Idebenon (1) – Raxone®

• Clinical trials
  • The RHODOS study was a multicentre, double-blind, randomised, placebo-controlled, parallel-group Phase II trial, which enrolled a total of 85 patients aged between 14 and 65 years with Leber’s hereditary optic neuropathy (LHON) in a 2:1 ratio.
  • The study investigated the efficacy, safety and tolerability of idebenone compared with placebo.

a) Adolescents and adult patients with Leber’s hereditary optic neuropathy (LHON)

• The G-BA classifies the extent of the additional benefit of idebenone as non-quantifiable, based on the criteria in Section 5(7) of the AM NutzenV, taking into account the severity of the condition and the therapeutic objective in treating the condition.
• There is an additional benefit, but it is non-quantifiable because the scientific evidence does not permit this.
• A key factor in the decision regarding this indication is that no advantage of idebenone over placebo could be demonstrated in terms of patient-relevant endpoints, meaning that it is not possible to quantify the additional benefit.
• mortality
  • No deaths were observed in the RHODOS study.
  • Overall, based on the available results, no conclusion can be drawn regarding the extent of the additional benefit in terms of mortality.
• Morbidity – Best improvement in visual acuity after 24 weeks
  • The ‘best improvement in visual acuity at 24 weeks’, the primary endpoint of the RHODOS study, was defined as the best improvement in visual acuity in one eye of each patient, measured as the change in logMAR between the start of the study and week 24.
  • No statistically significant difference was observed between the study arms with regard to the endpoint ‘best improvement in visual acuity at 24 weeks’.
• Morbidity – Change in best visual acuity at 24 weeks
  • The “change in best visual acuity at 24 weeks” was defined as the visual acuity of the better eye at week 24 compared with the visual acuity of the better eye at the start of the study.
  • No statistically significant difference was observed between the study arms with regard to the endpoint ‘change in best visual acuity at 24 weeks’.
• Morbidity – Change in visual acuity of the better eye (at baseline) at 24 weeks
  • The change in visual acuity of the better eye at 24 weeks was defined as the change in the eye that had the best visual acuity at the start of the study, as measured at week 24.
  • With regard to the endpoint ‘change in visual acuity of the better eye after 24 weeks’, no statistically significant difference was observed between the study arms.
  • Overall, with regard to the visual acuity endpoints, it is questionable to what extent the assessment of visual acuity in the therapeutic indication comprehensively reflects the symptoms of the condition.
• Morbidity – Change in colour contrast sensitivity after 24 weeks
  • For this endpoint, colour contrast sensitivity for the red-green (Protan) and yellow-blue (Tritan) colour pairs was assessed, but only at one study centre; consequently, results are available only for a patient population.
  • Furthermore, the analysis is based on the number of eyes. The proportion of patients showing an improvement in colour contrast sensitivity remains unclear.
  • No statistically significant difference was observed between the study arms with regard to the perception of red-green.
  • With regard to the perception of yellow-blue colours, a statistically significant advantage of idebenone compared with placebo was observed at the study centre under investigation. The estimated difference between the groups was –13.63 ± 5.05 (95% CI: [–23.61; –3.66]; p = 0.008); this was attributable to a reduction in colour confusion in the idebenone group and to an opposite change after 24 weeks in the placebo group.
  • Overall, based on the available results, no conclusion can be drawn regarding the extent of the additional benefit in terms of morbidity.
• quality of life
  • No usable data were available regarding quality of life.
• Side effects
  • No statistically significant differences in side effects were observed between the idebenone- and placebo-treated patient groups.
  • Overall, based on the available results, no conclusions can be drawn regarding the extent of the additional benefit in terms of side effects.
• Conclusion
  • Taking the available results as a whole, the G-BA arrives at the following assessment of the extent of the additional benefit: there is an additional benefit, but it is non-quantifiable, as the available scientific evidence does not currently permit a quantifiable statement on the extent of the additional benefit for patient-relevant endpoints.

Courtesy translation only, please refer to the German original.