Sanofi Has Setback With Dengue Vaccine

Sanofi Has Setback With Dengue Vaccine

September 12th, 2012 // 5:17 pm @ jmpickett

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Two months ago, Sanofi issued a press release indicating results of a widely awaited vaccine to prevent dengue fever, which is estimated to threaten some 3 billion people worldwide, demonstrated proof of efficacy. Late last night, though, study results were published in The Lancet showing something quite the opposite – the vaccine was only 30 percent effective in its first large clinical trial, a statistically insignificant outcome.

“This result knocked me off my chair,” Scott Halstead, a senior scientific adviser for the non-profit Dengue Vaccine Initiative, who was not involved in the study, told Reuters. “This is a very sobering outcome and a lot of thought and further experimentation is going to have to be done in order to understand what happened. You can’t be very confident that this vaccine is going to significantly reduce human illness.”

The findings were attributed to a failure to protect against one type of dengue virus, which turned out to be the prevalent strain in Thailand during the study. Until now, though, researchers had been anticipating the vaccine would offer protection exceeding 70 percent. Although the study demonstrated it is possible to generate a safe and effective vaccine, the outcome is a setback for Sanofi, which has been anticipating a billion-dollar product.

Just the same, the drug and vaccine maker put a positive spin on the disclosure. The results are “the first ever demonstration that dengue vaccine is possible, and that’s huge,” Nadia Tornieporth, an author of the paper and head of global clinical research and development at Sanofi Pasteur, the unit that is developing the vaccine and sponsored the trial, tells The New York Times.

As the paper writes, a vaccine is “considered crucial because there is no specific treatment for dengue, and no way to prevent the disease other than controlling the mosquitoes that transmit it. Infection by dengue virus can cause high fever and intense joint and muscle pain. Severe cases can involve bleeding and shock and can be fatal, particularly for children.”

The mosquito-borne disease is caused by four different types of virus, none of which provides immunity from the others. Sanofi issued a July 25 press release indicating its vaccine was effective against three of the four strains, but did not provide details, other than to say an analysis was under way to understand the lack of protection for the fourth serotype “in the particular epidemiological context of Thailand” (read here).

The Phase II trial involved 4,000 children between four and 11 years old. Two-thirds received three injections over one year, and the rest received three injections of a rabies vaccine or a placebo. Among those given all three doses of either the vaccine or the control, there were 45 dengue cases in the vaccinated group, or 1.8 percent, and 32 cases, or 2.6 percent, in the control group. This was not a statistically significant difference (here is the study).

Consequently, there are now several questions about why the vaccine failed to protect against one type of dengue fever, whether there are any geographic considerations pertinent to this finding and to what extent the use of the vaccine may now be delayed in favor of awaiting results of a later-stage trial.

“A completed clinical trial of vaccine efficacy should be cause for celebration for the billions of people who live in the 128 countries where dengue viruses are transmitted,” Halsted wrote in an accompanying commentary piece in The Lancet that was entitled “The 75 Percent Solution?” (read here). “However, the celebration will be muted this time…” He criticized Sanofi for not studying a larger number of patients in this particular trial and called this “a cautionary tale.”

Meanwhile, Sanofi was also criticized for its July press release, which did not disclose that the vaccine had not provided statistically significant protection overall. “This is certainly not the way I would have described this trial,” Halsted tells the Times. Today’s press release also downplayed the disappointment and, instead, emphasized the “excellent safety profile” and the fact that the vaccine succeeded in preventing three of four virus types.

While drugmakers are certainly free to play up positive results, a decision to omit significant information can undermine credibility with the medical community, patients and investors, as well. Sanofi may argue that the July release candidly noted that full results would be disclosed shortly, but chose to trumpet efficacy without painting a fuller picture. As vaccine efficacy goes, this is a sticking point.

[UPDATE: A Sanofi spokesman wrote us to acknowledge that, although the serotype 2 “diminished the overall vaccine efficacy caused by any serotype… “in the intent to treat analysis, disease incidence and the number of cases per serotype provide evidence of protection against 3 serotypes with various statistically significant efficacy levels per serotype (from 61 percent to 90 percent).” He also noted that the later-stage trial involves more than 31,000 patients in hopes that a larger population from different epidemiological environments will clarify matters.]