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@ARTICLE{VignalClermo:169155,
      author       = {Vignal-ClermoḤ, Catherine and Yu-Wai-Man, Patrick and
                      Newman, Nancy J and Carelli, Valerio and Moster, Mark L and
                      Biousse, Valerie and Subramanian, Prem S and Wang, An-Guor
                      and Donahue, Sean P and Leroy, Bart P and Sadun, Alfredo A
                      and Klopstock, Thomas and Sergott, Robert C and Fernández,
                      Gema Rebolleda and Chwalisz, Bart K and Banik, Rudrani and
                      Taiel, Magali and Roux, Michel and Sahel, José-Alain},
      collaboration = {Group, LHON Study},
      title        = {{S}afety of lenadogene nolparvovec gene therapy over 5
                      years in 189 patients with {L}eber hereditary optic
                      neuropathy.},
      journal      = {American journal of ophthalmology},
      volume       = {249},
      issn         = {0002-9394},
      address      = {New York, NY},
      publisher    = {Elsevier Science},
      reportid     = {DZNE-2023-00034},
      pages        = {108 - 125},
      year         = {2023},
      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.},
      keywords     = {Dependovirus / Humans / Optic Atrophy, Hereditary, Leber:
                      drug therapy / Optic Atrophy, Hereditary, Leber: genetics /
                      Genetic Vectors / Parvovirinae: genetics / Genetic Therapy /
                      Inflammation: etiology / Leber hereditary optic neuropathy
                      (Other) / intravitreal gene therapy (Other) / safety
                      (Other)},
      cin          = {AG Höglinger 2},
      ddc          = {610},
      cid          = {I:(DE-2719)1111015},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36496192},
      doi          = {10.1016/j.ajo.2022.11.026},
      url          = {https://pub.dzne.de/record/169155},
}