Table 3 Products under development for severe malaria, or as artemisinin monotherapy
From: The global pipeline of new medicines for the control and elimination of malaria
Active ingredients | Partners | Phase/status | Â | Comments | References |
|---|---|---|---|---|---|
Intra-rectal artesunate | UNICEF-UNDP-World Bank-WHO Special Programme for research and training in Tropical Diseases (WHO-TDR) | Pre-registration | Â | Intra-rectal artesunate improves outcomes in sub-group in retrospective analyses: patients >6 hours from hospital, and <6 years old. No manufacturing or distribution partner has been defined. | |
Sevuparin sodium (DF-02) | Dilafor AB | Phase IIa | Â | Heparin analogue with a low anticoagulant activity. Phase I data were reported in Oct 2009 with doses as high as 420 mg. A Phase II study started in 2011 | [68] |
Artesunate for injection | Guilin Pharmaceutical | WHO prequalified 2010 | Â | Artesunate for injection has been produced since 1987. In 2010, Guilin gained WHO prequalification (with support from MMV). The clinical data in both the Aquamat and Seaquamat studies used Guilin material. Current price is $1.40 per 60 mg vial, over 2 500 000 vials sold in 2011 | [69] |
ARH1 (150 mg/ml artemether) | Lincoln Pharmaceuticals | Launched (India) 2011 | Â | ARH1, an injectable formulation of arteether (ethyl ether derivative of artemisinin). It is oil soluble, has a long elimination half-life (greater than 20 hours), and is more stable than other artemisinin compounds: launched in India in Jun 2011. | [70] |
SAR97276 (albitiazolium bromide) | Sanofi/CNRS | Phase II | Â | Bisthiazolium choline uptake inhibitor, not orally bio-available. Being developed as an intramuscular injection for severe malaria. Initial Phase II data showed relatively poor efficacy in uncomplicated malaria, and may require a higher dose. Medicine could have the advantage of being shipped in pre-filled syringes, making delivery simpler. | [71] NCT00739206 |
Artemether | Eastland Medical, Star Medical, Protopharma Ltd | Phase III | ArTiMist™ (sublingual mouth spray) | An artemether sublingual mouth spray. A Phase II study was conducted to compare the efficacy of ArTiMist™ and intravenous quinine in children infected with severe malaria, or uncomplicated malaria and gastro-intestinal complications (NCT01047436). The difficulty is to make sure this product does not break WHO’s call for the withdrawal of artemisinin monotherapy in uncomplicated malaria. | NCT01047436 NCT01258049 |
E6446 (TLR9 antagonist) | Eisai Co Ltd | Preclinical | Â | Toll-like receptor antagonists. TLR 9 antagonism has been suggested to suppress cerebral vascular lesions and leakage of vascular contents. The difficulties in interpreting the murine data mean additional proof of mechanism in humans will be needed before starting a severe malaria trial. |