MORU has been working over the last 10 years on the development of triple artemisinin-based combination therapies (TACTs), combining two partner drugs instead of the conventional single partner drug in ACTs. This new combination therapy is needed to tackle the increasing problem of artemisinin and ACT partner drug resistance, which jeopardizes effective treatment of Plasmodium falciparum malaria. Artemisinin resistance started in the Greater Mekong Subregion (GMS) around 20 years ago, but has more recently emerged in several Sub-Saharan African countries.
Participants shared findings across all DeTACT project work packages, including drug development, clinical trials in Asia and Africa, mathematical modeling, bioethics, market positioning, communication and engagement, and individual patient data meta-analysis (IPD-MA).
The two TACTs developed under the project – artemether-lumefantrine plus amodiaquine (AL+AQ) and artesunate-mefloquine plus piperaquine (ASMQ+PPQ) – were evaluated in a randomized, placebo-controlled, partially-blinded clinical trial involving nearly 2,700 patients with uncomplicated P. falciparum malaria. Both combinations demonstrated excellent efficacy and safety, comparable to current ACTs. Notably, AL+AQ was more efficacious than AL in Cambodia, where nearly all infections were artemisinin resistant.
Mathematical modeling underscored the urgent need to deploy TACTs as soon as possible to delay antimalarial drug resistance, reduce treatment failures, and increase the likelihood of malaria elimination across diverse epidemiological settings. Complementary bioethical and market positioning studies identified potential implementation challenges and proposed practical solutions. Engagement efforts with national malaria control programs in 20 African countries and other stakeholders have significantly raised awareness about TACTs and their potential role. The reports from the IPD-MA will be submitted as part of the regulatory dossier for ALAQ registration and will be used to support TACT implementation and policy development.
The meeting also featured presentations on the DeTACT follow-up initiative: the ALAQ Fixed-Dose Triple ACT (FD-TACT) project – a collaboration between Fosun Pharma, MMV, Marubeni, and MORU – funded by the Global Health Innovative Technology (GHIT) Fund. This pivotal clinical trial to be conducted across five countries in Africa and Asia will confirm the efficacy, safety, and tolerability of a new fixed-dose combination of ALAQ developed by Fosun Pharma. Regulatory submissions incorporating outputs from the IPD-MA, national registrations, commercialization, ALAQ deployment roadmaps, and post-marketing pharmacovigilance will follow.
With successful trial outcomes and regulatory approval, ALAQ FDC will soon become a valuable new tool in the global fight against malaria.
- Text by Arjen Dondorp, Mehul Dhorda and Chanaki Amaratunga.
Photo courtesy of DeTACT.