17 December 2018 - - US-based pharmaceutical company Merck (NYSE: MRK) and Brazilian non-profit immunobiologic products producer Instituto Butantan have inked a collaboration agreement to develop vaccines to protect against dengue virus disease, the mosquito-borne infection, the company said.

Instituto Butantan and Merck have licensed certain rights from National Institute of Allergy and Infectious Diseases (NIAID), part of the United States National Institutes of Health, for the development of live attenuated tetravalent vaccines. Instituto Butantan's dengue vaccine candidate, TV003, is currently being evaluated in a large Phase 3 study in Brazil.

Under the agreement, Merck and Instituto Butantan have agreed to collaborate to share clinical data and other learnings from their respective dengue vaccine development programmes, both derived from licensed materials from the NIAID.

Instituto Butantan will receive a USD 26m upfront payment from Merck and is eligible to receive up to USD 75m for the achievement of certain milestones related to the development and commercialisation of Merck's investigational vaccine as well as potential royalties on sales. Instituto Butantan will retain responsibility for the manufacturing and commercialization of their investigational vaccine, TV003, in Brazil.

The agreement builds upon a productive long-term collaboration between MSD Brazil and Instituto Butantan, initiated in 2012, for human papillomavirus and Hepatitis-A vaccine products.

Dengue fever is a mosquito-borne disease that occurs in tropical and subtropical areas of the world. Mild dengue fever is characterized by a high fever, rash, and muscle and joint pain.

A severe form of dengue fever, (dengue hemorrhagic fever) can cause severe bleeding, a sudden drop in blood pressure and death. The World Health Organization has estimated that up to 400 m dengue infections occur annually, resulting in 500,000 hospitalisations.

Scientists in the Laboratory of Infectious Diseases at the NIAID of the NIH engineered a candidate live attenuated tetravalent vaccine against the dengue virus. NIAID then supported the development of the candidate vaccine through a series of clinical trials.

Instituto Butantan is sponsoring a placebo-controlled, double blind, multi-center Phase 3 trial evaluating a single dose of LATV produced at the institute in Sao Paulo.

The Phase 3 trial aims to enroll almost 17,000 healthy people aged 2 to 59 years in 15 cities.

All participants will be monitored for five years through a combination of in-person visits to the health clinic and telephone or text communications from the investigators.

The goal of the trial is to determine the efficacy of the vaccine for preventing dengue, and importantly to provide additional information about its safety. The principal investigator is Dr. Esper Kallas, for the University of Sao Paolo.

Instituto Butantan is the main producer of immunobiological products and vaccines in Brazil. Instituto Butantan carries out scientific missions domestically and abroad through the Pan American Health Organization, the World Health Organization, UNICEF and the United Nations.

The Institute collaborates with other agencies of the São Paulo State Secretariat of Health and the Brazilian Ministry of Health for the improvement of overall health in Brazil.