Sanofi’s Dengue vaccine Dengvaxia has already proven controversial. But problems in the Philippines, where the vaccine was marketed until recently, did not stop an FDA advisory committee from yesterday recommending the product’s approval in the US.
However, the vote was mixed, and could stop Dengvaxia getting the nod across a broad age range, instead limiting its use to patients aged 9-17. Approval in this much smaller patient population would be good news for Takeda, whose rival dengue vaccine, TAK-003, recently succeeded in its pivotal trial, Tides.
Takeda has so far only said that Tides, a 20,000-subject study, met its primary efficacy endpoint, preventing dengue fever caused by any of the four serotypes of the virus, with “no significant safety concerns” so far.
The Japanese group has promised more data later this year. Industry watchers will be particularly keen to see TAK-003’s performance in children who have not previously been infected with dengue fever.
This is because there have been questions about Dengvaxia’s safety in this population after issues seen in the Philippines, where the vaccine was approved broadly and where a mass immunisation programme took place.
In late 2017 Sanofi was forced to limit Dengvaxia’s use to patients who had previously been infected, and admitted a link between the vaccine and more severe disease in previously uninfected patients who went on to contract dengue (Snippet roundup: Sanofi slips in dengue and Teva cuts top jobs, December 1, 2017).
It is thought that in dengue-naive people the vaccine could spur an immune response, predisposing them to a more severe illness upon a subsequent encounter with dengue.
Yesterday’s vote could make Dengvaxia’s US label narrower even than this. Sanofi had hoped to get the nod in people aged 9-45, but this looks in doubt after panellists split 7-7 on Dengvaxia’s safety, and voted 7-6 against its efficacy, with one abstention, in this age group.
The company had not studied Dengvaxia in this population: the two pivotal trials, CYD14 in Asia and CYD15 in Latin America, only enrolled children and adolescents. Thus Dengvaxia’s chances look better in a younger age group. In patients aged 9-17 the panelists came down 13-1 in favour of efficacy and 10-4 in favour of safety. The US FDA is due to make a decision by May 1.
Even if Dengvaxia gets the FDA's blessing it will not become the blockbuster that Sanofi once hoped.
And in the Philippines things look bleak. The country’s FDA revoked Dengvaxia’s approval in February, saying Sanofi had not fulfilled post-approval commitments. And this month the Philippine government announced plans to file criminal charges against 20 people, including six Sanofi employees, relating to the deaths of 10 children.
There are no treatments for dengue, which could help Dengvaxia’s cause with the US FDA. In Europe Dengvaxia is already approved for people aged 9-45 with a prior dengue infection.
But Sanofi could soon be facing competition from Takeda. If the Japanese group can show that TAK-003 is safe and suitable for broad use Dengvaxia's days might be numbered.