during the trial--generally a troublesome step--by
deciding to measure cases only after a 10-day cutoff. The European
researchers weren't immediately available to comment.
Mark Feinberg, chief public health and scientific officer for
Merck said, that "the hope was a vaccine might be developed in
sufficient time to have an impact to help control and maybe help
eliminate this Ebola outbreak if it were to persist." He added,
"The study did provide strong evidence supporting vaccine efficacy.
Whether this evidence by itself will be seen by all stakeholders as
definitive will be an important discussion.
The incidence of new cases has waned this year, raising the
prospect that some clinical trials already under way won't provide
definitive results about whether the experimental vaccines and
therapies are safe and effective.
The World Health Organization, working with groups like
England's Wellcome Trust and French group Doctors Without Borders,
started the study in Guinea in March to test whether the VSV-EBOV
vaccine could prevent Ebola.
It was designed as a "ring vaccination" study, in which
researchers identified newly diagnosed Ebola cases. In village A, a
"ring" of people who were in contact with the sick person were
immediately vaccinated. In village B, all such people were
vaccinated but only after 21 days. Village C was immediate, village
D after 21 days, and so on.
The design embodied European researchers' contention that people
shouldn't be randomly assigned to placebo. But U.S. researchers,
with the FDA and National Institutes of Health, contend that only a
"gold-standard" trial with people randomly assigned to vaccine or
placebo could produce the most compelling results.
H. Clifford Lane, deputy director of the NIH's National
Institute of Allergy and Infectious Disease, has said the
ring-vaccination design wasn't ideal because all test subjects get
a vaccine and thus it is difficult to discern differences between
the immediate-vaccine group and the 21-day group.
On Friday, Anthony S. Fauci, director of the NIH's National
Institute of Allergy and Infectious Diseases, called the findings
"very impressive." "It's a complex trial design," he said, "but it
is a step forward." He said it is unlikely the NIH's own study of
the Merck vaccine and of another made by the NIH will move ahead,
largely because "there are almost no cases in Guinea" now.
NewLink, a small biotech company in Ames, Iowa, licensed the
experimental Ebola vaccine from the Public Health Agency of Canada
in 2010.
As last year's Ebola outbreak in West Africa worsened, NewLink
contacted Merck, a major vaccines maker based in Kenilworth, N.J.,
for assistance in putting the vaccine in vials. This led to Merck's
agreement in November to pay $30 million to license rights to the
vaccine and collaborate with NewLink on its development.
Dr. John-Arne Rottingen of the Norwegian Institute of Public
Health, a leading figure in the Guinea study, said researchers in
Guinea stayed away from using a placebo because they feared "that
the outbreak would really continue into an epidemic."
Write to Thomas M. Burton at tom.burton@wsj.com and Peter Loftus
at peter.loftus@wsj.com
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