J&J joins amazing race

LONDON—Johnson & Johnson (J&J) has entered the raceto become the first company to discover, develop and market an effectivevaccine to treat Dengue fever—the world's fastest-spreading tropical disease,infecting up to 100 million people worldwide this year. Teaming up with academic researchers atthe University of Leuven (KU Leaven) in Belgium and the London-based WellcomeTrust medical charity, J&J believes it has the inside track to a cure—despitecompetition from Paris-based Sanofi Pasteur and Japan-based Takeda.

Spread by the Aedes aegypti mosquito, dengue has grown rapidly along with urbanization andglobalization because it thrives in tropical megacities and is easily spread ingoods containing small puddles of water. The World Health Organization (WHO)estimates that 50 million to 100 million infections occur each year. Theincidence has increased sharply in the last 40 years, and the disease nowaffects more than 100 countries. In 2009, the Florida Keys had its first casesin decades. Last year, Europe experienced its first sustained transmission ofdengue fever since the 1920s with around 2,000 people infected in thePortuguese archipelago of Madeira.

Ratcheting up the statistics, experts estimated in Aprilthat there may be as many as 390 million dengue infections around the worldeach year, although not all patients get seriously sick. Current approaches totreating the condition are focused on alleviating symptoms, rather thanattacking the cause. There is currently no drug treatment or vaccine for themosquito-borne viral disease that is also known as "breakbone fever" because ofthe severe pain it can cause the joints and muscles. Severe cases can involvebleeding and shock and can be fatal, particularly for children.

The collaboration of J&J's Janssen unit, researchers atthe KU Leuven and financial backing from Wellcome Trust will build on thediscovery of a series of chemical compounds that are highly potent inpreventing the replication of dengue virus. The compounds, which have yet to betested in clinical trials, are active against all four types of the virus andhave been shown to work in animal tests. Under the terms of the agreement,J&J made an undisclosed upfront payment and will make future milestonepayments to KU Leuven based upon the achievement of development, regulatory andsales goals.

Daniel De Schryver, global communications leader ofinfectious diseases and vaccines for Janssen J&J, says the collaborativeproject will build on an existing three-year drug discovery program at the RegaInstitute and the Centre for Drug Design and Discovery at KU Leuven, supportedby a Wellcome Trust Seeding Drug Discovery Award.

"There are several published mouse models for dengue virusinfection which allow evaluation of antiviral test compounds," De Schryvertells DDNews. "The chemical seriesinvolved in this collaboration have shown promising activity in such models."

J&J is realizing this race for a cure is more of amarathon than a sprint. Earlier this year, Sanofi suffered a setback when anexperimental shot from its latest dengue vaccine proved less effective in amid-stage clinical trial in Thailand. Still, the study marked a milestone inthe 70-year quest to develop such a vaccine, demonstrating that a safe andeffective inoculation against dengue is feasible. While previous trials weremeant to discover if a dengue vaccine was safe or could spur an immuneresponse, the Sanofi trial was the first to test whether a vaccine couldactually prevent the disease.

If Phase III clinical trial results fulfill Sanofi's hopes,the company will be poised to launch in 2015 and hit the ground running to meetthe massive global demand for dengue vaccine. It will also be comfortably aheadof competitors with pipeline candidates, such as GlaxoSmithKline, Merck &Co., Takeda/Inviragen—and now J&J.

Sanofi comes close in chase for vaccine

Sanofi's clinical trial results for a dengue fever vaccineare "the first ever demonstration that dengue vaccine is possible, and that'shuge," says Dr. Nadia G. Tornieporth, head of global clinical research anddevelopment at Sanofi Pasteur, and co-author of a study the company publishedin The Lancet. But in a commentarypublished in The Lancet, Dr.Scott B. Halstead, a senior scientific adviser to the Dengue VaccineInitiative, called the results "a complete surprise" and disappointing due tothe "enormous expectation."

The trial, conducted by Sanofi and Thailand's MahidolUniversity, involved 4,000 school-aged children ages 4 to 11, in Thailand'sRatchaburi Province. Two-thirds of the children received three injections ofthe vaccine over the course of a year, while the other third received threeinjections either of a rabies vaccine or a placebo. Among children who got allthree doses of either the vaccine or the control, there were 45 cases in thevaccinated group, representing 1.8 percent of that group, and 32 cases, or 2.6percent, in the control group. The difference was not statisticallysignificant.

The main problem was that there are four types of denguevirus and the vaccine failed to protect against one of them, known as serotype2. Unfortunately, it turned out that serotype 2 was the prevalent type in thatregion at the time of the study, accounting for more than half of theinfections in the trial, researchers reported.

It is unclear why the vaccine did not protect againstserotype 2, especially since the vaccine did spur an immune response to thatserotype. The good news is, the trial showed that the vaccine was safe andcould help dispel a theoretical concern that a vaccine could actually make thedisease worse.

Sanofi is already testing the vaccine in large Phase IIItrials involving more than 30,000 people in 10 countries, with results expectedin 2014. The dengue vaccine, which is made of live, attenuated viruses, is oneof the most important products in Sanofi's pipeline, with some analystsexpecting sales to exceed $1 billion a year. Sanofi spent about $450 million in2009 to build a new factory near Lyon, France, to make the vaccine. The planthas a design capacity of 100 million doses of the vaccine, tetravalent CYD-TDV,annually, according to Antoine Quin, manager of the site in Neuville-sur-Saone,France. In the meantime, Phase III trials are now underway in Asia and LatinAmerica, with results expected next year.