Takeda's Dengue Vaccine Still Promising, But Could Be A Niche Market
Executive Summary
Long-term Phase II data have backed Takeda's drive to study its dengue vaccine in Phase III, but to grow the market the company may have to reverse the reluctance of countries to fund public vaccination campaigns.
Takeda Pharmaceutical Co. Ltd. lists three research areas – GI, oncology and CNS – from which it wants to grow a more specialty-based business, but the Tokyo, Japan-based business also remains active in researching novel vaccines, including a potential dengue vaccine, TAK-003, for which it has just released an interim 18-month analysis of Phase II data that backed the start of the Phase III TIDES study in September 2016.
Importantly, Takeda reports that children receiving TAK-003 in dengue-endemic areas in the Dominican Republic, Panama and the Philippines, as part of the Phase II DEN-204 study, had a reduction in the incidence of dengue compared with placebo-treated children. Promising results were previously announced in March 2017 from a six-month interim analysis of the DEN-204 study. (Also see "Data Add To Strengthening Efficacy Case For Takeda Dengue Vaccine" - Scrip, 30 Mar, 2017.)
Developing a dengue vaccine that could be of use in younger children than Sanofi's marketed dengue vaccine, Dengvaxia, which is indicated for use in individuals aged around nine to 45 years, is one of the aims of Takeda's development of TAK-003; the still-ongoing Phase II DEN-204 study is assessing TAK-003 in children and adolescents aged from two to 17 years, in several different dosing schedules.
But the market is not been commercially lucrative so far – Sanofi recorded Dengvaxia sales of only €22m in the first nine-months of 2017. The company noted there have been challenges starting large public vaccination programs for a condition that has a relatively low disease incidence. (Also see "Sanofi's Dengue Vaccine Is World's First Approved" - Scrip, 10 Dec, 2015.)
Analysts at Datamonitor Healthcare suggest that public health campaigns could eventually start in markets such as Indonesia and Mexico, adding to sales in the private sector, although they noted that Dengvaxia's three-dose six-months-apart schedule is inconvenient. In clinical studies, Dengvaxia-vaccinated children aged below nine years had an increased risk of hospitalization, the cause of which was unknown but could be linked to weaker efficacy of the vaccine in younger children, and there was also weaker vaccine efficacy in seronegative subjects that had not been exposed to the virus.
As well as dengue, Takeda's recently formed specialized global vaccines business unit is also developing a norovirus vaccine, TAK-214, which is in Phase IIb studies, and has in Phase I an inactivated polio vaccine, TAK-195, being developed in partnership with the Gates Foundation. A human foot and mouth disease EV71 vaccine, TAK-021, is in Phase I, and the unit is considering a vaccine against Zika. Takeda has marketed a range of vaccines in Japan for 70 years (see sidebar).
TAK-003 Phase II Interim Results
In 1,794 subjects aged two to 17 years in DEN-204 who were given either one or two doses of the live attenuated, tetravalent vaccine, or placebo, an 18-month interim analysis showed those who received TAK-003 (also called TDV) had a relative risk of developing symptomatic dengue of 0.29 (95% CI: 0.13-0.72) compared with placebo-treated subjects.
TAK-003 contains a serotype-2 virus that has antigens found in all four viral serotypes, and its use was associated with sustained antibody responses against all four of those serotypes, regardless of previous dengue exposure and dosing schedule, the company said. The results of the DEN-204 18-month interim analysis were presented at the annual meeting of the American Society of Tropical Medicine and Hygiene on Nov. 7, and published simultaneously in The Lancet Infectious Diseases.
Dosing schedules evaluated included one primary dose, two doses three months apart, or two doses one year apart, or placebo, and across all doses TAK-003 was well tolerated, the company says. Antibody levels persisted for 18 months regardless of the dosing schedule. In patients who were seronegative at the start of the study, a second dose given after three months was associated with an 86% seropositivity after six month, compared with 69% seropositivity in subjects treated with one dose. Booster doses at 12 months increased seropositivity to 100% in subjects that were seronegative at the start of the trial, the company added.
The results support the use of a two-dose regimen given three months apart in the Phase III TIDES study underway in eight dengue-endemic countries, with data expected in late 2018.
The dengue virus is spread by mosquitoes and Takeda estimates the virus causes 390 million infections and leads to 20,000 deaths annually around the world.