Named one of the top ten threats in 2019 by the World Health Organization, dengue is critically important to global health security as it infects up to 400 million people, sickens up to 100 million and kills thousands each year.
There are currently no approved therapeutics available to treat dengue, and research & development (R&D) has proven challenging, in part because of the existence of multiple dengue serotypes, each of which can cause reinfection and co-circulate in the same regions.
The Janssen Pharmaceutical Companies of Johnson & Johnson announced today, in collaboration with the KU Leuven Rega Institute and the KU Leuven Centre for Drug Design and Discovery (CD3), the publication of new preclinical data in the journal Nature showing that an early-stage compound with a novel mechanism of action could potentially treat all serotypes of dengue fever and provide a period of protection against acquiring the dengue virus. Janssen is now moving its dengue program into clinical development.
Data from the early-stage study suggest that an antiviral compound prevents the interaction between two viral proteins (NS3 and NS4B) that play an important role in the replication process of a virus, thereby stopping the ability of the virus to reproduce. This represents an entirely novel mechanism of antiviral action. The compound showed efficacy against dengue infection in a prophylactic setting, and rapid and significant reduction in viral load at peak viremia in a therapeutic model.
The virus is poised to impact billions more people in the coming decades as the Aedes aegypti mosquito that carries the dengue virus spreads further from its native regions, driven by converging trends like climate change, urbanization and a growing population. An August 2021 report from the Intergovernmental Panel on Climate Change also warns that warming temperatures could potentially drive increases in the incidence of vector-borne diseases, including dengue. As the frequency of outbreaks continue to dramatically grow, as evidenced by recent surges in South Asian countries including Bangladesh and Sri Lanka, the discovery of new treatment and prevention methods for dengue is greatly needed.
“As the climate continues to change and more communities are at risk, it is imperative that we advance our science to meet the needs of today and those to come,” said Ruxandra Draghia-Akli, M.D., Ph.D., Global Head of Global Public Health R&D at Janssen Research & Development, LLC. “Our breakthrough work in dengue signals what is possible when collaborative science is applied at the discovery phase and channeled toward great unmet need in public health.”
The Janssen dengue compound discovery program started in 2007. In 2013, Janssen collaborated with Professor Johan Neyts and Suzanne Kaptein at the KU Leuven Rega Institute and Patrick Chaltin at Centre for Drug Design and Discovery (CD3), as well as their respective teams, to identify a compound series capable of inhibiting the virus in lab-grown cells and animals. This effort built upon four years of work on the novel antiviral inhibitor by KU Leuven Rega Institute, CD3, and the Wellcome Trust. The development of the compounds was accelerated through the expertise and collaboration of all partners. Janssen Pharmaceutica, N.V. licensed the compound series in 2015, and is continuing to advance the compound into clinical development.