We must not leave kids behind in our efforts to eliminate malaria.
Primaquine has two key roles in malaria elimination – blocking the transmission of Plasmodium falciparum and the radical cure of P. vivax and P. ovale. A single, low dose of primaquine is given with standard treatment for transmission blocking while radical cure primaquine is generally given over 14 days. All vivax- and ovale-infected patients need primaquine and, if the WHO recommends primaquine for transmission blocking outside of low transmission areas, then all falciparum patients will also need primaquine.
Primaquine is a cheap antimalarial drug that was developed in the 1940s in the United States where a 15 mg tablet was registered in 1952. Some 10 years ago, a 7.5 mg primaquine tablet was registered in the European Union, bringing the total number of quality-assured primaquine tablets to two. The availability of only two tablet strengths produced to international standards makes malaria elimination virtually impossible.
Added to this is primaquine’s bitter taste which leads to low acceptability and adherence in children who must receive treatment as a suspension of the crushed coated tablet. We need to meet this challenge so that children are adequately treated.
Developing and deploying quality-assured, child-friendly primaquine across a range of doses in optimised regimens for transmission blocking and radical cure would be a very substantial step forward in tackling the global malaria burden of some 229 million clinical cases (2019).
This is the goal of our Developing Paediatric Primaquine consortium.
Strategy
Global vision
Antimalarial drugs that are used in malaria control programmes are usually procured externally. Procurement is supported by the Global Fund, USAID and other international agencies but the purchased drugs should be quality-assured. This can be achieved by developing essential medicines through the World Health Organization (WHO) prequalification programme, which is essentially the same as registering a drug with a stringent regulator authority. Once prequalified, the drugs can be marketed via the WHO accelerated registration scheme of prequalified drugs.
To ensure the development of optimised treatment regimens that also enhance patient adherence, multiple tablet strengths and acceptable dosage forms are required. This challenge can be addressed by developing child-friendly formulations, optimising the packaging, and assessing their acceptability by patients and healthcare providers. This early research development work has to be conducted in partnership with a drug manufacturer that is both willing and has the capacity to ensure the scale up, manufacture and marketing and distribution of the quality-assured finished product in malaria endemic countries.
Overview of our strategy
DPP approach
Our approach has been to identify the major gaps in treating paediatric patients with malaria.
Firstly, there are no WHO recommended regimens for transmission blocking or radical cure that are allometrically scaled or state clearly the dose to give for a given weight band. The number of currently available, quality-assured primaquine tablets is inadequate – just two – 15 mg, produced by Sanofi, is registered in the US, and 7.5 mg, produced by Remedica, is registered in the European Union.
There are no paediatric primaquine tablets or user-friendly formulations that are approved by a stringent regulatory authority or prequalified by WHO. Pharma is reluctant to develop drugs for neglected diseases like malaria because profits are small. Therefore, other groups must fill this void and support pharma to contribute to overcoming key obstacles to global malaria elimination.
We have consulted the WHO on the necessary steps to achieve prequalification and developed a programme of work in accordance with the March 2019 WHO Expression of Interest. We then set about looking for funds, a task that proved challenging. Undeterred, we responded to the 2019 EDCTP (European and Developing Countries Clinical Trials Partnership) call for “Paediatric drug formulations for poverty-related diseases” and were fortunate to have been awarded a grant.
The Developing Paediatric Primaquine project is an African European consortium working in partnership with IPCA, our industrial partner, and several other specialist groups.
DPP’s principal aim is to increase access of quality-assured primaquine of all ages and accelerate malaria elimination worldwide by:
- answering the March 2019 WHO call for prequalifying an expanded range of tablet strengths of quality-assured primaquine: 2.5, 3.75, & scored 5, 7.5 & 15 mg
- going the extra mile by developing child-friendly palatable formulations through taste-masking studies and undertaking early granule development
- assessing the acceptability of flavoured primaquine tablets and prototype blister packs.
