Merck and Brazil's Instituto Butantan Team to Develop at Least Two Dengue Vaccines
Dengue fever infects as many as 400 million people annually, according to the U.S. Centers for Disease Control and Prevention (CDC). It is the leading cause of illness and death in the tropics and subtropics. The virus is transmitted by mosquitos. The most common symptoms are high fever, severe headache, severe pain behind the eyes, joint pain, muscle and bone pain, rash, and mild bleeding from the nose or gums. At its worse, the disease can lead to failure of the circulatory system and shock, followed by death.
Merck and Instituto Butantan have licensed specific rights from the U.S. National Institutes of Health (NIH)’s National Institute of Allergy and Infectious Diseases (NIAID), related to the development of live attenuated tetravalent vaccines (LATV).
The Instituto Butantan also has a dengue vaccine candidate, TV003, which is in an ongoing Phase III clinical trial in Brazil. The trial expects to enroll almost 17,000 healthy individuals between the ages of 2 and 59 years in 15 cities. All patients in the trial will be monitored for five years by way of in-person visits to the health clinic and telephone or text communications.
Under the terms of the deal, the two partners will collaborate to share clinical data from their respective dengue vaccine development programs, which both came out of the NIAID. Merck will pay Instituto Butantan $26 million upfront. Instituto Butantan will be eligible for up to $75 million in development and commercialization milestones, in addition to possible royalties.
The Instituto Butantan will be responsible for manufacturing and commercialization of TV003 in Brazil.
“This agreement recognizes the tremendous progress that scientists and clinicians at the Instituto Butantan have made in developing their investigational dengue virus vaccine,” stated Roger M. Perlmutter, president, Merck Research Laboratories. “Through our new collaboration, we together have made a commitment to help protect people around the world who are at risk of developing dengue virus disease.”
The first dengue vaccine, Dengvaxia, was developed by Sanofi Pasteur, and was first registered in Mexico in December 2015. Dengvaxia is a live recombinant tetravalent dengue vaccine. The World Health Organization (WHO) indicates there are at least five other vaccine candidates being studied in clinical trials.
There is some controversy related to Dengvaxia, at least in the Philippines, where the vaccine has been banned for the last year. The vaccine is not recommended for people who have been previously infected by dengue virus, and Sanofi Pasteur indicated in December 2017 that it planned to update its label.
Dengvaxia is also being evaluated by the U.S. Food and Drug Administration (FDA). It has a target action date of May 1, 2019.
Dengue is caused by four closely related flaviviruses, Dengue viruses 1, 2, 3 and 4. Getting the disease from one does not necessarily provide immune protection from infection by one of the others. And, a secondary infection is generally linked to greater severity of disease.
WHO notes, “Due to these dengue-specific complexities, vaccine development focuses on the generation of a tetravalent vaccine aimed at providing long-term protection against all virus serotypes. Additional challenges are posed by the lack of an adequate animal disease model and the resulting uncertainty around correlates of protection. In spite of these challenges, vaccine development has made remarkable progress in recent years, and the current dengue vaccine pipeline is advanced, diverse and overall promising.”