June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Long-term efficacy of idebenone in patients with LHON according to age at onset and disease phase: Results from the LEROS study
Author Affiliations & Notes
  • Livia Tomasso
    Chiesi Farmaceutici SpA, Parma, Emilia-Romagna, Italy
  • Valerio Carelli
    Programma di Neurogenetica, IRCCS Istituto di Scienze Neurologiche di Bologna, Bologna, Bologna, Italy
    Department of Biomedical and Neuromotor Sciences, Universita degli Studi di Bologna, Bologna, Emilia-Romagna, Italy
  • Chiara La Morgia
    Department of Biomedical and Neuromotor Sciences, Universita degli Studi di Bologna, Bologna, Emilia-Romagna, Italy
    Programma di Neurogenetica, IRCCS Istituto di Scienze Neurologiche di Bologna, Bologna, Bologna, Italy
  • Patrick Yu-Wai-Man
    John van Geest Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom
    Cambridge Eye Unit, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, United Kingdom
  • Xavier Llòria
    Chiesi Farmaceutici SpA, Parma, Emilia-Romagna, Italy
  • Thomas Klopstock
    Department of Neurology, Ludwig-Maximilians-Universitat Munchen, Munchen, Bayern, Germany
  • Footnotes
    Commercial Relationships   Livia Tomasso Chiesi Farmaceutici S.p.A., Code E (Employment); Valerio Carelli Santhera Pharmaceuticals, Chiesi GmbH, Gensight Biologics, Code C (Consultant/Contractor), Santhera Pharmaceuticals, Gensight Biologics, Code F (Financial Support), Santhera Pharmaceuticals, Chiesi GmbH, Gensight Biologics, Code R (Recipient); Chiara La Morgia Chiesi Farmaceutici S.p.A., Regulatory PharmaNet, Thenewway srl, Code C (Consultant/Contractor), Chiesi Farmaceutici S.p.A., Regulatory PharmaNet, Thenewway srl, First Class srl, Biologix, Code F (Financial Support), Chiesi Farmaceutici S.p.A., Regulatory PharmaNet, Thenewway srl, First Class srl, Biologix, Code R (Recipient); Patrick Yu-Wai-Man Santhera Pharmaceuticals, Chiesi GmbH, GenSight Biologics, Code C (Consultant/Contractor), Santhera Pharmaceuticals, GenSight Biologics, Code F (Financial Support), Santhera Pharmaceuticals, Chiesi GmbH, GenSight Biologics, Code R (Recipient); Xavier Llòria Chiesi Farmaceutici S.p.A., Code E (Employment); Thomas Klopstock Santhera Pharmaceuticals, Chiesi GmbH, GenSight Biologics, Code C (Consultant/Contractor), Santhera Pharmaceuticals, GenSight Biologics, Code F (Financial Support), Santhera Pharmaceuticals, Chiesi GmbH, GenSight Biologics, Code R (Recipient)
  • Footnotes
    Support  This study was supported by Santhera Pharmaceuticals
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1953. doi:
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      Livia Tomasso, Valerio Carelli, Chiara La Morgia, Patrick Yu-Wai-Man, Xavier Llòria, Thomas Klopstock; Long-term efficacy of idebenone in patients with LHON according to age at onset and disease phase: Results from the LEROS study. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1953.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Leber hereditary optic neuropathy (LHON) is a mitochondrial disease resulting in bilateral vision loss. Childhood-onset LHON has a relatively good prognosis, suggesting that age influences disease progression and, potentially, treatment response. In LEROS, a Phase IV, open-label interventional study (ClinicalTrials.gov NCT02774005), visual acuity (VA) outcomes following 24 months of idebenone treatment were compared to those of an external Natural History (NH) cohort. Here, we report the results of sub-analyses according to age at symptom onset and disease phase.

Methods : LEROS included patients with LHON aged ≥12 years and with a disease onset ≤5 years prior. Overall, 199 patients were enrolled, 181 of which formed the modified Intention-To-Treat (mITT) population. NH data were available from 372 patients. Patients were divided into 2 groups based on time since onset in the most recent eye: subacute/dynamic (≤1 year) and chronic (>1 year), and further stratified based on age at symptom onset: <18 years and ≥18 years. Data from the idebenone-treated group was compared to retrospective data from the NH cohort, matched by time since disease onset. Outcome measures (from baseline) were clinically relevant recovery (CRR) and clinically relevant worsening (CRW).

Results : In patients aged <18 years, VA outcomes at 24 months were observed, in treated versus untreated eyes, as follows: subacute/dynamic CRR: 31.8% (7/22) vs 59.1% (13/22), p = 0.0476; chronic CRR: 31.3% (5/16) vs 21.6% (8/37), p = 0.2406; subacute/dynamic CRW: 26.3% (5/19) vs 21.4% (3/14), p = 0.5579; chronic CRW: 8.3% (1/12) vs 19.2% (5/26), p = 0.0784. In patients aged ≥18 years, corresponding VA outcomes were observed as follows: subacute/dynamic CRR: 51.5% (51/99) vs 22.6% (12/53), p = 0.0013; chronic CRR: 32.0% (32/100) vs 12.5% (7/56), p = 0.0009; subacute/dynamic CRW: 25.7% (19/74) vs 62.9% (22/35), p = 0.0002; chronic CRW: 1.8% (1/56) vs 20.6% (7/34), p = 0.0033.

Conclusions : Idebenone improved the ratio of positive to negative VA outcomes. Treatment benefit was particularly pronounced in patients aged ≥18 years, with only non-significant positive trends observed in chronic eyes of patients aged <18 years. Results in subacute/dynamic eyes of patients aged <18 years were limited by an unusually high recovery rate in the NH cohort, warranting further study.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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