Developing paediatric medicines
Children under the age of 5 years are the main victims of malaria. Yet few antimalarial medicines have been developed with children’s needs in mind, with the exception of Coartem® Dispersible, developed by the MMV/ Novartis partnership. This is an issue, because children are not simply little adults; they absorb and metabolize medicines differently. Additionally, antimalarial medicines are bitter; a child already nauseous from malaria may vomit the medicine and not receive a complete curative dose. Children need palatable medicines adapted to their weight and age.
MMV aims to address this imbalance. Child-friendly formulations of the recently approved Pyramax and Eurartesim are under development and are expected to be submitted for regulatory approval in 2014 and 2015, respectively.
Dr Isabelle Borghini-Fuhrer talks about the progress made and challenges of developing paediatric medicines. (2013)
1. What progress has been made to develop a paediatric formulation of Pyramax?
The current Pyramax tablets are approved to treat patients that are at least 20 kg. To address the needs of smaller patients the MMV/Shin Poong partnership have also developed a special granule formulation, which can be dispersed in a small amount of liquid. This will be much more suitable for children. The clinical studies have been completed, and the dossier will be submitted to the European Medicines Agency towards the end of 2014.
2. What are the challenges in the development of child-friendly medicines?
Recruiting children into clinical trials has very special ethical considerations and rightly so, as they are fragile, particularly as they are still developing. As a result, obtaining informed consent for a child to be involved in a study is more delicate than for an adult. It is therefore, safer to first start a trial with adults and be reassured about the risk–benefit profile of the drug before moving into children. These factors mean the development process for paediatric medicines is more complex and lengthy. Palatability is also a big issue in developing antimalarials for children, since these medicines can be very bitter making it difficult to administer a full dose to the child. Dosage is key for antimalarials; we must ensure a child gets enough medicine to cure them and to prevent the development of drug resistance. This can make formulation development more complex.
3. What lessons can be applied to the development of nextgeneration paediatric medicines?
One of the key things we have learnt is to think about the paediatric formulation right from the outset and even consider developing an adapted paediatric formulation that could be used in adults. We have also learnt how to ensure the stability of medicines in very warm and humid conditions. We now know which formulations and packaging can resist the heat. In addition, our access team has conducted market research, determining the importance of palatability and minimizing the volume of added liquid needed to administer the medicine. It’s also really important to find trial sites with experienced paediatricians who are malaria experts. The children enrolled in the trial must be monitored every 6 to 8 hours, and remain hospitalized, so it’s key to have somewhere nearby for the mother or family members to stay. Thankfully, we now have a really good network. One of our investigators in Gabon for the Pyramax paediatric trial, said that the medicine worked so quickly it made follow-up difficult as the children were already outside playing football and not in their beds!
Dr Isabelle Borghini-Fuhrer Director, Product Development, MMV