Developing child-friendly TB medicines for kids
In December 2012, the UNITAID Executive Board committed up to US$ 16.7 million to the Global Alliance for TB Drug development (TB Alliance) to support the development and production of appropriate paediatric TB medicine formulations.
Since 2007, UNITAID had been addressing paediatric TB through a market intervention with the Global Drug Facility of the Stop TB partnership. UNITAID investments enabled price reductions of up to 30% for key child TB formulations. However, in 2010, the WHO changed its guidelines for treating children with TB, recommending higher dosages. Since the dosages had changed as per revised WHO recommendations, more PK and formulation studies were needed for regulatory approvals. Manufacturers were reluctant to enter the market. As a result there were no quality assured medicines for the 500,000 new cases of paediatric TB annually. Infants and young children are at increased risk of suffering from severe forms of TB that can leave them incapacitated, deaf, paralysed or mentally disabled. TB spreads in close quarters, affecting whole families.
Many children are never diagnosed and the WHO was only able to provide the first official estimate of paediatric TB deaths in 2012: 64,000 in 2011. Public health experts agree that the actual number of child deaths is likely to be significantly higher. Nevertheless, the small number of cases means there is no market incentive for manufacturers to make adapted formulations.
The STEP TB Project proposes to provide improved access to correctly dosed, properly formulated, affordable, high quality TB medicines for children. Accordingly, it is planned that appropriately dosed, child-friendly formulations for HRZ, HR and E would be brought to market by the end of 2015, by at least 3 manufacturers (Many more manufactures were not deemed necessary as Paediatric TB market is a very small market and having too many manufacturers would fragment this small market and lead to loss of market synergies).
Project Outputs and Activities
The Project outputs are focused on activities that: 1) undertake market studies to understand the size and scope of the paediatric TB market, 2) undertake clinical studies, 3) do regulatory needs assessment related to paediatric TB drugs, 4) engage manufacturers and negotiate with them to bring the required drugs to market, 5) engage with countries to promote in-country uptake of recommended formulations, 6) engage with donors to ensure sustainability of the supply, and 7) disseminate lessons learnt.
In the first year of implementation TB Alliance and partners conducted a Global Consultation on Childhood TB estimation. Work on modelling to estimate potential market size was developed. Some of the market size estimation studies undertaken so far are as follows: Literature review of Paediatric TB treatment, Review of Paediatric drug formulation acceptability, Qualitative survey of non-NTP facilities, Rapid assessment of policy and practice, review of sales from existing manufacturers, procurement and consumption study in high TB burden countries, etc. TB Alliance also entered into negotiations with manufacturing partners. Four agreements with manufacturers have been finalised either to bring drugs to market or to develop a paediatric investigation plan (in the case of new drugs).
Currently consultations with regulators have started. Country engagement for Paediatric Plan development has made progress in a number of WHO regions with regional meetings being held. TB Alliance is also entering into an agreement with a new implementer for enhanced country engagement. A Paediatric Portal was launched on TB Alliance’s webpages at the link: www.tballiance.org/children