June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Safety Profile of the Surgical Procedure for the Administration of Ocular Gene Therapies
Author Affiliations & Notes
  • Ronald BUGGAGE
    Sanofi, Chilly-Mazarin, France
  • Pierre-Olivier Barale
    Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, Paris, France
    DHU Sight Restore INSERM-DHOS CIC 1423, Paris, France
  • Sarah Ayello-Scheer
    Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, Paris, France
    DHU Sight Restore INSERM-DHOS CIC 1423, Paris, France
  • Andreas K Lauer
    Casey Eye Institute, Oregon Health & Sciences University, Portland, Oregon, United States
  • Tim Stout
    Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, United States
  • Isabelle S Audo
    Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, Paris, France
    DHU Sight Restore INSERM-DHOS CIC 1423, Paris, France
  • Saddek Mohand-Said
    Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, Paris, France
    Sorbonne Universités, UPMC Université Paris 06, Inserm UMRS 968,CNRS, Institut de la Vision, Paris, France
  • Jose Alain Sahel
    Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, Paris, France
    Sorbonne Universités, UPMC Université Paris 06, Inserm UMRS 968,CNRS, Institut de la Vision, Paris, France
  • Paul Yang
    Casey Eye Institute, Oregon Health & Sciences University, Portland, Oregon, United States
  • Mark E Pennesi
    Casey Eye Institute, Oregon Health & Sciences University, Portland, Oregon, United States
  • Richard G Weleber
    Casey Eye Institute, Oregon Health & Sciences University, Portland, Oregon, United States
  • Laurence Titeux
    Sanofi, Chilly-Mazarin, France
  • Amel Lahmar
    Sanofi, Chilly-Mazarin, France
  • Preethi A Sundaram
    Sanofi, Chilly-Mazarin, France
  • Footnotes
    Commercial Relationships   Ronald BUGGAGE, Sanofi (E); Pierre-Olivier Barale , None; Sarah Ayello-Scheer , None; Andreas Lauer, Oxford BioMedica (F), Sanofi-Fovea (F); Tim Stout, Oxford BioMedica (C), Sanofi (C); Isabelle Audo, None; Saddek Mohand-Said, None; Jose Sahel, None; Paul Yang, None; Mark Pennesi, Sanofi (S); Richard Weleber, Sanofi (F); Laurence Titeux, Sanofi (E); Amel Lahmar, Sanofi (E); Preethi Sundaram, Sanofi (E)
  • Footnotes
    Support  Casey Eye Institute: unrestricted grant from Research to Prevent Blindness
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1491. doi:
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      Ronald BUGGAGE, Pierre-Olivier Barale, Sarah Ayello-Scheer, Andreas K Lauer, Tim Stout, Isabelle S Audo, Saddek Mohand-Said, Jose Alain Sahel, Paul Yang, Mark E Pennesi, Richard G Weleber, Laurence Titeux, Amel Lahmar, Preethi A Sundaram; Safety Profile of the Surgical Procedure for the Administration of Ocular Gene Therapies. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1491.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To characterize the safety profile of the surgical procedure including vitrectomy followed by a subretinal injection used to administer lentiviral gene therapies to patients with Stargardt Macular Degeneration (SMD) and retinitis pigmentosa (RP) associated with Usher Syndrome, Type 1B (USH1B).

Methods :
All reported adverse events (AEs) including descriptions of event severity, relatedness to surgery or the investigational medicinal product (IMP), and preferred term per the MedDRA dictionary were collected from two ongoing 48-week dose-escalation Phase I/II clinical trials investigating the safety and tolerability of SAR422459 (an ABCA4 gene replacement therapy for SMD; NCT01367444) and SAR421869 (a MYO7A gene replacement therapy for USH1B; NCT01505062) administered to the subretinal space by subretinal injection.

Results : As of 9 November 2016, 20/23 patients with end-stage SMD and 8/9 patients with advanced RP have received SAR422459 and SAR421869, respectively via subretinal injection in the worse eye, and experienced at least 1 AE. Of the total 190 reported AEs, including 4 serious AEs, from the two studies 106: (56%) were related to the surgery only, 6 (3%) to the IMP only and 21 (11%) to both the surgery and IMP. The vast majority, 115 (91%) of the surgery related AEs were mild in severity and 119 (94%) were reported within 4 weeks of the procedure. The most frequent surgery related AEs were conjunctival hemorrhage (12%), increased intraocular pressure (IOP) (11%), eye pain (7%), eye pruritus, subretinal fluid, and retinal hemorrhage (6%) and decreased IOP (5%). Of the 4 reported SAEs in 4 patients, 2 (uveitis, reduced visual acuity) were related to the surgery and the IMP, 1 (uveitis) to the IMP only and 1 (elevated IOP) to the surgery only.

Conclusions : The 1-year surgery related AEs from these two studies demonstrates that the safety profile for events related only to the surgical procedure is acceptable and raises no particular safety concerns beyond those associated with other vitreoretinal surgeries. The occurrence of uveitis in 2 patients has helped to refine the postoperative management of inflammation in the trials. Our experience indicates that the establishment of surgical standards for the perioperative care of patients receiving gene therapies administered by subretinal injection will be particularly important to insure the safe delivery of such treatments.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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