MMV048 is a novel antimalarial compound from the aminopyridine class, and the first new medicine to be discovered by an African-led team. In 2014, it entered phase I. This is the first time a new antimalarial has entered volunteer studies in Africa. MMV048 is highly potent against the blood-stage of malaria – active at doses of less than 100 mg, so at this stage it appears to be at least 10-fold more potent than many medicines used today. As such, it could be a really important part of a single-exposure cure. The compound also has activity against other stages of the parasite lifecycle and all known resistant strains of the parasite, suggesting a role in malaria control, transmission blocking and eradication.
The phase I safety study is being conducted at the University of Cape Town (UCT), South Africa, led by Dr Phumla Sinxadi and Prof. Karen Barnes in collaboration with the South African Technology Innovation Agency.
Dr Phumla Sinxadi, Clinical Pharmacologist at UCT and Lead Investigator for the MMV048 study, explains the goal of phase I studies and how MMV048 is progressing.
1. What is the goal of phase I studies and what do they involve?
The goal is to evaluate the safety and tolerability of the novel compound, in this case MMV048, in healthy volunteers. The first of these studies is known as the ‘first-in-human study’. We invite healthy volunteers to participate, by placing adverts in local newspapers – and others hear about the study from past participants. We then screen them to see if they are suitable to be part of the trial. We have screened more than 200 volunteers and dosed 40 subjects, eight of whom have returned for repeat dosing.
2. What factors contributed to the successful completion of the phase I study by UCT?
We have quite a supportive environment with guidance from the UCT human research ethics committee, Triclinium CRO and the South African Medicines Control Council. We also have an international panel of safety experts that look at all the results after each dose before we continue to the next. Its early days, but the good news is that there are no major safety concerns to date.
Prof. Karen Barnes, Clinical Pharmacologist at UCT and Principal Investigator of the phase I trial of MMV048, describes why the compound and development programme are unique.
1. What is unique about the development programme for MMV048?
We are at a very exciting phase with MMV048, as this is the first antimalarial compound researched in Africa to progress to phase I clinical trials. Although we have conducted a number of other phase I studies, this is the first time that our group has taken on a first-in-human study.1 Malaria is highly prevalent in Africa, so it’s important to study new drugs as early as possible in African populations. We are committed to this research. 2. What is MMV’s role in this programme? MMV plays a pivotal role. They bring with them 15 years of experience in developing better and new treatments for malaria. I don’t think either UCT or the South African Government would have felt as confident undertaking this kind of study without MMV’s technical support. MMV has also been a major co-funder with the South African Government’s Technology Innovation Agency
1. Phase I trials include a series of studies conducted in healthy volunteers to determine the safety of the molecule, the first of which is known as the ‘first-in-human study’.
Dr Phumla Sinxadi, Clinical Pharmacologist at UCT & Prof. Karen Barnes, Clinical Pharmacologist at UCT