Artefenomel (OZ439) plus ferroquine

Dr Laurent Fraisse, Vice President, Infectious Diseases R&D, Sanofi

Artefenomel, a novel trioxolane, is a front-runner candidate for inclusion in a new antimalarial combination with ferroquine. The combination is being specifically formulated for children and to allow for once-daily dosing. However, achieving an equivalent efficacy and safety profile in fewer doses than current 3-day ACT regimens is a major challenge. In partnership with Sanofi, MMV is aiming to overcome that challenge. The combination is currently in a phase IIb trial, which is expected to be completed in the fourth quarter of 2018.

Dr Laurent Fraisse talks about the added value of the combination as well as the advantage of working with MMV.

1. What could artefenomel plus ferroquine offer to the current antimalarial arsenal?

First, it would be a new-generation antimalarial combination, potentially the first not directly based on artemisinin derivatives. Given what we currently know about each compound, we are optimistic the combination will be effective against current resistant strains of malaria, although we don’t yet have clinical data to confirm this. It could therefore provide an alternative to current treatments and stop the progression of malaria to severe disease.

Second, the phase IIb trial is being conducted entirely with the combination as a single dose. Based on the blinded interim results generated so far, we are very optimistic. I believe a single-dose cure could make a big difference both to the individual patient and to the population as a whole. For patients, we know they will receive a complete cure. For the population, a complete cure decreases the chance of drug resistance emerging. Without a doubt, this is an important project in Sanofi’s portfolio.

2. What is the biggest challenge in the development of the combination?

The main challenge is the formulation. How can we provide a sufficient quantity of drug for a complete cure in one single dose in children and adults? How do we combine the two drugs and ensure optimal absorption? These are some of the questions we are working to resolve to ensure continued development of this exciting combination.

3. What are the next steps?

The next step will be an interim analysis of the phase IIb trial data expected in mid-2018. This will help us determine the best dose ratio between artefenomel and ferroquine. So far, we have assessed several doses of ferroquine in combination with one dose of artefenomel in adults. For the moment, it looks like all the doses are effective, but of course it’s all very preliminary data so we have to wait and see. The trial has been designed to enable us to test the drug combination in the younger population once the safety is established in the older age groups.

4. What is the added value of working with MMV on this project?

Working with MMV makes this possible as we share both risk and cost, and leverage the strengths and expertise of each organization to its full potential. MMV and its scientific committee are respected experts in the field of malaria research. Internally at Sanofi, we have other strengths but less malaria expertise, so to receive feedback from the senior scientists on MMV’s scientific committee is really important and vital to the success of the project. It’s also good to partner with a smaller organization like MMV that has the ability to be nimble in addressing issues and challenges that arise. At times, there can be differences of opinion that require adaptability on both sides, but ultimately the project benefits from the diverse expertise and culture the two organizations bring. As a result, we probably progress faster and the likelihood of success is much greater.

Finally, as MMV has a global view of malaria drug development, working in partnership guarantees that what we develop together will have enormous value for the patient.