While many medications are used in the pediatric population, they often have not been specifically tested in children. Absent pediatric data, regulatory agencies give the medications a labelled indication just for adults. In order to prescribe these prescription medications that are approved and labelled for adult use to children, physicians are able to use their best medical judgment and prescribe them off-label. Many prescription medications are prescribed to children in this way. Modafinil (Provogil), for example, does not have an indication in children. While the prescribing information for Modafinil details some of the studies that have been performed in children, it concludes that the relatively poor efficacy and high risk of side effects seen in the young patient population does not justify a pediatric indication. Lithium is another medication that is often prescribed to children even though the prescribing information (https://www.drugs.com/pro/lithium.html) specifies that, “Since information regarding the safety and effectiveness of Lithium in children under 12 years of age is not available, its use in such patients is not recommended at this time.” And while Zoloft is approved for the treatment of children with obsessive compulsive disorder (http://labeling.pfizer.com/ShowLabeling.aspx?id=517), it is not approved for pediatric major depressive disorder, panic disorder, or other indications. The package insert for Zoloft also contains a black box warning emphasizing the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults that is associated with the use of Zoloft. Despite that, Zoloft is frequently prescribed off-label to the pediatric population.
Medications are prescribed off-label to children because they meet an unmet need, and in the judgement of the child’s physician the benefits of the medication outweigh any risks. If both the physician and the parents are willing to assume these risks when presented with the alternative of no, or inferior, treatment, then the medication is provided to the child. Many physicians, however, await trials that demonstrate safety and efficacy in the pediatric patient. This is especially the case for physicians treating children diagnosed with rare diseases such as Prader-Willi Syndrome (PWS) and narcolepsy. But often these trials are only conducted following a period of off-label use in children when the data can actually be generated. This gap in pediatric clinical trials is recognized by the FDA and they have guidelines for extending the patent protection for products specifically tested in the pediatric population for approval in children.
Thankfully, Bioprojet has initiated a pediatric trial of pitolisant. The first results from the trial were presented at the 23rd Congress of the European Sleep Research Society. The researchers described the tolerance and pharmacokinetics of pitolisant in 24 children with narcolepsy. The investigators reported at the meeting that the 18 mg single dose was tolerable in the patients aged 6-18. The researchers found no differences in tolerability based upon age or gender. They did note, however, that body weight affected dosing exposure and therefore suggested that pediatric dosing take into consideration the weight of the child.
The pediatric trial is still ongoing and should be completed at the end of 2018 (https://clinicaltrials.gov/ct2/show/NCT02611687?term=pitolisant&rank=2). The study sites are located throughout the European Union in France (Bron and Paris), Finland (Helsinki), and Italy (Bologna). In order to be included in the study, patients must be between the ages of six and 18 years of age and be diagnosed with narcolepsy with or without cataplexy.
Bioprojet is also conducting many other trials on the use of pitolisant (https://clinicaltrials.gov/ct2/results?term=pitolisant&Search=Search). These include several trials to evaluate its efficacy in the treatment of excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA). The company has also completed trials evaluating the efficacy and safety of treatment with the combination of pitolisant and modafinil in patients with cataplexy and narcolepsy. Finally, the company has completed some trials and has proposed others to evaluate the effect of pitolisant in the treatment of patients with Parkinson ’s disease and patients with alcoholism.
We welcome the preliminary data on the safety and efficacy of pitolisant in the pediatric population and we look forward to learning more about its ability to benefit this vulnerable population.