Takeda's dengue vaccine effective overall in study but with major limitation

By Julie Steenhuysen
CHICAGO, Nov 6 (Reuters) - Takeda Pharmaceutical Co's
4502.T experimental dengue vaccine was highly effective at
preventing the mosquito-borne disease in a late stage study, but
it failed to protect against one type of the virus in people
with no prior exposure to dengue.
Takeda's vaccine was 80.2% effective at preventing dengue
among children and teens in the year after they got the shot,
according to results of a Phase III study published in the New
England Journal of Medicine on Wednesday.
Sanofi's SASY.PA Dengvaxia - the world's first dengue
vaccine - had demonstrated 59.2% overall efficacy in the first
year of follow-up based on combined results from two late stage
trials.
A preliminary analysis of Takeda vaccine's performance
suggests it may offer unbalanced protection among the four types
of dengue, which could increase risks of severe disease in
people never previously infected with dengue.
The results follow Sanofi's 2017 disclosure that Dengvaxia
increased the risk of severe dengue in children who had no prior
dengue exposure when they got the shot.
That news triggered a government investigation in the
Philippines where 800,000 school-age children had already been
vaccinated. Fallout from Sanofi's vaccine has raised the bar for
demonstrating the safety of future dengue vaccines.
Experts have long been concerned that a dengue vaccine that
is only partially protective could increase the risk of severe
disease after exposure to a second type of the virus.
Among roughly a quarter of study subjects with no prior
dengue exposure who got Takeda's vaccine, the shot was 75%
percent effective at preventing all four types of dengue.
"This is a fantastic result and we're thrilled," Derek
Wallace, who runs Takeda's global dengue vaccine program, said
in a phone interview, noting that the results were similar
between those who have and have not had dengue before.
There is an urgent need for an effective dengue vaccine. The
tropical disease infects nearly 400 million people a year and
kills up to 25,000 people.
Much of the vaccine's overall benefit, however, appeared in
people infected with dengue 2, the type of dengue that forms the
basis of the vaccine known as TAK-003. It was 97.7% effective at
preventing dengue 2, but lead researchers said the effect was
"modest" against the other three types of the virus.
There was no difference in effectiveness against dengue 2
among those with no prior exposure to dengue and those
previously exposed, and a slightly lower benefit against dengue
1 for those with no prior exposure.
But preliminary evidence suggests the vaccine failed to
protect against dengue 3 in children and teens with no prior
dengue exposure, and there was not enough evidence to make a
call about its effect on dengue 4, researchers said.
"Overall, the results are encouraging," said Dr. Anna
Durbin, a dengue researcher at the Johns Hopkins Bloomberg
School of Public Health who was not involved in the study.
"There may be an imbalance in the vaccine, particularly with
dengue 3 and maybe dengue 4, but the efficacy was very good,"
said Durbin, who helped develop a rival dengue vaccine with the
U.S. National Institutes of Health that is in late stage testing
in Brazil.
Dr. In-Kyu Yoon, director of the Global Dengue &
Aedes-Transmitted Diseases Consortium, who has been a paid
adviser to Takeda, called the findings mixed and said more
follow-up is needed.
Takeda said it plans to file for approval in countries with
the biggest dengue burden, with the first submission expected in
the second half of 2020. Takeda will release additional data at a medical conference
later this month.