Table 1 Fixed - dose artemisinin combination therapy approved or in development (as of November 2011)

Artemether (20 mg), lumefantrine (120 mg) x 4 b.i.d

Novartis, MMV

Launched 2008

Coartem^®; Coartem^®-Dispersible

Coartem was launched in 2001. Coartem Dispersible is a specific paediatric formulation with a sweet-tasting flavour. It is given twice per day for three days. Coartem Dispersible decreases gametocytes by 6–8- fold compared to sulphadoxine/pyrimethamine and chloroquine. Approved by Swissmedic in Dec 2008, it received WHO prequalification in Feb 2009. Four dose strengths are registered in 83 countries. In Apr 2009, Novartis received approval from the US-FDA for Coartem, including a ‘Priority Review Voucher’ (PRV).

a), f)

[10–17]

Artesunate (100 mg), amodiaquine (270 mg) x 2 q.d.

Sanofi, DNDi (MMV)

Prequalified 2008

Coarsucam^®; ASAQ-Winthrop^®

Marketed as Coarsucam in the private market and ASAQ-Winthrop in the public markets. Given once per day for three days. Originally registered in Morocco, it is now approved in 31 countries (including 25 in Africa) and prequalified in 2008 by WHO, but so far has not been submitted to a Stringent Regulatory Authority. Stability data now available for three years in Zone IVb (30°C and 75% relative humidity), compared to two years for other ACT.

b), g)

[18–23]

Dihydroartemisinin (40 mg), piperaquine (320 mg) x 3 q.d.

sigma-tau, MMV, Chongqing Holley Holding

Approved

Eurartesim^®; Artekin^®; Duo-Cotecxin^®

Available as Duo-Cotexcin since 2005 (approved by Sino-FDA), uses the active metabolite of artemisinin, dihydroartemisinin. Given once per day for three days. Two pivotal clinical trials led to approval by the EMA in 2011. Prequalification expected 2012. Shows superiority to artemether-lumefantrine in post-treatment protection until day 63.

c), d)

[24–29]

Pyronaridine (180 mg), artesunate (60 mg)

Shin Poong, MMV

Pre-registration

Pyramax^®

Approved by the Korean K-FDA, and by the EMA, article 58 in Feb 2012. Prequalified by WHO. Given once per day for three days. Four pivotal clinical studies were performed 2007–2009, with the first regulatory studies on an ACT in both Plasmodium falciparum and Plasmodium vivax malaria. Shows superiority to artemether-lumefantrine in post-treatment protection until day 42.

g), b)

[30–33]

Mefloquine, (200 mg), artesunate (100 mg), x2 qd

Farmanguinhos, DNDi, (Cipla Ltd, MMV), Mepha Ltd

Launched (Brazil) 2008; Launched (Portugal) 2003

ASMQ; Artequin

A fixed-dose combination from Farmanguinhos (Brazil)/DNDi was registered in Brazil in 2008. Given once per day over three days. Use outside Brazil should be accelerated by production by Cipla (India), and Indian registration in 2012. Prequalified by WHO in September 2012. Fixed-dose combination called artequin granules (50 mg artesunate/125 mg mefloquine), originally registered in Portugal (2003) and now sold in Africa in commercial markets.

e), b)

[34–38]

Artemisinin (125 mg), naphthoquine (50 mg) x 8 tablets

Chinese Academy of Military Medical Sciences, Kunming Pharma Corp

Launched (China)

ARCO^®

Combination of poorly bio-available artemisinin with naphthoquine. Given either as a single dose or split twice within the same day. Clinical studies are not GCP compliant, and report on a limited number of patients. Very little preclinical data available for review. Registered and promoted in more than 10 countries.

a), h)

[39–41]