Observational Study

. 2024 Jan 17;14(1):122.

doi: 10.3390/biom14010122.

Real-World Safety and Effectiveness of Voretigene Neparvovec: Results up to 2 Years from the Prospective, Registry-Based PERCEIVE Study

M Dominik Fischer^{1

2

3}, Francesca Simonelli⁴, Jayashree Sahni⁵, Frank G Holz⁶, Rainer Maier⁵, Christina Fasser⁷, Andrea Suhner⁵, Daniel P Stiehl⁵, Bee Chen⁸, Isabelle Audo^{9

10}, Bart P Leroy^{11

12}; PERCEIVE Study Group

Collaborators, Affiliations

Collaborators

PERCEIVE Study Group:
Arif O Khan, Martin Charles, Jose Domingo Luna, John Grigg, Markus Ritter, Rupert Wolfgang Strauss, Alexander Oscar, Juliana Sallum, Fernanda Porto, Christian Pruente, Petra Liskova, Siegfried Georg Priglinger, Christoph Friedburg, Line Kessel, Jaume Català-Mora, Pilar Tejada Palacios, Luis Arias, Cristina Irigoyen Laborra, Enrique Rodríguez-de-la-Rúa, Eric Souied, Michel Weber, Hélène Dollfus, D Bremond-Gignac, Robert H Henderson, James Bainbridge, Assad Jalil, Mirjana Bjeloš, Edit Tóth-Molnár, Zoltan Z Nagy, Eyal Banin, Miriam Ehrenberg, Fabrizio Giansanti, Stanislao Rizzo, Leonardo Colombo, L. Ingeborgh van den Born, Carel B Hoyng, C J F Boon, Josephine Prener Holtan, Marcin Stopa, João Pedro Marques, Beata Busanyova, Ulrika Kjellström, Madeleine Zetterberg, Anibal Francone, Gramajo A L, Muhlberger T, Natalia Labat, Saucedo Matías Sebastián, Claudio Patricio Juarez, Caio Henrique Marques Texeira, Mylene Matsuhara, Agostini Rafael, Marie Vajter, Birgit Lorenz, Philipp Herrmann, Sandrine H Künzel, Enrique Jiménez, Cristina López López, J A Reche-Sainz, Almudena de-Pablo-Cabrera, Ana Ortueta-Olartecoechea, Ana Maria Dorado, Leire Juaristi Eizmendi, Migual Ruiz, Iraia Reparaz Bonilla, Matthieu Robert, Alejandra Daruich, Yannik Laich, Serena Zaman, Michel Michaelides, Robert E MacLaren, Tsveta Ivanova, Tareq Jaouni, Edward Averbukh, Devora Marks Ohana, Iris Deitch, Valentina Di Iorio, Settimio Rossi, Michele Della Corte, Paolo Melillo, Francesco Testa, Koen A van Overdam, Joeri De Hoog, H. Stevie Tan, Ragnheidur Bragadottir, Ragnhild W Jansson, Maciej Robert Krawczyński, Zuzanna Niedziela-Schwartz, João P Figueira, Mário Alfaiate, Monika Gromová, Lotta Gränse, Sten Andréasson, Marcus von Knorring, Joakim Thylefors

Affiliations

¹ Centre for Ophthalmology, University of Tübingen, 72076 Tübingen, Germany.
² Oxford Eye Hospital, Oxford University NHS Foundation Trust, Oxford OX3 9DU, UK.
³ Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
⁴ Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Via S. Pansini, 5, 80131 Napoli, Italy.
⁵ Novartis Pharma AG, 4056 Basel, Switzerland.
⁶ Department of Ophthalmology, University of Bonn, Ernst-Abbe-Straße 2, 53127 Bonn, Germany.
⁷ Retina International, D02 TW98 Dublin, Ireland; Retina Suisse, 8005 Zürich, Switzerland.
⁸ Novartis Pharmaceutical Corporation, East Hanover, NJ 7936, USA.
⁹ Sorbonne Université, INSERM, CNRS, Institut de la Vision, 75012 Paris, France.
¹⁰ 15-20 Hôpital National de la Vision, National Rare Disease Center REFERET, INSERM-DGOS CIC1423, 75012 Paris, France.
¹¹ Department of Ophthalmology & Center for Medical Genetics Ghent, Ghent University & Ghent University Hospital, 9000 Ghent, Belgium.
¹² Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

PMID: 38254722
PMCID: PMC10813228
DOI: 10.3390/biom14010122

Observational Study

Real-World Safety and Effectiveness of Voretigene Neparvovec: Results up to 2 Years from the Prospective, Registry-Based PERCEIVE Study

M Dominik Fischer et al. Biomolecules. 2024.

. 2024 Jan 17;14(1):122.

doi: 10.3390/biom14010122.

