New long-term data from Takeda’s TIDES study for its dengue fever vaccine provide the final piece of the puzzle in the Japanese pharma’s quest to bring the first travel shot for the disease to market.
The latest findings build on a previous three-year readout from the same phase 3 trial. Now, the vaccine, dubbed TAK-003, has been shown to be 84% effective at preventing hospitalizations and 61% effective at stopping symptomatic dengue four and a half years after being administered.
TIDES (Tetravalent Immunization against Dengue Efficacy Study) was Takeda’s largest interventional clinical trial to date, enrolling more than 20,000 children and adolescents aged 4 to 16 years across eight dengue-endemic countries to evaluate the safety and efficacy of two doses of TAK-003 in the prevention of laboratory-confirmed symptomatic dengue fever of any severity compared to placebo. This final round of data will be presented June 9 at the Northern European Conference on Travel Medicine.
particles. (CDC/Frederick Murphy)
“What we’ve seen with this latest data is persistence of the protection that we observed at three years at a very high level, especially for hospitalized dengue—that's the most important parameter, at least from a healthcare utilization and a patient perspective,” said Gary Dubin, M.D., president of Takeda’s vaccines business, in an interview with Fierce Biotech.
Takeda has already submitted the latest data to the European Medicines Agency as part of an ongoing approval process for children and adults run in parallel with a swathe of dengue-endemic countries. A decision is expected “later this year,” Dubin said.
“We'll have to let that process play out, but so far it's going well. It's almost a bit unprecedented to have four and a half years of follow-up data available to support licensure of a new vaccine,” he said. “So we're optimistic.”
If a European approval goes ahead and any questions raised by the EU’s Committee for Medicinal Products for Human Use have been addressed, Takeda will turn its attention to the U.S. The submission to the FDA is expected “by the end of this year,” Dubin said.
A wide-open market
The sole dengue vaccine currently on the market, Sanofi’s Dengvaxia, is only approved for people with prior infection. Dengvaxia has faced a bumpy ride since its rollout in 2016, with its use severely curtailed after the discovery that the vaccine can cause more serious dengue cases if given to people who haven’t been infected before. A tricky aspect of the disease is that infection by one of the four serotypes of dengue found worldwide only provides lifelong immunity against that serotype, with later exposure to any of the other serotypes associated with an increased risk of severe disease.
It’s not an issue that TAK-003 has to worry about, however. As with previous data drops from the trial, TAK-003’s effectiveness in the latest findings varied across the four serotypes, but only in a range from “the highest level of protection we’ve seen” against serotype two to “somewhat lower but still substantial protection” against types three and four, Dubin said.
With over half of the world’s population at risk of the mosquito-borne viral disease each year, and the prospect of bringing the first dengue travel vaccine to market, Takeda is currently facing an open goal.
“We would hope that if we're licensed with the broad indication, this would support travel use,” Dubin said. “That is certainly one of our intended targets.”
While Dubin was tight-lipped about Takeda’s commercial expectations for the vaccine, he was enthusiastic about its potential.
“We really do think that there could be significant use of the vaccine in endemic countries, for obvious reasons, but also in people traveling to endemic countries because no one wants to run the risk of experiencing dengue when they're on holiday or returning from holiday,” he said. “It can be at best a very bothersome disease and at worst a life-threatening disease.”
With the main focus of the TIDES trial finally complete, Takeda will now be monitoring the effectiveness of a single booster shot over two years.
“There's no indication that a booster is needed, because at the end of the 54 months we saw maintenance of a high level of protection against hospitalization. In fact, in the last 18 months of the trial, the efficacy against hospitalization was just about as good as it was in the earlier part of the trial,” Dubin said.
“But we did want to … take the opportunity of the trial to see if we could boost responses in the event that a booster ultimately might be needed.”