Pitolisant (2) – Wakix®

• Clinical trials
  • Study P11-06 was a double-blind, multicentre, randomised, placebo-controlled trial lasting 8 weeks, followed by a single-blind 1-week washout phase and an open-label treatment phase to investigate the efficacy and safety of pitolisant.

Children and adolescents (aged 6–17) with narcolepsy, with or without cataplexy

• Hint for a non-quantifiable additional benefit, as the scientific data do not permit quantification.
• In its overall assessment of the available results on patient-relevant endpoints, the G-BA therefore classifies the extent of the additional benefit of pitolisant for the treatment of children and adolescents (aged 6–17) with narcolepsy, with or without cataplexy, on the basis of the criteria set out in Section 5(8) in conjunction with Section 5(7), first sentence, points 1 to 4 of the AM-NutzenV are non-quantifiable, as the scientific evidence does not permit quantification.
• mortality
  • Fatalities were recorded in the study as part of the safety assessment. No fatalities occurred during the 9-week blinded phase of the study.
• Morbidity – cataplexy and excessive daytime sleepiness (EDS) assessed using the CGI-C
  • The CGI-C endpoint is used for the clinical assessment of cataplexy and EDS by the investigating medical staff using a 7-point scale. A higher score indicates a worsening of symptoms.
  • For the CGI-C EDS endpoint, there was a statistically significant advantage for pitolisant compared with placebo.
  • For the CGI-C cataplexy endpoint, no statistically significant difference was observed between the treatment arms in the study.
• Morbidity – depressive symptoms assessed using the CDI-2 SF
  • The Children’s Depression Inventory (CDI-2 SF) is a tool for assessing depressive symptoms in children and adolescents. The total score ranges from 0 to 24 points, with higher scores indicating a worsening of symptoms.
  • As only descriptive results are available for the CDI-2 SF analyses, no conclusions can be drawn regarding the extent of any additional benefit for this endpoint.
• Morbidity – Suicidal behaviour using the C-SSRS
  • The Columbia Suicide Severity Rating Scale (C-SSRS) is a standardised clinical interview for the systematic assessment and close monitoring of the occurrence, intensity and frequency of suicide-related thoughts and behaviours. In this study, the analysis was dichotomised (suicide risk: yes/no).
  • As only descriptive results are available for the C-SSRS assessments, no conclusions regarding the extent of any additional benefit can be drawn for this endpoint.
• Morbidity – narcolepsy symptoms assessed using the UNS (presented as supplementary data)
  • The Ullanlinna Narcolepsy Scale (UNS) is a patient-reported questionnaire designed to assess the intensity and frequency of narcolepsy symptoms.
  • Overall, the available evidence does not permit a reliable assessment of validity for either the UNS total score or the cataplexy and EDS subscales. Due to the limitations described, this endpoint is not used for the benefit assessment.
• Morbidity – daytime sleepiness using the PDSS
  • As the direct relevance to patients for the present therapeutic indication cannot therefore be conclusively assessed, and as important information on validity is also lacking, the results for the PDSS are not taken into account for the assessment of additional benefit.
• Morbidity – Weekly cataplexy rate using a sleep diary
  • Due to uncertainties regarding operationalisation (e.g. no distinction between partial and total cataplexy; uncertainties regarding assistance from carers/third-party assessment when completing the diary) and in the validation process, this endpoint is not taken into account in the benefit assessment.
• quality of life
  • No quality of life endpoints were assessed.
• Side effects
  • There was no statistically significant difference in the overall rate of serious adverse events. In neither treatment arm of the study did serious adverse events or discontinuations due to adverse events occur.
  • On closer examination of specific adverse events with an incidence of ≥ 10% within the SOC ‘Infections and parasitic diseases’, a statistically significant advantage for pitolisant over placebo was observed.
• Overall assessment
  • Results from the 9-week randomised, double-blind, placebo-controlled study P11-06 are available for the benefit assessment of pitolisant in the treatment of children and adolescents (aged 6–17 years) with narcolepsy, with or without cataplexy.
  • No deaths occurred in either treatment arm during the study. No conclusions can be drawn regarding the extent of the additional benefit in the mortality category.
  • In the morbidity category, pitolisant showed an advantage over placebo for the endpoint of excessive daytime sleepiness, as assessed using the CGI-C. However, no statistically significant differences were observed in the analyses of cataplexy symptoms (assessed using the CGI-C Cataplexy). With regard to the endpoints of depressive symptoms (assessed using the CDI-2 SF) and suicidal ideation (assessed using the C-SSRS), no conclusions can be drawn regarding the extent of any additional benefit, as only descriptive results are available.
  • No data are available on quality of life.
  • In the category of side effects, there was no statistically significant difference in the incidence of severe adverse events. No severe adverse events or discontinuations due to adverse events occurred in either treatment arm of the study. In detail, for specific adverse events within the SOC ‘infections and parasitic diseases’, there was a statistically significant advantage for pitolisant over placebo.
  • In summary, therefore, an advantage for pitolisant over placebo is evident only for the endpoint of excessive daytime sleepiness as measured by the CGI-C. However, this advantage is not reflected in any other morbidity or side effect endpoints. Furthermore, only descriptive results are available for some endpoints. No data on quality of life were collected.
  • Against this background – and taking into account the short study duration – it is not possible to quantify the extent of the additional benefit.

Courtesy translation only, please refer to the German original.