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Assessment of neurological efficacy of idebenone in pediatric patients with Friedreich's ataxia: data from a 6-month controlled study followed by a 12-month open-label extension study

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Abstract

The aim of this study was to investigate the efficacy of idebenone on neurological function as assessed by ICARS and FARS neurological rating scales in pediatric Friedreich's ataxia (FRDA) patients. Sixty-eight pediatric patients were enrolled in an open-label extension study (IONIA-E) where patients received idebenone (Catena®, 150 mg film-coated tablets) at a weight-adjusted dose of 1,350/2,250 mg/day for 12 months after patients had completed a double-blind, randomized, placebo-controlled study (IONIA) receiving either idebenone at a weight-adjusted dose of 450/900 or 1,350/2,250 mg/day or placebo for 6 months. Changes in ICARS and FARS total scores and subscores were recorded for the 12-month IONIA-E study and for the 18-month combined IONIA and IONIA-E study period. Data analyzed by a mixed-model repeated-measures ANCOVA relative to baseline resulted in least square means for the change in ICARS for the IONIA-E study of +0.98 points (SEM 0.73; p = 0.180), indicating a trend for worsening. However, combined with the IONIA study the change was −1.03 ± 0.68 points (p = 0.132), indicating a trend for improvement in neurological function over the 18-month period. Importantly, patients who received idebenone 1,350/2,250 mg/day over this period significantly improved in neurological function (change in ICARS: −3.02 ± 1.22, p = 0.014). The improvement in neurological function over time was best seen when the posture and stance subscore was excluded from the analysis. Comparable data were obtained with the FARS. The findings of the open-label IONIA-E study combined with the double-blind IONIA study indicate that idebenone at a dose of 1,350/2,250 mg/day may offer a therapeutic benefit to pediatric FRDA patients by stabilizing the overall neurological function and improving fine motor skills and speech.

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Acknowledgments

We would like to acknowledge assistance of the clinical coordinators of the study: Lisa Friedman, Erin Paulsen, Lynn Kessler, Sharaone Trifskin, and Bonnie Johnson. Statistical analyses were conducted by an independent statistician, Britt-Marie Lindström, 4Pharma, Sweden. The present study was sponsored by Santhera Pharmaceuticals. Dr. Lynch has received grant funding for other projects from the National Institutes of Health, the Muscular Dystrophy Association, the Friedreich Ataxia Research Alliance and Penwest Pharmaceuticals. Dr. Perlman has also received grant funding for other projects from the National Institutes of Health, the HighQ/CHDI Foundation, the National Ataxia Foundation, the Muscular Dystrophy Association, the Friedreich Ataxia Research Alliance, and Edison Pharmaceuticals. Drs. Meier, Coppard and Rummey are employees of Santhera Pharmaceuticals.

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Authors and Affiliations

  1. Santhera Pharmaceuticals, Liestal, Switzerland

    Thomas Meier, Christian Rummey & Nicholas J. Coppard

  2. Department of Neurology, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, CA, USA

    Susan L. Perlman

  3. Division of Neurology, The Children’s Hospital of Philadelphia, 502 Abramson Building, Philadelphia, PA, 19104-4318, USA

    David R. Lynch

Authors
  1. Thomas Meier
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  2. Susan L. Perlman
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  3. Christian Rummey
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  4. Nicholas J. Coppard
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  5. David R. Lynch
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Corresponding author

Correspondence to David R. Lynch.

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Meier, T., Perlman, S.L., Rummey, C. et al. Assessment of neurological efficacy of idebenone in pediatric patients with Friedreich's ataxia: data from a 6-month controlled study followed by a 12-month open-label extension study. J Neurol 259, 284–291 (2012). https://doi.org/10.1007/s00415-011-6174-y

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  • DOI: https://doi.org/10.1007/s00415-011-6174-y

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