Omaveloxolon (1) – Skyclarys®

• Clinical trials
  • Part 2 of the MOXIe trial is a multicentre, randomised, controlled, double-blind study phase designed to investigate the safety and efficacy of omaveloxolone compared with placebo.

Adults and adolescents aged 16 years and over with Friedreich’s ataxia

• 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 omaveloxolone for the treatment of Friedreich’s ataxia in adults and adolescents aged 16 and over, on the basis of the criteria in Section 5(8)(i)in conjunction with Section 5(7), first sentence, points 1 to 4 of the AM-NutzenV, as non-quantifiable, because the scientific evidence does not permit quantification.
• Overall, there is a hint of a non-quantifiable additional benefit of omaveloxolone for the treatment of Friedreich’s ataxia in adults and adolescents aged 16 and over, as the scientific evidence does not permit quantification.
• The MOXIe Part 2 study, on which the benefit assessment is based, exhibits a high potential for bias.
• On balance, the validity of the evidence is classified as a hint.
• mortality
  • Deaths were recorded as part of the safety monitoring. No deaths occurred.
• Morbidity – Physical functioning assessed using the modified Friedreich Ataxia Rating Scale (mFARS)
  • The Modified Friedreich Ataxia Rating Scale (mFARS) is used to assess physical functioning in patients with Friedreich’s ataxia and comprises four domains (bulbar function, upper limb coordination, lower limb coordination and postural stability). A higher score indicates greater physical impairment.
  • With regard to the analyses of the mean change in the mFARS at week 48 compared with baseline, a statistically significant difference was observed in favour of omaveloxolone compared with placebo. The 95% confidence interval for the effect size (Hedges’ g) does not lie entirely outside the non-significant range of –0.2 to 0.2; consequently, it cannot be concluded that the effect is clinically relevant.
• Morbidity – General health status as measured by the Patient Global Impression of Change (PGI-C)
  • No statistically significant differences were observed for omaveloxolone compared with placebo, either for deterioration or for improvement at week 48.
• Morbidity – Overall clinical impression using the Clinical Global Impression of Change (CGI-C)
  • The investigator’s assessment of the change in health status is not considered relevant to the patient. In general, during benefit assessment, the patient’s self-assessment of their health status is given preference over an external assessment.
• Morbidity – Activities of Daily Living (ADL)
  • No statistically significant difference was observed between the treatment arms in these measures.
• Morbidity – Fine motor skills of the upper limbs as measured by the 9-Hole Peg Test (9-HPT)
  • Fine motor function is generally considered relevant to patients in this therapeutic indication. The dossier presents data on performance speed (reciprocal value = pegs per second). No analyses are available regarding the time taken to complete the task in seconds, which are considered relevant for a meaningful and comprehensible interpretation of changes in fine motor function of the upper limbs.
• Morbidity – Functional ability of the lower limbs using the Timed 25-Foot Walk Test (T25-FWT)
  • Walking ability is fundamentally relevant to patients in this therapeutic indication. The dossier presents data on walking speed. No analyses are available regarding the time taken to complete the task in seconds, which are considered relevant for assessing changes in walking ability and for a meaningful and comprehensible interpretation of the results.
• Quality of life – Short Form (36) Health Survey (SF-36)
  • No statistically significant differences were observed between the treatment arms for either the physical or mental health summary scores of the SF-36.
• Side effects
  • No statistically significant differences were observed between the treatment arms in the overall rates of severe adverse events, serious SAE or adverse events leading to discontinuation of the study medication. Adverse events of particular interest were not pre-specified.
• Overall assessment
  • Results are available from the randomised, double-blind MOXIe Part 2 trial, which compared omaveloxolone with placebo, for the benefit assessment of omaveloxolone in the treatment of Friedreich’s ataxia in adults and adolescents aged 16 years and over.
  • No deaths occurred in either treatment arm during the study.
  • In the morbidity category, there was a statistically significant advantage of omaveloxolone compared with placebo for the endpoint of physical functioning. Based on Hedges’ g, it cannot be concluded that this effect is clinically relevant.
  • No statistically significant difference was observed for the endpoints of general health status and activities of daily living.
  • With regard to quality of life, the available data do not reveal any statistically significant differences in either the physical or mental health summary scores of the SF-36.
  • Similarly, in the area of side effects, there were no statistically significant differences in the overall rates of serious and severe adverse events, nor in the rates of therapy discontinuation due to adverse events. Adverse events of particular interest were not pre-specified.
  • In summary, no conclusions regarding the extent of the additional benefit can be drawn on the basis of the available data.

Courtesy translation only, please refer to the German original.