Stepping up development of child-friendly TB drugs

Babs Verblackt, CNS Special Correspondent
The development of drugs for pediatric TB is still in its infancy. But important steps are being made towards formulations that are more child-friendly. Now is the time to go the extra mile, bringing medicines to the market that serve those traditionally neglected in TB research: children suffering from the infectious disease. Pediatric TB is one of the main causes of death in children worldwide.

Each year in the 22 high TB burden countries an estimated more than 650,000 children develop active TB disease and more than 80,000 die. This is partly due to the current lack of accurate, reliable diagnostics and medicines in proper doses and formulations for children. When undergoing TB treatment children must make do with adjusted doses of the existing drugs in a lengthy and complex therapy that is hard to undergo and adhere to even for adults.

While worldwide research is underway to make TB therapy shorter, simpler and safer in general, several studies focus on the unmet need for new therapies for children in particular. Both child-friendly formulations of existing drugs as those of new drugs are being researched. "There is an amazing amount of research ongoing," Anneke Hesseling, Director of Pediatric TB Research Programme at the Desmond Tutu TB Centre at Stellenbosch University said, giving an overview of pediatric TB drug pipeline at the 45th Union World Conference on Lung Health in Barcelona.

Children with TB can be diagnosed, treated and do well, she emphasized. Yet in many cases it currently comes literally at a loss. Research shows, for example, that almost 20% of children undergoing treatment for multi-drug resistant TB (MDR-TB) suffer irreversible deafness. "Using the existing drugs better dosed, we can really optimize treatment in children," Hesseling said. 

Childhood TB and the need for improved medicines is still surrounded by many misconceptions, Malgosia Grzemska of the Global TB Programme at the World Health Organization (WHO) explained during the conference. "Such as the assumption that childhood TB would disappear simply by containing TB in adults; or that childhood TB is a low public priority," she said. "There is still a long way to go in the recognition of pediatric TB among child health programmes as well. They often say it is not their problem, but one that should be handled by the TB programmes."

Cherise Scott, TB Alliance
Photo credit: Babs V/CNS
The WHO has published a road map for childhood TB, a toolkit to combat childhood TB and several other guidelines/publications too. Grzemska points out that there is a huge difference in reporting to the WHO among the high burden countries. "Without a proper burden estimation, the interest of drug manufacturers probably will not be too high," she said.

"We have no clear understanding of how many patients there are, where they are located and how they are currently treated," Cherise Scott, Director Pediatric Programmes at the Global Alliance for TB Drug Development (TB Alliance), explained. TB Alliance is gathering data, trying to catalyze the market while pushing for more commitment from drug manufacturers and other parties involved. "We need producers who develop the right  medicines. We need the actual drugs and ongoing research into new drugs."

Children should not be treated as adults
All parties should start thinking on children differently--such as pharmaceutical companies who 'mostly assume a child should be treated as an adult', Scott told Citizen News Service (CNS) in an interview. "They hardly bother researching how medicines work in children unless it is for a disease that mainly affects children. Even in packaging and design everything is made for adults, not tailored to kids."

There is usually a big gap between when a drug gets on the market and when a child-friendly doses becomes available, if that happens at all. This gap is partly due to the rules set by regulatory bodies, which require the testing of medicines in a staggered way from older children to the very youngest child by different age groups which can take long periods to complete, "While there is not always a real need for that," Scott argues. "We are talking to regulators to try changing this situation-- shortening the time to launch highly needed child-friendly medicines." 

The ongoing STEP-TB project (Speeding Treatments to End Pediatric TB) of TB Alliance and the WHO funded largely by UNITAID is expected to deliver new child-friendly fixed-dose combinations of first-line TB treatments by early 2016. Next to developing the medicines, the project focuses on facilitating the availability, uptake and use of the improved TB medicines. This happens in partnership with the WHO and manufacturers, governments, donors, and many  others to ensure that the drugs get produced and delivered to the children who need them.

Hurdles in registration
"Because of hurdles in the registration of drugs in different countries, new products are not necessarily directly introduced once they are available," Scott told Citizen News Service (CNS). " This process currently takes two to six years, we hope to bring it down to less than one year. We need to push countries for fast track mechanisms, making these drugs sooner available to those who need them urgently. This is a major challenge.”

Many issues in childhood TB are linked to political will, she acknowledged. "Decision makers will listen to those making noise. If there is no noise, they do not listen. A lot of countries do not know or do not recognize that they have a problem called childhood TB. In diagnosis, treatment and health programmes, children often remain forgotten. They are seen as little individuals not transmitting the disease, so are not to worry about."

Easy steps
"Many countries do not plan or take adequate measures to identify children with TB or ignore to do so, claiming it would be too expensive or too difficult a process, even though there are easy steps one can take-- such as simply asking the question: does a child have symptoms of TB?

This is usually done for malaria and pneumonia, but not for TB. If an adult gets TB, often nobody will ask if there is also a child in the house. Children are not even brought to the healthcare centres. And if they eventually do reach specialized TB clinics or hospitals, it is usually quite late in the disease."

Despite all the challenges in childhood TB, Scott is hopeful. "In the past five years huge groups including the WHO, Stop TB Partnership’s Child TB Subgroup, Sentinel Project and UNITAID managed  to really push the issue. Several efforts and steps have already been made, we need to keep up that good momentum. It has been said that children with TB are the neglected among the neglected. I hope soon we will not say that anymore."

Babs Verblackt, Citizen News Service - CNS
1 November 2014
(The author is reporting for Citizen News Service (CNS) from the 45th Union World Conference on Lung Health in Barcelona, Spain, with support from the Global Alliance for TB Drug Development (TB Alliance). Email: