Dr. Cristina Donini, Senior Director, Translational Medicine, MMV

MMV048 is a novel antimalarial compound from the aminopyridine class, with important activity across the entire parasite lifecycle. The compound was researched by an international team led by Prof. Kelly Chibale from the University of Cape Town, South Africa and was the first new antimalarial medicine to enter phase I studies in Africa.

Dr Cristina Donini explains her vision for MMV048, as well as the importance of getting the formulation right and building clinical trial capacity in Ethiopia.

1. What is your vision for MMV048?

MMV048 has the potential to become part of a singledose cure for uncomplicated malaria. One single dose would simplify malaria treatment and therefore increase compliance. The compound also has a novel mechanism of action that could help fight emerging drug resistance. If all this potential is confirmed, MMV048 could become part of a major tool for malaria elimination and eradication efforts.

2. Over the last year the team has been able to develop a new formulation with improved exposure. How did you achieve this?

Great teamwork between MMV, our expert consultants and a contract research organization made this possible. Based on our analysis of the exposure of the compound in the first-in-human study and the intrinsic characteristics of the molecule, we tweaked the composition of the existing formulation. From the in vitro assessment of several formulations, two were selected and tested in a bioavailability study in healthy volunteers and the one which provided the most consistent and increased exposure overall was chosen for further development. This is the formulation we will test in patients.

3. Why was the formulation development so critical to the project?

The previous formulation provided too much variability in exposure, which would lead to inconsistent dosing in patients and therefore not be consistently effective; this could pose a safety issue. It was critical to find a new formulation with less variability to be able to pursue the project.

4. What are the next steps?

The next step is the phase IIa clinical trial in patients as a single dose. The trial will begin in July 2017 in Ethiopia in adults with mono-infection of either P. falciparum or P. vivax malaria. To conduct this trial, we are working with Prof. Harald Noedl, of the University of Vienna, to strengthen the research capacity at two health facilities on the outskirts of Gondar and Jimma in Ethiopia. We are in the midst of building two dedicated patient wards and purchasing new equipment and lab supplies as well as training local staff in good clinical practice.

In parallel, we are looking at MMV048’s potential ability to protect against malaria infection. This will be tested in the Controlled Human Malaria Infection (CHMI) model, which is similar to the models that are used to test vaccines.

5. What’s exciting about this project for you?

This is a multifaceted project. We are not only developing a new medicine for malaria but also strengthening local research capacity and fostering lasting collaborations between European and African institutions. In the future, this capacity could be used for clinical trials for malaria as well as other diseases of poverty.