Takeda’s dengue vaccine achieves Phase III primary endpoint, but key secondary readouts will ultimately determine its fate, says GlobalData

Following Takeda’s announcement on 29 January 2019 that its investigational live-attenuated dengue vaccine, TAK-003, successfully achieved its primary endpoint in the pivotal Phase III TIDES study,

Christopher J. Pace, Director of Infectious Diseases at GlobalData, a leading data and analytics company, offers his view on this development:

‘‘The positive data for TAK-003, which demonstrate the vaccine’s efficacy in protecting children 416 years of age against dengue fever caused by all four clinically relevant dengue virus (DENV) serotypes (DENV-1, DENV-2, DENV-3, and DENV-4), represent a monumental achievement not only for Takeda, but for the dengue vaccine R&D community as a whole. However, they should be treated with cautious optimism, as key secondary readouts expected in six months will play the most important role in determining how TAK-003 stacks up against Sanofi’s first-to-market Dengvaxia, as well as the rest of the dengue vaccine pipeline.

“Specifically, secondary endpoints evaluating vaccine efficacy by serotype, participant baseline serostatus, and disease severity will prove to be the most critical pieces to TAK-003’s clinical and commercial profile, particularly in light of the troubles faced by Dengvaxia, which is associated with more severe cases of dengue infection in DENV-naïve (also known as seronegative) recipients compared with those who were previously exposed to the virus (DENV-experienced).

“In order to be both commercially successful and have a meaningful public health impact on the incidence of dengue in areas where it is endemic, TAK-003 must be equally efficacious against all four DENV serotypes and it must provide strong and durable protection to both DENV-naïve and DENV-experienced individuals.

“Theoretically, TAK-003’s design should enable it to succeed where Dengvaxia floundered. In contrast to Dengvaxia, which possesses a yellow fever virus (YFV) backbone, TAK-003 features an attenuated DENV-2 as the antigenic backbone, exposing recipients’ immune systems to both structural and non-structural DENV proteins—a phenomenon that should induced a stronger, more robust cell-based immunity compared with a YFV-DENV chimera.

“So far, the data obtained from the TAK-003 clinical program support this hypothesis. If the aforementioned secondary endpoints from the TIDES study substantiate past data, it could bring a swift end to the already struggling Dengvaxia’s commercial viability.”

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