Takeda Highlights Data from Clinical Trial of Investigational Norovirus Vaccine Candidate
Takeda Pharmaceutical Company Limited (Takeda) announced today results
of a Phase 1/2 study of its intramuscular bivalent (GI/GII) norovirus
vaccine candidate in healthy adult volunteers who were challenged with
the most commonly occurring norovirus (genotype GII.4) that causes
gastroenteritis. The study demonstrated that two doses of the
experimental bivalent norovirus were well tolerated, and that the
candidate vaccine had a clinically relevant impact on the incidence of
norovirus illness after challenge, as well as the severity in
breakthrough cases. In addition to the impact on clinical illness, a
positive trend toward reduction in viral shedding in stool was observed.
The study also provided important information toward optimization of
confirmatory lab testing for norovirus disease and infection in a future
field trial. The data from that study were highlighted today at an
IDWeek 2013-sponsored press conference in San Francisco and will be
presented tomorrow as a late-breaking oral presentation at the
Norovirus gastroenteritis is most commonly associated with vomiting and
diarrhea, and occurs in all age groups. In the study, a statistically
significant reduction in mild, moderate or severe vomiting and/or
diarrhea was observed in vaccinated subjects, meeting the secondary
endpoint of the study. The total number of subjects with gastroenteritis
symptoms was also reduced in the vaccine group, but this reduction was
not statistically significant and the primary endpoint was not met.
“Norovirus causes nearly 90 percent of epidemic non-bacterial outbreaks
of gastroenteritis around the world, leading to as many as 71,000
hospitalizations each year in the U.S. alone,” said the study’s lead
investigator David I. Bernstein, M.D., M.A. and director of Infectious
Diseases at Cincinnati Children’s Hospital. “There is a critical unmet
medical need for a vaccine to combat this significant global health
issue, and this vaccine candidate has the potential to address that
“This is the first time that vaccination with a norovirus candidate
vaccine has resulted in a reduction of symptoms caused by experimental
exposure to the most common strain of norovirus, genotype GII.4. We are
very encouraged by these findings, from one of the largest human
challenge studies performed to date, which pave the way for further
development of this first-in-class vaccine,” said Rajeev Venkayya, M.D.,
executive vice president and head of Takeda’s Vaccine Business Division.
“The research and development of innovative vaccines like our norovirus
candidate reflect Takeda’s commitment to addressing the most important
challenges in global public health.”
Results from the Phase 1/2 randomized, double blind, placebo-controlled
multi-center study of 98 healthy adults, age 18-50 were:
There were no cases of severe vomiting and/or diarrhea in the vaccine
group versus four in the placebo group following challenge with live
norovirus (0.0% vs. 8.3%; p=0.054).
Although there were numerical reductions (68%) in moderate or severe
vomiting or diarrhea, these did not reach statistical significance
(6.0% vs. 18.8%; p=0.068).
A secondary endpoint was met, with a 52 percent reduction against
vomiting and/or diarrhea of any severity (20% of people who received
the vaccine vs. 41.7% of those who received placebo; p=0.028).
In those who experienced illness symptoms, severity of illness as
measured by the Vesikari scoring system (modified for use in adults)
was significantly reduced in vaccinees vs. placebo recipients (mean
severity score of 3.1 vs. 5.0, p=0.023).
Side effects were mostly mild and of limited duration, with pain at
the injection site being the most common local reaction, similar to
other vaccines. The most common systemic reaction was headache.
A 4-fold increase in antibody titer was an inadequate measure of
disease, as titers in vaccinees showed only a minor increase after
challenge. PCR positivity did not differentiate between infection and
The primary composite endpoint of this study, the reduction of
incidence of acute gastroenteritis of any severity and laboratory
ascertainment for norovirus, was not met as per above. A manuscript
detailing the study will be submitted for publication.
About Takeda’s Norovirus Vaccine Candidate
Takeda’s intramuscular bivalent norovirus vaccine contains virus-like
particle (VLP) antigens resembling the virus while lacking the ability
to reproduce or cause illness. VLPs mimic the natural virus by
preserving the authentic structure of the viral capsid, the shell of
protein that protects the nucleic acid of a virus. The human immune
system has been shown to respond to a VLP vaccine similar to
encountering the live virus, allowing the body to build immune defenses
capable of fighting infections. Without genetic material, VLP vaccines
are incapable of causing infections themselves.
In a previous challenge study with a vaccine formulated for nasal
administration, results showed a significant reduction in
gastrointestinal illness in volunteers who were challenged with genotype
I.1 norovirus. These results were published in The New England Journal
of Medicine on December 8, 2011. Collectively, the two challenge studies
indicate that vaccination may be a useful tool to prevent disease caused
by both genogroup I and genogroup II noroviruses, the two genogroups
that are most commonly associated with norovirus infection in humans.
Norovirus gastroenteritis is a widespread and potentially severe illness
characterized by the acute onset of nausea, vomiting, abdominal cramps,
diarrhea and occasionally fever. Noroviruses are highly infective and
easily transmitted from person to person or via contaminated
environments. Epidemic outbreaks occur in community environments,
particularly hospitals, hotels, schools, day care facilities and nursing
homes, with mounting socioeconomic cost to families, the health care
system and businesses. Military units are significantly affected when
the virus strikes, as outbreaks impact combat readiness. Severe clinical
outcomes are reported in older adults, children and immunocompromised
individuals in whom infection can lead to substantial complications and
can even lead to death.
Takeda’s Vaccine Business Division
Takeda has a proven track record of manufacturing and supplying vaccines
in Japan for more than sixty years. Takeda’s global vaccine business
division was launched in January 2012 to build upon this success, and is
headquartered in Deerfield, Illinois. The company acquired LigoCyte
Pharmaceuticals and its norovirus vaccine candidate, as well as its
proprietary virus like particle vaccine platform and several preclinical
vaccine candidates in October 2012. In May 2013, Takeda acquired
Inviragen, Inc., and its viral vaccines candidates for emerging
infectious diseases, including dengue and hand, foot and mouth disease
About Takeda Pharmaceutical Company Limited
Located in Osaka, Japan, Takeda is a research-based global company with
its main focus on pharmaceuticals. As the largest pharmaceutical company
in Japan and one of the global leaders of the industry, Takeda is
committed to strive towards better health for people worldwide through
leading innovation in medicine. Additional information about Takeda is
available through its corporate website, www.takeda.com.
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Copyright Business Wire 2013