Safety of Lenadogene Nolparvovec Gene Therapy Over 5 Years in 189 Patients With Leber Hereditary Optic Neuropathy

Vignal-Clermont, Catherine; Yu-Wai-Man, Patrick; Newman, Nancy J.; Carelli, Valerio; Moster, Mark L.; Biousse, Valerie; Subramanian, Prem S.; Wang, An-Guor; Donahue, Sean P.; Leroy, Bart P.; Sadun, Alfredo A.; Klopstock, Thomas; Sergott, Robert C.; Fernandez, Gema Rebolleda; Chwalisz, Bart K.; Banik, Rudrani; Taiel, Magali; Roux, Michel und Sahel, Jose-Alain (2023): Safety of Lenadogene Nolparvovec Gene Therapy Over 5 Years in 189 Patients With Leber Hereditary Optic Neuropathy. In: American Journal of Ophthalmology, Bd. 249: S. 108-125

Abstract

PURPOSE: To evaluate the safety profile of lenadogene nolparvovec (Lumevoq) in patients with Leber hereditary optic neuropathy. center dot DESIGN: Pooled analysis of safety data from 5 clinical studies. center dot METHODS: A total of 189 patients received single unilateral or bilateral intravitreal injections of a recom-binant adeno-associated virus 2 (rAAV2/2) vector en-coding 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.center dot RESULTS: Almost all patients (95.2%) received 9 x 10 10 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. Intraocu-lar inflammation was reported in 75.6% of lenadogene nolparvovec-treated eyes. Almost all intraocular inflam-mations occurred in the anterior chamber (58.8%) or in the vitreous (40.3%), and were of mild (90.3%) or mod-erate (8.8%) intensity;most resolved with topical corti-costeroids 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 unilater-ally.center dot CONCLUSIONS: 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. (Am J Ophthalmol 2023;249: 108-125. (c) 2022 Else-vier Inc. All rights reserved.)

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198