In the wake of controversy over a Sanofi (SNY) dengue vaccine, Takeda (TAK) Pharmaceuticals is betting its own effort will meet a largely unmet medical need and, in the process, become a best-selling product. But preliminary results released on Wednesday suggest the company has more work to do to ensure its vaccine does not encounter the same problems that have hobbled its rival.

A key hurdle Takeda must clear is to demonstrate that its own vaccine is not hindered by an issue that has clouded Sanofi’s Dengvaxia vaccine, which can actually make future cases of the mosquito-borne virus more severe in people who were not previously infected. After this finding was disclosed two years ago, a widespread vaccination campaign run by the Philippine government was abruptly halted amid scandal. Sanofi has struggled ever since to make a success of the product.

For the moment, Takeda reported preliminary results that are decidedly mixed. When taking into account all four serotypes, or strains, of the dengue virus, the Takeda vaccine demonstrated an overall 80.2% effectiveness rate. The late-stage study, published in the New England Journal of Medicine, tested two doses in more than 19,000 children and adolescents in eight countries.

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Breaking down the results further, though, shows a more nuanced story. In one strain — known as DENV-2 — the effectiveness rate was an impressive 97.7%. But effectiveness in two other strains — DENV-1 and DENV-3 — was much lower, at 73.7% an 62.6%, respectively. There was not enough data to assess the extent to which the vaccine mitigated the fourth strain, known as DENV-4.

“We’re very encouraged by the results,” Derek Wallace, a Takeda vice president who heads the dengue vaccine project, told us. Despite the moderate effectiveness displayed in two of the strains, the data “still represents a massive step forward in the reduction of the burden of the disease. We see it encouragingly when you consider the burden of (the) dengue (virus) globally.”

“We’re looking very carefully at the safety of this vaccine candidate on the assumption it continues to have no important safety side effects. A vaccine which has partial efficacy against some serotypes would still have significant public health advantages,” he continued, noting more data will be released later this month at a scientific conference. Wallace added that efficacy against hospitalization was also high.

 

Scientific experts, however, offered cautious assessments.

Scott Halstead, a retired dengue expert formerly at the Uniformed Services University of the Health Sciences who had published research warning about the problems with Dengvaxia, noted the Takeda vaccine shows some evidence of protection among children who were not previously exposed to the virus. He recently served on a Takeda advisory board.

Yet he also maintained that final results need to be seen. “We’ll have to wait to find out where that protection is going — will it stabilize or get worse? It’s very much a preliminary report,” he told us. “This suggests victory, but Takeda recognizes this is something they’re going to have to stick with, think about, work on, watch and be careful. … Let’s make sure nobody runs around claiming an early Pyrrhic victory.”

Meanwhile, Dr. Anna Durbin, a vaccine researcher from Johns Hopkins who has been involved in testing an as-yet unlicensed dengue vaccine being developed at the National Institute of Allergy and Infectious Diseases, also maintained that longer-term safety data, especially in children who were not previously infected with the dengue virus, is needed. Still, she struck a slightly upbeat tone.

“The overall efficacy against the four different serotypes is higher than with Dengvaxia and may be more balanced,” she wrote us. “I am cautiously optimistic because of the better efficacy in (children who were not previously infected with Dengue) than was seen with Dengvaxia and the similar efficacy in the younger age groups. This suggests to me that if there is an unbalanced response, the problem will be smaller than was seen with Dengvaxia.”

 

The results will be closely watched, given the fiasco that ensued with the Sanofi vaccine in the Philippines.

As we have noted previously, the saga began in 2017, when the Philippine government launched an immunization campaign using Dengvaxia. Public health officials hoped the vaccine would help eradicate a deadly scourge. Dengue kills about 20,000 people a year and infects hundreds of millions. About 830,000 children in the Philippines were eventually inoculated.

Sanofi, meanwhile, invested more than $1.5 billion over 20 years in hopes of delivering a blockbuster product to bolster its bottom line. But plans went awry after Sanofi subsequently acknowledged Dengvaxia could actually make future dengue cases more severe in people who were not previously infected. The company changed product labeling to limit use to people who were exposed to dengue in the past.

But Sanofi encountered criticism for some of its decisions in testing Dengvaxia. Although the company ran two trials involving more than 31,000 people, it looked at only a small subset of about 10% of these participants to gauge how the vaccine affected those who never had dengue fever. Sanofi’s interpretation of the clinical trial data also caused second-guessing.

By early 2018, Philippine authorities began questioning the speed at which the immunization program was begun, especially following reports that some children died after being vaccinated. Sanofi later refunded $29 million for unused vaccines, but twice refused demands to refund the cost of vaccines that were purchased, prompting the government to pursue a lawsuit.

Since then, the government filed criminal charges against former public health officials and threatened to pursue criminal charges against Sanofi. The Philippines later halted the sale, distribution, and marketing of Dengvaxia and also revoked Sanofi’s license after concluding the company failed to follow directives issued by health officials. Dozens of deaths were investigated.

More recently, though, Sanofi won a modest victory when the Food and Drug Administration approved Dengvaxia, but only for individuals ages 9 to 16 living in parts of the U.S. where the dengue virus is endemic — in other words, where it circulates on an ongoing basis. Dengue is found only in Puerto Rico and a few other U.S. offshore territories and protectorates. Moreover, the vaccine can only be given to children and teens who have had one previous laboratory-confirmed case of dengue.

Helen Branswell contributed reporting.

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