Authors

Collaborators

PERCEIVE Study Group:
Arif O Khan, Martin Charles, Jose Domingo Luna, John Grigg, Markus Ritter, Rupert Wolfgang Strauss, Alexander Oscar, Juliana Sallum, Fernanda Porto, Christian Pruente, Petra Liskova, Siegfried Georg Priglinger, Christoph Friedburg, Line Kessel, Jaume Català-Mora, Pilar Tejada Palacios, Luis Arias, Cristina Irigoyen Laborra, Enrique Rodríguez-de-la-Rúa, Eric Souied, Michel Weber, Hélène Dollfus, D Bremond-Gignac, Robert H Henderson, James Bainbridge, Assad Jalil, Mirjana Bjeloš, Edit Tóth-Molnár, Zoltan Z Nagy, Eyal Banin, Miriam Ehrenberg, Fabrizio Giansanti, Stanislao Rizzo, Leonardo Colombo, L. Ingeborgh van den Born, Carel B Hoyng, C J F Boon, Josephine Prener Holtan, Marcin Stopa, João Pedro Marques, Beata Busanyova, Ulrika Kjellström, Madeleine Zetterberg, Anibal Francone, Gramajo A L, Muhlberger T, Natalia Labat, Saucedo Matías Sebastián, Claudio Patricio Juarez, Caio Henrique Marques Texeira, Mylene Matsuhara, Agostini Rafael, Marie Vajter, Birgit Lorenz, Philipp Herrmann, Sandrine H Künzel, Enrique Jiménez, Cristina López López, J A Reche-Sainz, Almudena de-Pablo-Cabrera, Ana Ortueta-Olartecoechea, Ana Maria Dorado, Leire Juaristi Eizmendi, Migual Ruiz, Iraia Reparaz Bonilla, Matthieu Robert, Alejandra Daruich, Yannik Laich, Serena Zaman, Michel Michaelides, Robert E MacLaren, Tsveta Ivanova, Tareq Jaouni, Edward Averbukh, Devora Marks Ohana, Iris Deitch, Valentina Di Iorio, Settimio Rossi, Michele Della Corte, Paolo Melillo, Francesco Testa, Koen A van Overdam, Joeri De Hoog, H. Stevie Tan, Ragnheidur Bragadottir, Ragnhild W Jansson, Maciej Robert Krawczyński, Zuzanna Niedziela-Schwartz, João P Figueira, Mário Alfaiate, Monika Gromová, Lotta Gränse, Sten Andréasson, Marcus von Knorring, Joakim Thylefors

Affiliations

¹ Centre for Ophthalmology, University of Tübingen, 72076 Tübingen, Germany.
² Oxford Eye Hospital, Oxford University NHS Foundation Trust, Oxford OX3 9DU, UK.
³ Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
⁴ Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Via S. Pansini, 5, 80131 Napoli, Italy.
⁵ Novartis Pharma AG, 4056 Basel, Switzerland.
⁶ Department of Ophthalmology, University of Bonn, Ernst-Abbe-Straße 2, 53127 Bonn, Germany.
⁷ Retina International, D02 TW98 Dublin, Ireland; Retina Suisse, 8005 Zürich, Switzerland.
⁸ Novartis Pharmaceutical Corporation, East Hanover, NJ 7936, USA.
⁹ Sorbonne Université, INSERM, CNRS, Institut de la Vision, 75012 Paris, France.
¹⁰ 15-20 Hôpital National de la Vision, National Rare Disease Center REFERET, INSERM-DGOS CIC1423, 75012 Paris, France.
¹¹ Department of Ophthalmology & Center for Medical Genetics Ghent, Ghent University & Ghent University Hospital, 9000 Ghent, Belgium.
¹² Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

PMID: 38254722
PMCID: PMC10813228
DOI: 10.3390/biom14010122

Abstract

Voretigene neparvovec (VN) is the first available gene therapy for patients with biallelic RPE65-mediated inherited retinal dystrophy who have sufficient viable retinal cells. PERCEIVE is an ongoing, post-authorization, prospective, multicenter, registry-based observational study and is the largest study assessing the real-world, long-term safety and effectiveness of VN. Here, we present the outcomes of 103 patients treated with VN according to local prescribing information. The mean (SD) age was 19.5 (10.85) years, 52 (50.5%) were female, and the mean (SD) duration of the follow up was 0.8 (0.64) years (maximum: 2.3 years). Thirty-five patients (34%) experienced ocular treatment-emergent adverse events (TEAEs), most frequently related to chorioretinal atrophy (n = 13 [12.6%]). Eighteen patients (17.5%; 24 eyes [13.1%]) experienced ocular TEAEs of special interest, including intraocular inflammation and/or infection related to the procedure (n = 7). The mean (SD) changes from baseline in full-field light-sensitivity threshold testing (white light) at month 1, month 6, year 1, and year 2 were -16.59 (13.48) dB (51 eyes), -18.24 (14.62) dB (42 eyes), -15.84 (14.10) dB (10 eyes), and -13.67 (22.62) dB (13 eyes), respectively. The change in visual acuity from baseline was not clinically significant. Overall, the outcomes of the PERCEIVE study are consistent with the findings of VN pivotal clinical trials.

Trial registration: ClinicalTrials.gov NCT00516477 NCT01208389 NCT00999609.

Keywords: RPE65-associated inherited retinal dystrophies; effectiveness; real world; safety; voretigene neparvovec.

© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest. M.D.F. reports consulting fees from Adelphi Values, Advent France Biotechnology, Adverum, Alphasights, Arctos Medical, Atheneum, Atsena, Axiom Healthcare Strategies, Bayer, Biogen, Cambridge Consultants, Decision Resources, Dialectica, Frontera Therapeutics, Hoffmann Eitle, Janssen Research and Development, MedScape, Mogrify, Navigant, Novartis, Oxford Medical Group, PeerVoice, Physicians Education Resource, Roche, RegenxBio, Sirion, Sovinnova Partners, Sparing Vision, STZeyetrial, System Analytic, Techspert, and Vindico Medical Education. He is not employed by Novartis, has no intellectual property rights, and/or financial interest in Luxturna. F.S. reports consulting fees from 3P solution, Acucela Inc., AIM group, Alia therapeutics, Allergan, AAVantgarde Bio, Bayer, Biogen, Iveric Bio, K-link SH, Kodiak, Maprovider, MeiraGTx, Novartis, Omikron, ProQR therapeutics, Santhera, SIFI, and Uvet. She is not employed by Novartis, has no intellectual property rights, and/or financial interest in Luxturna. F.G.H. reports research grants and consulting fees from Acucela, Allergan, Apellis, Bayer, Bioeq/Formycon, Roche/Genentech, Geuder, Heidelberg Engineering, ivericBio, Pixium Vision, Novartis, Zeiss; consulting fees from Alexion, Alzheon, Annexon, Astellas, Boehringer-Ingelheim, Cirrus, Grayburg Vision, LinBioscience, Stealth BioTherapeutics, Aerie, and Oxurion. R.M. and J.S. are employees of Novartis Pharma AG, Basel, Switzerland. B.C. is an employee of Novartis Pharmaceutical Corporation, USA. A.S. and D.P.S. were employees of Novartis Pharma AG when the year 2 analyses were conducted. A.S and D.P.S. are current employees of Tenpoint Therapeutics and UCB Farchim SA, respectively. C.F. is the former President of Retina International, who received unrestricted educational grants from Novartis, Roche, Biogen, Apellis, Spark Therapeutics, Inc., ProQR Therapeutics, and GenSight Biologics; reports the consulting fee from Apellis Pharmaceuticals, Inc; and is a member of advisory boards in Novartis and Hoffmann-La Roche. I.A. reports consulting fees from Novartis, ProQR Therapeutics, Roche, and 4D Molecular Therapeutics. B.P.L. reports consulting fees from 4D Molecular Therapeutics, AAVgardeBio, Akouos, Alia Therapeutics, Atsena Therapeutics, Bayer, Biogen, GenSight Biologics, Iveric Bio, Jansen Pharmaceuticals (J&J), Novartis, Opus Genetics, Oxurion, ProQR Therapeutics, RegenXBio, Santen, Spark Therapeutics, Inc, Transine Therapeutics, Vedere Bio, and ViGeneron, and travel support from GenSight Therapeutics, Iveric Bio, Novartis, and ProQR Therapeutics.

Figures

**Figure 1**
Mean change from baseline in FST (white light) up to 2 years after VN administration in all patients, patients aged <18 years and those aged ≥18 years. dB, decibel; FST, full-field light-sensitivity threshold testing; n, number of eyes; VN, voretigene neparvovec. Baseline data were available for 127 eyes. Error bars represent SD.

**Figure 2**
Mean change from baseline in VA (LogMAR) up to 2 years after receiving VN in all patients, patients aged <18 years, and those aged ≥18 years. VA, visual acuity; LogMAR, logarithm of the minimum angle of resolution; n, number of eyes; VN, voretigene neparvovec. Baseline data were available for 148 eyes. Error bars represent SD.

**Figure 3**
Mean change from baseline in foveal thickness (µm; Heidelberg Spectralis OCT) up to 2 years after VN therapy in all patients, patients aged <18 years, and those aged ≥18 years. n, number of eyes; VN, voretigene neparvovec. Baseline data were available for 117 eyes. Error bars represent SD.

**Figure 4**
Mean change in FST (white light) from baseline in patients with CRAs versus those without CRAs. BL, baseline; dB, decibel; CRA, chorioretinal atrophy; FST, full-field light-sensitivity threshold testing; n, number of eyes. Baseline data are available for 15 eyes with CRAs and 112 eyes without CRAs. Error bars indicate SD.

**Figure 5**
Mean change in VA (LogMAR) from baseline in patients with CRAs versus those without CRAs. VA, visual acuity; BL, baseline; CRA, chorioretinal atrophy; LogMAR, logarithm of minimum angle of resolution; n, number of eyes. Baseline data are available for 19 eyes with CRAs and 129 eyes without CRAs. Error bars indicate SD.

See this image and copyright information in PMC

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Real-World Safety and Effectiveness of Voretigene Neparvovec: Results up to 2 Years from the Prospective, Registry-Based PERCEIVE Study

Collaborators

Affiliations

Real-World Safety and Effectiveness of Voretigene Neparvovec: Results up to 2 Years from the Prospective, Registry-Based PERCEIVE Study

Authors

Collaborators

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Abstract

Conflict of interest statement

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