Developing new products for vulnerable populations

Children

MMV has long recognized that developing better medicines for children helps address the most vulnerable patient population at greatest risk of dying from malaria. MMV and partners are developing and improving access to child-friendly formulations of existing antimalarials for treatment (artemisinin-based combination therapies; ACTs), and chemoprevention (sulfadoxine-pyrimethamine + amodiaquine; SP+AQ), as well as developing next-generation medicines for children in parallel with adult formulations.

The first product successfully co-developed by MMV and partners was Coartem® Dispersible (artemether-lumefantrine) , launched by Novartis in 2009. To date, 300 million treatments of this cherry-flavoured dispersible product have been distributed, making it the most widely distribute quality ACT for children. Later in 2015, Pyramax® granules (pyronaridine-artesunate), developed by Shin Poong Pharmaceutical and MMV, received a positive scientific opinion under Article 58 from the European Medicines Agency (EMA), becoming the second ACT specifically designed for paediatric use to receive approval from a stringent regulatory authority. A third ACT co-developed by MMV (with Sigma-Tau), Eurartesim® (dihydroartemisinin-piperaquine), was approved by the EMA in 2011 and received WHO prequalification in 2015. The paediatric formulation has completed clinical development and will be submitted for EMA approval.

Moving forward, MMV is developing next-generation medicines with paediatric formulations in parallel with adult formulations, thereby accelerating access to the main target population: children under the age of 5.

Pregnant women

Every year, 125 million pregnancies around the world are at risk from malaria.1 In Africa alone, approximately 10,000 women and 200,000 babies die annually as a consequence.2 Pregnant women have an increased risk of life-threatening outcomes, including cerebral malaria or severe anaemia.3 To diminish the risk of malaria during pregnancy, the World Health Organization (WHO) recommends a specific chemoprevention strategy, however, its acceptance and use is quite low.

Developing new drugs for use in pregnant women is extremely challenging. Pregnant women are excluded from trials of new drugs until the risks and benefits are well understood among non-pregnant adults, yet drug dosing can differ between these groups. Current WHO guidelines allow for the use of artemisinin-based combination therapies (ACTs) for women with malaria in the second and third trimester of pregnancy, but not for the first trimester when the foetus is most vulnerable, as there is an absence of key safety data. Additionally, in the absence of suitable alternatives some malaria experts suggest that ACTs could also be used as chemoprevention in pregnancy, which could lead to the problematic situation of the same medicines being recommended for both chemoprevention and treatment.

New antimalarial medicines that are well-tolerated in pregnancy are needed for both treatment and chemoprotection. While we cannot definitively predict which medicines will be suitable in pregnancy, we can identify early on which medicines would not be. Traditionally, preclinical studies to determine if a molecule has a safety signal are conducted in parallel with phase II studies. MMV has developed a strategy to move this testing forward so it is in parallel with the first-in-human studies in phase I.

This was successfully carried out for MMV048 and DSM265. We now propose taking this one stage further and systematically making safety in pregnancy one of the first safety tests performed in preclinical evaluation. In this way, we will ensure that medicines to protect vulnerable populations are identified as early as possible and prioritized for further development.


1 Manyando C et al. “A systematic review of the safety and efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria during pregnancy.” Malaria J. 11:141 (2012).

2 Dellicour S et al. “Quantifying the number of pregnancies at risk of malaria in 2007: a demographic study.”PLoS Med. 7(1):e1000221 (2010).

3 Schantz-Dunn J & Nour NM. “Malaria and pregnancy: a global health perspective”. Rev Obstet Gynecol. 2(3): 186–192 (2009).