The combination of artefenomel (formerly known as OZ439) and ferroquine (FQ) has the potential to become the first of a new generation of antimalarials not based on artemisinin and therefore an important tool in the context of drug resistance. MMV and Sanofi are currently conducting a phase IIb programme to determine the safety and efficacy of the combination as a single-dose cure.
Dr Charles Wells, Head of Development/Associate Vice President, Infectious Diseases Therapeutic Area, Sanofi, USA, talks about the potential of artefenomel/FQ as a next-generation drug combination.
1. What is exciting about the artefenomel/FQ combination?
Artefenomel/FQ represents a novel class of drug with no apparent cross-resistance to existing treatments, meaning it has the potential to treat patients affected by drug-resistant parasites. It also has the potential to reduce dosing frequency, thereby improving adherence to treatment and preventing the emergence of further drug-resistant strains of parasite.
2. What are the challenges of developing an effective single/multiple-exposure radical cure?
Formulation is the key challenge to achieving a simplified therapy, either as a single or multiple dose, as it must be adapted for a range of patients, including those who are very young or very ill. Among others, a formulation that includes powdered milk to simulate food is under investigation. MMV has also worked with Sanofi and other manufacturing experts to resolve challenges in manufacturing quality and move the project forward.
3. What does the phase IIb programme involve? When will the results be available?
The programme includes two mirrored dose-finding studies: the first combines varying doses of FQ with a fixed dose of artefenomel; the second combines varying doses of artefenomel with a fixed dose of FQ. Results are expected in 2019.
4. Can you explain how this reduced-dose cure will work?
The treatment combines a potent, fast-acting agent (artefenomel) that can kill most parasites in the blood and quickly decrease the symptoms of malaria, with a long-lasting agent that clears the remaining parasites (FQ).
5. For a pharmaceutical company such as Sanofi, what are the advantages of partnering with MMV on this project?
MMV is a great organization with a lot of know-how in the field of malaria and antimalarial drug development. It is smaller and leaner than Sanofi, allowing for more flexibility. Partnership is vital to share the risks of development for tropical or neglected diseases; our partnership is a good model, and I highly value our collaboration on a personal and organizational level.