Longer-term data fail to clear concern over Takeda's dengue vaccine

By Julie Steenhuysen

CHICAGO (Reuters) - An additional six months of data from a late-stage trial of Takeda Pharmaceutical Co's experimental dengue vaccine again showed it failed to protect against one of the four types of the virus in an important patient group, researchers said on Saturday.

The longer-term data, presented at the American Society of Tropical Medicine and Hygiene meeting in Maryland, also showed a slight waning of the overall effectiveness of the vaccine, TAK-003.

At 12 months after a second dose, the vaccine was deemed 80.2% effective. Six months later is was down to 73.3%.

Initial results, published this month in the New England Journal of Medicine, showed the vaccine succeeded overall but failed to protect against dengue 3 in children and teens who had never previously been exposed to the mosquito-borne disease.

"That is a finding we immediately honed in on when we looked at the data," Dr. Rajeev Venkayya, president of Takeda's global vaccine business, said in a phone interview. "We agree with others, we need more data to fully understand the profile."

Experts have long worried that a dengue vaccine that is not fully protective against all four virus types could increase the risk of severe disease.

That appeared to have happened with Sanofi's Dengvaxia, the world's first dengue vaccine. Two years after Dengvaxia was licensed in 2015, the company disclosed that it increased the risk of severe disease in children not previously infected, a group known as seronegatives.

Takeda's vaccine is based on a dengue 2 virus, with DNA from the other three added in. In the study, the vaccine performed best against dengue 2, proving 95.1% effective.

That helped drive the overall benefit, Venkayya said, adding that dengue 2 accounted for fewer cases in the 18-month data, which may explain the dip in efficacy.

The vaccine proved 90.4% effective at preventing hospitalized dengue and 85.9% effective at preventing hemorrhagic fever.

"The big picture here is the vaccine could be a very valuable tool for public health," Venkayya said. However, he said, "we can't ignore this finding in a subpopulation of seronegatives that are exposed to dengue 3."

So far, there is no sign that Takeda's vaccine increases the risk of severe dengue. "Over time, we hope to gain a better sense of whether that is an issue," he said.

Takeda plans to file for approval in the second half of 2020, and will collect safety data for at least 4-1/2 years Venkayya said.

(Reporting by Julie Steenhuysen; Editing by Bill Berkrot)