Clinical drug development for children with asthma

Oral presentation

Children are subject to many of the same diseases as adults, and by necessity, are often treated with the same drugs. According to the American Academy of Pediatrics only a small fraction of all drugs marketed has been studied in pediatric patients. Safety and effectiveness information for the youngest pediatric age groups is particularly difficult to find in product labelling. Inadequate dosing information may expose pediatric patients to the risk of adverse reactions or ineffective treatment through underdosing. FDA’s pediatric exclusivity provision provides six months of exclusivity to be attached to any existing patent protection on a drug for which FDA has asked for pediatric studies and where the manufacturer has conducted such studies. FDA has requested several pediatric studies which cover a broad range of diseases, including asthma.

In the past years, a number of important advances were made in the treatment of asthma, particularly with regard to children. New guidelines stress anti-inflammatory treatment early after diagnosis for patients who have persistent symptoms. The risk of adverse events associated with conventional doses of inhaled corticosteroids (iCS) is low, but in children with asthma concern remains about the potential effects of these compounds on growth. Short-term growth in children can be measured with knemometry. This technique measures changes in lower leg length that can be detected over periods as short as days. However, non-linearity of lower leg growth and the complexity of statural growth confound attempts to derive a predicted height from short-term measurements of the lower leg. Knemometry is better at detecting growth suppression than growth promotion. Long-term growth in children is measured with stadiometry. Growth velocity can only be determined from measurements of height taken over a period of at least 1 year. There have been several studies investigating growth velocity reduction and the prevalence of adrenal suppression in children, while, to our knowledge, there has only been one report to answer the question whether long-term treatment with iCS could interfere with body composition in terms of body fat accumulation. It has also been reported that treatment with iCS reduced the acquisition of bone mineral content in prepubertal children. There is no evidence that iCS at conventional doses have an adverse effect on the final height of children. However, questions are being raised about the appropriateness of early and long-term use of iCS in young children. On the other hand, it is important to be aware of the growth-impairing effect of poorly controlled asthma. In any case, the effect of early intervention with iCS in childhood warrants further investigation. Anti-leukotriene medications, such as montelukast, or phosphodiesterase 4 inhibitors (Phase III studies are currently being conducted) may be helpful in the management of persistent asthma. The pharmacokinetics, efficacy and safety of montelukast has been studied in a pediatric population.

A pediatric program should be included in the clinical development plan of every new molecular entity designed for the treatment of asthma if the product is likely to be used in a substantial number of pediatric patients or would provide a meaningful therapeutic benefit to pediatric patients. In comparison to oral dosage forms, it is more difficult to determine the appropriate dose range of inhaled asthma drugs in children since the clinical efficacy after topical administration cannot be predicted from PK data. Moreover, large-scale studies may be needed to demonstrate a dose-response relationship for inhaled anti-inflammatory drugs (e.g. steroids). The failure to produce drugs in dosage forms that can be used by infants can deny them access to important medications. That is why appropriate dosage forms should be available for young children.

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