KAF156 belongs to a novel class of antimalarial molecules, the imidazolopiperazines, and in phase IIa trials was able to rapidly clear both P. falciparum and P. vivax parasites. On this basis, in 2017, KAF156¹ will enter phase IIb combination studies with the antimalarial lumefantrine.

MMV and Novartis are working together to develop the combination. The partnership builds on an already solid and successful history of collaboration in antimalarial drug development, which in 2009 led to the launch of the first high-quality artemisinin combination therapy for children.

David Hughes talks of the promise that KAF156 holds as a future antimalarial, as well as the path ahead to help realize that promise.

1. What is exciting about KAF156 as a potential antimalarial?

KAF156 is potent across multiple stages of the parasite lifecycle, which means it has the potential not only to cure the clinical symptoms of malaria in a single dose but also to block its transmission, thus protecting people from actually contracting the disease in the first place. It also appears to be active against current resistant strains of the parasite. There are real concerns around the emergence of resistance in the field to both artemisinin and its partner drugs, which have been reported in Asia. Recently, we have begun to see the first potential signs of reduced sensitivity to artemisinin in Africa. The sooner we can have compounds that are effective against resistant parasites the better.

2. How could KAF156 in combination with lumefantrine contribute to malaria elimination?

To build on the gains that we've made over the last 10 years against malaria and ensure we don't slip back, we need easy-to-administer medicines, effective across all ages, types of resistance patterns and geographies. KAF156 plus lumefantrine has the potential to play an important part in continuing this progress and, in doing so, to help endemic countries move towards malaria elimination.

3. What are the plans for the phase IIb study?

The phase IIb study is due to start in July 2017. We will be testing KAF156 as a once-daily administration for 1, 2 and 3 days. In many respects, it’s set to be a groundbreaking trial, employing a number of adaptive trial design features. The study will characterize different combinations of KAF156 and lumefantrine, for different durations, in different patient groups (adults, adolescents and children). As the treatment of children represents the biggest unmet need, the goal is to begin including them in the clinical trial as quickly as possible. We've really tried to think through scenarios to accelerate the drug’s development while ensuring patient safety and we’re confident the design chosen will achieve this.

4. Why was lumefantrine chosen as the partner drug for the phase IIb study?

Lumefantrine is a tried and tested antimalarial. It has been used in combination with artemisinin in Coartem® for a number of years as a very effective standard-of-care, particularly in sub-Saharan Africa. In addition, we have been able to reformulate it to allow once-a-day dosing for multiple days.

5. For a large pharmaceutical company like Novartis, what is the advantage of working with MMV?

Novartis and MMV not only have a long-standing history of successful collaboration in malaria research, but we also have some very complementary skills and experiences. MMV’s international network of partners provides an efficient way for us to quickly access clinical experts, both from academia and MMV’s own staff, and we benefit from MMV’s advice to complement our own experience on operational aspects of how and where to conduct clinical trials. In addition, MMV provides effective access to other third-party funders who want to contribute to the global fight against malaria.

1. KAF156 is the result of a Wellcome Trust, MMV and Singapore Economic Development Board-supported joint research programme with the Genomics Institute of the Novartis Research Foundation, the Novartis Institute for Tropical Diseases, the Netherlands Primate Research Centre and the Swiss Tropical and Public Health Institute.