% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Carelli:259705,
      author       = {Carelli, Valerio and Newman, Nancy J. and Yu-Wai-Man,
                      Patrick and Biousse, Valerie and Moster, Mark L. and
                      Subramanian, Prem S. and Vignal-Clermont, Catherine and
                      Wang, An-Guor and Donahue, Sean P. and Leroy, Bart P. and
                      Sergott, Robert C. and Klopstock, Thomas and Sadun, Alfredo
                      A. and Rebolleda Fernández, Gema and Chwalisz, Bart K. and
                      Banik, Rudrani and Girmens, Jean François and La Morgia,
                      Chiara and DeBusk, Adam A. and Jurkute, Neringa and
                      Priglinger, Claudia and Karanjia, Rustum and Josse, Constant
                      and Salzmann, Julie and Montestruc, François and Roux,
                      Michel and Taiel, Magali and Sahel, José-Alain and Carelli,
                      Valerio and Barboni, Piero and Carbonelli, Michele and Di
                      Vito, Lidia and Amore, Giulia and Contin, Manuela and
                      Mohamed, Susan and La Morgia, Chiara and Silvestri, Sara and
                      D’Agati, Pietro and Newman, Nancy J and Biousse, Valérie
                      and Hubbard, George Baker and O’Keefe, Ghazala and
                      Hendrick, Andrew M. and Dattilo, Michael and Peragallo,
                      Jason H. and Hawy, Eman and DuBois, Lindreth and Gibbs,
                      Deborah and Filho, Alcides Fernandes and Dobbs, Jannah and
                      Yu-Wai-Man, Patrick and Acheson, James and Boston, Hayley
                      and Eleftheriadou, Maria and Esposti, Simona and Gemenetzi,
                      Maria and Leitch-Devlin, Lauren and Tucker, William R. and
                      Jurkute, Neringa and Burale, Asma and Anand, Shweta and
                      Memon, Muhammad A. and Hussain, Rima and Jorany, Rasha and
                      Sheel, Priyansha and Moster, Mark L. and Sergott, Robert C.
                      and SantaMaria, Melissa and Tollis, Heather and DeBusk, Adam
                      A and Haller, Julia A. and Massini, Maria and Subramanian,
                      Prem S. and Pecen, Paula and Mathias, Marc and Preston, Mary
                      and Cho, Steve and Sahel, José A. and Vignal-Clermont,
                      Catherine and Girmens, Jean François and Hage, Rabih and
                      Plaine, Lise and Khemliche, Wahiba and Wang, An-Guor and
                      Cheng, Hui-Chen and Chen, Celia and Hwang, Jeong-Min and
                      Sun, Chuanbin and Donahue, Sean and Patel, Shriji and
                      Gangaputra, Sapna and Barrett, Megan and Ruark, Scott and
                      Wilkins, Saige and Leroy, Bart P. and De Zaeytijd, Julie and
                      Van Cauwenbergh, Caroline and Verhauwen, Hilde and
                      Klopstock, Thomas and Catarino, Claudia B. and Priglinger,
                      Claudia and Priglinger, Siegfried and Rudolph, Günther and
                      von Livonius Bettina, Stephan Thurau and Muth, Daniel and
                      Wolf, Armin and Al-Tamami, Jasmina and Pressler, Angelika
                      and Schertler, Cosima and Hildebrandt, Martin and Neuenhahn,
                      Michael and Sadun, Alfredo A. and Heilweil, Gad and
                      Karanjia, Rustum and Tsui, Irena and Rebolleda Fernández,
                      Gema and Urquijo, Laia Jaumendreu and Negrete Muñoz,
                      Francisco J. and Fortin, Elizabeth and Chwalisz, Bart K. and
                      Cestari, Dean and Banik, Rudrani and Tai, Katy and Castillo,
                      Lorena and Garcia, Virginia and Bandello, Antonio Morilla
                      Francesco and Barboni, Piero and Cascavilla, Maria Lucia and
                      Battista, Marco and Calcagno, Francesca and Pina, Adelaide
                      and Leruez, Stéphanie and Forooza, Rod},
      title        = {{I}ndirect {C}omparison of {L}enadogene {N}olparvovec
                      {G}ene {T}herapy {V}ersus {N}atural {H}istory in {P}atients
                      with {L}eber {H}ereditary {O}ptic {N}europathy {C}arrying
                      the $m.11778{G}\>{A}$ {MT}-{ND}4 {M}utation},
      journal      = {Ophthalmology and therapy},
      volume       = {12},
      number       = {1},
      issn         = {2193-6528},
      address      = {Heidelberg},
      publisher    = {SpringerOpen},
      reportid     = {DZNE-2023-00777},
      pages        = {401 - 429},
      year         = {2023},
      abstract     = {Lenadogene nolparvovec is a promising novel gene therapy
                      for patients with Leber hereditary optic neuropathy (LHON)
                      carrying the m.11778G>A ND4 mutation (MT-ND4). A previous
                      pooled analysis of phase 3 studies showed an improvement in
                      visual acuity of patients injected with lenadogene
                      nolparvovec compared to natural history. Here, we report
                      updated results by incorporating data from the latest phase
                      3 trial REFLECT in the pool, increasing the number of
                      treated patients from 76 to 174.The visual acuity of 174
                      MT-ND4-carrying patients with LHON injected in one or both
                      eyes with lenadogene nolparvovec from four pooled phase 3
                      studies (REVERSE, RESCUE and their long-term extension trial
                      RESTORE; and REFLECT trial) was compared to the spontaneous
                      evolution of an external control group of 208 matched
                      patients from 11 natural history studies.Treated patients
                      showed a clinically relevant and sustained improvement in
                      their visual acuity when compared to natural history. Mean
                      improvement versus natural history was - 0.30 logMAR (+ 15
                      ETDRS letters equivalent) at last observation (P < 0.01)
                      with a maximal follow-up of 3.9 years after injection. Most
                      treated eyes were on-chart as compared to less than half of
                      natural history eyes at 48 months after vision loss
                      $(89.6\%$ versus $48.1\%;$ P < 0.01) and at last observation
                      $(76.1\%$ versus $44.4\%;$ P < 0.01). When we adjusted for
                      covariates of interest (gender, age of onset, ethnicity, and
                      duration of follow-up), the estimated mean gain was - 0.43
                      logMAR (+ 21.5 ETDRS letters equivalent) versus natural
                      history at last observation (P < 0.0001). Treatment effect
                      was consistent across all phase 3 clinical trials. Analyses
                      from REFLECT suggest a larger treatment effect in patients
                      receiving bilateral injection compared to unilateral
                      injection.The efficacy of lenadogene nolparvovec in
                      improving visual acuity in MT-ND4 LHON was confirmed in a
                      large cohort of patients, compared to the spontaneous
                      natural history decline. Bilateral injection of gene therapy
                      may offer added benefits over unilateral
                      injection.NCT02652780 (REVERSE); NCT02652767 (RESCUE);
                      NCT03406104 (RESTORE); NCT03293524 (REFLECT); NCT03295071
                      (REALITY).},
      keywords     = {Gene therapy (Other) / LHON (Other) / Leber hereditary
                      optic neuropathy (Other) / MT-ND4 (Other) / Natural history
                      (Other) / Visual acuity (Other)},
      cin          = {Clinical Research (Munich)},
      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:36449262},
      pmc          = {PMC:PMC9834474},
      doi          = {10.1007/s40123-022-00611-x},
      url          = {https://pub.dzne.de/record/259705},
}