Journal Article

DZNE-2023-00034

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Safety of lenadogene nolparvovec gene therapy over 5 years in 189 patients with Leber hereditary optic neuropathy.

Vignal-ClermoḤ, C. ; Yu-Wai-Man, P. ; Newman, N. J. ; Carelli, V. ; Moster, M. L. ; Biousse, V. ; Subramanian, P. S. ; Wang, A.-G. ; Donahue, S. P. ; Leroy, B. P. ; Sadun, A. A. ; Klopstock, T.DZNE* ; Sergott, R. C. ; Fernández, G. R. ; Chwalisz, B. K. ; Banik, R. ; Taiel, M. ; Roux, M. ; Sahel, J.-A. ; Group, L. S. (Collaboration Author)

2023
Elsevier Science New York, NY

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Please use a persistent id in citations: doi:10.1016/j.ajo.2022.11.026

Abstract: To evaluate the safety profile of lenadogene nolparvovec (Lumevoq) in patients with Leber hereditary optic neuropathy.Pooled analysis of safety data from 5 clinical studies.A total of 189 patients received single unilateral or bilateral intravitreal injections of a recombinant adeno-associated virus 2 (rAAV2/2) vector encoding the human wild-type ND4 gene. Adverse events (AEs) were collected throughout the studies, up to 5 years. Intraocular inflammation and increased intraocular pressure (IOP) were ocular AEs of special interest. Other assessments included ocular examinations, vector bio-dissemination, and systemic immune responses against rAAV2/2.Almost all patients (95.2%) received 9 × 1010 viral genomes and 87.8% had at least 2 years of follow-up. Most patients (75.1%) experienced at least one systemic AE, but systemic treatment-related AEs occurred in 3 patients; none were serious. Intraocular inflammation was reported in 75.6% of lenadogene nolparvovec-treated eyes. Almost all intraocular inflammations occurred in the anterior chamber (58.8%) or in the vitreous (40.3%), and were of mild (90.3%) or moderate (8.8%) intensity; most resolved with topical corticosteroids alone. All IOP increases were mild to moderate in intensity. No AE led to study discontinuation. Bio-dissemination of lenadogene nolparvovec and systemic immune response were limited. The safety profile was comparable for patients treated bilaterally and unilaterally.Lenadogene nolparvovec had a good overall safety profile with excellent systemic tolerability, consistent with limited bio-dissemination. The product was well tolerated, with mostly mild ocular side effects responsive to conventional ophthalmologic treatments.

Keyword(s): Dependovirus (MeSH) ; Humans (MeSH) ; Optic Atrophy, Hereditary, Leber: drug therapy (MeSH) ; Optic Atrophy, Hereditary, Leber: genetics (MeSH) ; Genetic Vectors (MeSH) ; Parvovirinae: genetics (MeSH) ; Genetic Therapy (MeSH) ; Inflammation: etiology (MeSH) ; Leber hereditary optic neuropathy ; intravitreal gene therapy ; safety

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Contributing Institute(s):

1. Coordinator of Clinical Parkinson Research (AG Höglinger 2)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2023

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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