New data from two clinical trials continue to support the efficacy and safety of Takeda's live attenuated tetravalent dengue-vaccine candidate TAK-003. Both studies involved children and adolescents living in dengue-endemic areas. "Overall, the 18-month data reported from our phase 3 Tetravalent Immunization against Dengue Efficacy Study (TIDES) trial and the 48-month data from our phase 2 DEN-204 trial are consistent with previously reported safety, immunogenicity and efficacy data of TAK-003," Derek Wallace, who heads Takeda's global dengue program, told Reuters Health by email. "With this additional data we are gaining greater insight into the potential benefit of our dengue vaccine candidate," he said. In the phase-2 DEN-204 trial, 1,800 children aged 2 to 17 years were randomly allocated to one of four treatment arms: a two-dose primary series (day one and day 91) of TAK-003, one primary dose, one primary dose plus one-year booster, or placebo. A total of 1,479 children, or 82%, completed the 48-month study at three sites in the Dominican Republic, Panama and the Philippines. TAK-003 elicited antibody responses against all four serotypes, which persisted to 48 months after vaccination, regardless of baseline serostatus, Wallace and colleagues report in The Lancet. "No important safety risks were identified during the study, during which we observed a lower incidence of virologically confirmed dengue in vaccine recipients than placebo recipients, indicating a protective effect of TAK-003 against dengue in line with recent efficacy data from the pivotal phase 3 study," they write. "The final 48-month results from DEN-204 described long-term safety, demonstrated the durability of immune response of TAK-003," Wallace added in email to Reuters Health. The DEN-204 results support the two-dose primary series used in the ongoing phase 3 TIDES study. In this study, also published in The Lancet, more than 20,000 healthy children aged 4 to 16 years from Asia and Latin America were randomly allocated to receive the two-dose schedule of TAK-003 or placebo. "The primary endpoint was achieved with an overall vaccine efficacy of 80.2%," Wallace and colleagues report. There were fewer virologically confirmed dengue cases in the vaccine group than in the placebo group (61 vs. 149). Vaccine efficacy was 66.2% in people seronegative at baseline and 76.1% in those who were seropositive at the outset. TAK-003 reduced the number of dengue cases requiring hospital stay by 90.4% and dengue hemorrhagic fever by 85.9%, and had an acceptable safety profile, with no vaccine-related serious side effects or severe dengue virus disease reported. "We observed generally consistent trends in the 18-month analysis of the TIDES trial as compared to the 12-month primary endpoint analysis including overall efficacy, efficacy among people not previously exposed to dengue (seronegative), and in safety," Wallace told Reuters Health. "The TIDES trial met all secondary endpoints for which there were a sufficient number of cases." The TIDES trial is ongoing and safety and efficacy will be assessed over a total of four and a half years. Takeda plans to share 24-month data from the trial later this year. Writing in a Lancet Comment, Dr. Annelies Wilder-Smith with the London School of Hygiene and Tropical Medicine says the "encouraging key messages include that TAK-003 can be used both in individuals who are seropositive and seronegative. The high efficacy of 90.4% against hospitalized dengue underpins that TAK-003 can potentially serve as an impactful public health tool in reducing the dengue burden on healthcare systems." "TAK-003 could also be of potential use as a vaccine for international travelers, given that dengue has become a leading cause of febrile illness in travelers to dengue-endemic countries. However, some complex nuances for serotypes 3 and 4 will require extended follow-up, and careful balancing by regulators and public health officials in determining the potential utility and safety of this vaccine," she concludes. Both studies were funded by Takeda Vaccines, which employs several authors on the studies. —Megan Brooks Source
