Severe Malaria, Pascalian Therapeutics, and the US Food and Drug Administration (FDA)

To the Editor— Malaria still kills over 1000 children each day, mainly in sub-Saharan Africa. Artesunate is the treatment of choice for severe Plasmodium falciparum malaria as it substantially reduces mortality compared with quinine [1], the previously recommended antimalarial treatment. Since 2015, the World Health Organization (WHO) has recommended parenteral artesunate treatment doses of 3 mg/kg for patients weighing <20 kg (ie. over 90% of African children with severe malaria) [2]. This was based on evidence from population pharmacokinetic modelling of data from over 300 children and adults with severe malaria [3, 4]. The US Food and Drug Administration (US FDA) has recently challenged this recommendation [5]. Using a population pharmacokinetic model that we developed [4], the US FDA simulated a virtual pediatric population with severe malaria from US Centers for Disease Control and Prevention (CDC) growth charts,...