DF and DHF are caused by one of four closely related, but antigenically distinct virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4) of the genus Flavivirus. Infection with one of these serotypes provides immunity to only that serotype for life, so persons living in a dengue-endemic area can have more than one dengue infection during their lifetime.
Takeda’s dengue vaccine produces promising results in a trial
Takeda’s dengue candidate TAK-003 has now shown a high protective efficacy rate in the DEN-204 trial, achieving a 71% reduction in the risk of developing symptomatic dengue compared to placebo in children and adolescents.
The DEN-204 trial is an ongoing phase 2 trial in the disease, which threatens up to 40% of the world’s population and is a leading cause of serious illness and death among children.
Dengue is the fastest spreading mosquito-borne viral disease and 40% of the world’s population lives under the threat of the virus, according to the World Health Organization (WHO).
The disease infects 390 million people a year and symptoms include fever, a hammering headache, flu-like symptoms, bone, muscle and joint pain, rash and nausea and vomiting.
While most patients recover, the disease poses a considerable economic burden on society – it is estimated to cost India upwards of $500m a year for example – and causes around 20,000 deaths a year worldwide.
Results demonstrate how TDV was well tolerated and immunogenic against all four dengue serotypes, irrespective of baseline dengue serostatus. These data provide proof of concept for TDV and support the ongoing phase 3 efficacy assessment of two doses 3 months apart.
While Sanofi’s Dengvaxia was the first vaccine approved for dengue, it does not protect equally against the four different strains of the virus in trials.
But 18-month data published in the journal Lancet Infectious Diseases vaccine TAK-003 produced sustained antibody responses against the four strains, regardless of previous exposure and dosing schedule.
Sanofi initially had high hopes for its dengue vaccine, touting it as a potential $1-billion-a-year-plus product, but initial sales last year were only 55 million euros ($64 million) and industry analysts have been dialing back expectations.
Takeda has already completed nine Phase I and Phase II trials for this vaccine, capturing evidence of safety and efficacy. Initial results from the Phase III study will start to roll in next year. Takeda is already getting ready for commercial roll out. The company has invested more than €100 million in a new vaccine plant to manufacture a global supply.
In Phase 2 trials, Takeda’s vaccine improved overall reduction of dengue disease cases by 71.1%, which compares favorably to Sanofi’s Dengvaxia’s results of 60.8%.
The trial showed that 21 individuals (1.3%) of the 1,596 children and adolescents vaccinated with TAK-003 were found to have contracted dengue, against the nine (4.5%) of 198 individuals receiving a placebo.
Beyond this, Takeda’s TAK-003 was able to achieve a sustained antibody response against all four serotypes of the virus – Sanofi managed protection against all four types, but with differing levels of efficacy.
Takeda is currently running a Phase 3 efficacy trial where it will hope to be able to prove that its vaccine can surpass Sanofi across all four serotypes.
“We are seeing an acceptable safety profile and sustained antibody responses out to 18 months in this trial,” said Derek Wallace, who is leading the TAK-003 development programme at Takeda. “The reduced incidence of dengue in children and adolescents receiving TAK-003 is encouraging, however, data from our ongoing Phase 3 efficacy trial, TIDES, are required to confirm these findings.”
