The global pipeline of new medicines for the control and elimination of malaria

Abstract

Over the past decade, there has been a transformation in the portfolio of medicines to combat malaria. New fixed-dose artemisinin combination therapy is available, with four different types having received approval from Stringent Regulatory Authorities or the World Health Organization (WHO). However, there is still scope for improvement. The Malaria Eradication Research agenda identified several gaps in the current portfolio. Simpler regimens, such as a single-dose cure are needed, compared with the current three-day treatment. In addition, new medicines that prevent transmission and also relapse are needed, but with better safety profiles than current medicines. There is also a big opportunity for new medicines to prevent reinfection and to provide chemoprotection. This study reviews the global portfolio of new medicines in development against malaria, as of the summer of 2012. Cell-based phenotypic screening, and 'fast followers' of clinically validated classes, mean that there are now many new classes of molecules starting in clinical development, especially for the blood stages of malaria. There remain significant gaps for medicines blocking transmission, preventing relapse, and long-duration molecules for chemoprotection. The nascent pipeline of new medicines is significantly stronger than five years ago. However, there are still risks ahead in clinical development and sustainable funding of clinical studies is vital if this early promise is going to be delivered.

Figure 1

Chemical structures of anti-malarials described in Table1.

Figure 2

Sales (USD) of fixed dose artemisinin combination therapy 2006 2010. These data are compiled from estimates supplied by the WHO-prequalified manufacturers and from data provided by AMFm and include only WHO-prequalified or Global Fund-approved generic versions of the medicines. Sales of DHA/piperaquine have been around two million per year, and naphthoquine artemisinin around one million per year. Mefloquine-artesunate numbers are significantly lower. These numbers compare well with the lower range of the estimates predicted by the Clinton Foundation [42]. The total number of malaria patients was estimated by WHO to have fallen to 225 million in 2009 [7].

Figure 3

The global portfolio of anti malarial medicines under development organized by development stage (as of March 2012). This includes all projects in formal regulatory preclinical safety and pharmacokinetic studies. Projects carried out in collaboration with MMV are shown in open boxes, whereas those with no active MMV involvement are shown with a dashed border. Data are from MMV internal reports [59], and Thomson Pharma. Compounds have been defined as ‘on hold’ when no significant progress along the development process has been made publicly available in the last 12 months. Natural products are defined as Herbal Medicinal Products undergoing testing in malaria patients in GCP quality studies, using standardized extracts. Updates of this figure are available on a quarterly basis [60]).

Figure 4

The global portfolio of anti malarial medicines organized by therapeutic type. Compounds have been defined as ‘on hold’ when no significant progress along the development process has been made publicly available in the last 12 months. This analysis is important to show the emergence of new classes of medicines. Updates of this figure are available on a quarterly basis [60]).