Omaveloxolon (2) – 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

• The additional benefit is not proven.
• Overall, based on the MOXIe Part 2 study, no differences relevant to the benefit assessment can be identified for the endpoint categories of mortality, morbidity, health-related quality of life and side effects.
• 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)
  • With regard to the analyses of the mean change in the mFARS total score at week 48, a statistically significant difference was observed between the treatment arms in favour of omaveloxolone. However, 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 – Activities of Daily Living using the Friedreich’s Ataxia-Activities of Daily Living (FA-ADL)
  • The dossier presents analyses of changes at week 48 based on the FA-ADL. These show no statistically significant difference between the treatment arms.
• Morbidity – frequency of falls
  • The analysis was based on the total number of falls from the start of treatment to the end of treatment, with incidence rates calculated. No statistically significant difference was observed between the treatment arms.
• Morbidity – General health status as measured by the Patient Global Impression of Change (PGI-C)
  • No statistically significant differences were observed between the treatment arms for either deterioration or improvement at week 48.
• Morbidity – Fine motor function of the upper limbs as assessed by the 9-Hole Peg Test (9-HPT)
  • Fine motor function is fundamentally relevant to patients in this therapeutic indication. The dossier presents data on performance speed (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 serious adverse events (SAEs) or of adverse events leading to discontinuation of study medication.
  • In detail, a statistically significant difference was observed for the endpoint ‘gastrointestinal disorders’, with a disadvantage for omaveloxolone. This endpoint is based on non-serious and non-severe adverse events (AEs) at the System Organ Class (SOC) level.
• Overall assessment
  • Results are available from the randomised, double-blind MOXIe Part 2 study, 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. The data allow for comparative conclusions to be drawn against the appropriate comparator therapy, best supportive care.
  • With regard to mortality, no deaths occurred in either treatment arm during the study.
  • In the category of morbidity, a statistically significant advantage in favour of omaveloxolone was observed for the endpoint of physical functioning. Based on Hedges’ g, it cannot be concluded that the effect is clinically relevant in this respect. No statistically significant difference was observed for the endpoints of activities of daily living, general health status and frequency of falls.
  • 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.
  • In the category of side effects, there were no statistically significant differences in the overall rates of serious adverse events or in the number of therapy discontinuations due to adverse events. In detail, omaveloxolone was found to be at a disadvantage for the endpoint ‘gastrointestinal disorders’ (SOC, AE). Overall, there are no differences relevant to the benefit assessment in the ‘side effects’ category.
  • Overall, based on the MOXIe Part 2 study, no differences relevant to the benefit assessment can be identified for the endpoint categories of mortality, morbidity, health-related quality of life and side effects. An additional benefit of omaveloxolone for adults and adolescents aged 16 years and over with Friedreich’s ataxia is therefore not proven.

Courtesy translation only, please refer to the German original.