June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Visual function improvements with BIIB112 (NSR-RPGR) in X-linked retinitis pigmentosa: XIRIUS (dose-expansion) and XOLARIS (natural disease progression) studies
Author Affiliations & Notes
  • Robert E MacLaren
    Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, Oxfordshire, United Kingdom
  • Byron L Lam
    University of Miami Health System Bascom Palmer Eye Institute, Miami, Florida, United States
  • Andrew J Lotery
    University of Southampton, Southampton, United Kingdom
  • Paulo Eduardo Stanga
    Retina Service, London Vision Clinic, London, United Kingdom
    Institute of Ophthalmology, University College London, London, London, United Kingdom
  • Assad Jalil
    Manchester Royal Eye Hospital, Manchester, Manchester, United Kingdom
  • Mark E Pennesi
    Oregon Health & Science University Casey Eye Institute, Portland, Oregon, United States
  • David G Birch
    Retina Foundation of the Southwest, Dallas, Texas, United States
  • Christine Kay
    VitreoRetinal Associates PA, Gainesville, Florida, United States
  • Jiajun Liu
    Biogen Inc, Cambridge, Massachusetts, United States
  • Eileen Liao
    Biogen Inc, Cambridge, Massachusetts, United States
  • Lenore von Krusenstiern
    Biogen Inc, Cambridge, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Robert MacLaren, Biogen (F), Biogen (C), University of Oxford (P); Byron Lam, AGTC (F), Allergan, Inc. (F), Allergan, Inc. (C), Biogen, Inc. (F), Biogen, Inc. (C), Editas (F), ProQR (F), Spark Therapeutics, Inc. (F); Andrew Lotery, Biogen (S); Paulo Stanga, Apellis Canon Medical Products (F), Gyroscope (F), Iveric Bio (F), Iveric Bio (C), Keeler (F), Keeler (C), LumiThera (F), Optos Plc. (C), Optos Plc. (F), Quantel Medical (C), Quantel Medical (F), Zeiss AG (C), Zeiss AG (F); Assad Jalil, DORC (C), Novartis (C); Mark Pennesi, Adverum (C), AGTC (C), Allergan/Editas (C), Astellas Pharmaceuticals (C), Atsena (S), Biogen (C), Blue Rock (C), DTx (S), Endogena (S), Eyevensys (S), Gensight (S), Horama (S), Iveric Bio (C), Nacuity Pharmaceuticals (S), Nayan (S), Novartis (C), Ocugen (S), Ora (C), ProQR Therapeutics (S), RegenexBio (C), Roche (C), Sparing Vision (S), Vedere (S), Viewpoint Therapeutics (C); David Birch, AGTC (C), AGTC (F), Biogen (F), Editas (C), Iveric Bio (C), Nacuity (C), ProQR (C), ProQR (F), Roche-4D (F), Roche-4D (C); Christine Kay, None; Jiajun Liu, Biogen (E); Eileen Liao, Biogen (E); Lenore von Krusenstiern, Biogen (E)
  • Footnotes
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Investigative Ophthalmology & Visual Science June 2021, Vol.62, 1479. doi:
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      Robert E MacLaren, Byron L Lam, Andrew J Lotery, Paulo Eduardo Stanga, Assad Jalil, Mark E Pennesi, David G Birch, Christine Kay, Jiajun Liu, Eileen Liao, Lenore von Krusenstiern; Visual function improvements with BIIB112 (NSR-RPGR) in X-linked retinitis pigmentosa: XIRIUS (dose-expansion) and XOLARIS (natural disease progression) studies. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1479.

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

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Abstract

Purpose : X-linked retinitis pigmentosa (XLRP) is a severe phenotype of retinitis pigmentosa clinically characterized by onset of night blindness in childhood, followed by progressive vision loss that results in blindness for most individuals. BIIB112 (NSR-RPGR) is an AAV8 vector–based gene therapy that uses codon optimization to express the full-length, correctly sequenced retinitis pigmentosa GTPase regulator (RPGR) protein in the photoreceptors of individuals with XLRP caused by mutations in RPGR. Here, we present results from 2 ongoing trials in participants with XLRP: XIRIUS, a dose-expansion study of BIIB112, and XOLARIS, a natural disease progression study.

Methods : Part 1 of XIRIUS is a Phase 1, 3+3, six-dose-escalation study (NCT03116113) of BIIB112 in participants with XLRP aged ≥18 years. A subgroup of participants was identified from XOLARIS who met XIRIUS part 1 inclusion and exclusion criteria and completed 12 months of follow-up (N=69). Retinal sensitivity responder criterion was defined as an achievement of ≥7 dB improvement from baseline at ≥5 loci.

Results : Overall, 18 participants were treated with BIIB112. Treatment with the 4 highest doses (n=12) resulted in early (Month 1 responders, 6/12 [50%]) and durable (Month 12 responders, 4/12 [33%]) improvements in central retinal sensitivity. No untreated participants in XOLARIS who met the inclusion criteria for XIRIUS achieved central retinal sensitivity response (improvement of ≥7 dB at ≥5 loci) at Month 12 (33% difference in response rate between groups). Improvements in low-luminance visual acuity (LLVA), assessed by a gain of ≥15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, were observed in treated eyes in XIRIUS as early as Month 1 and through 12 months of follow-up (Month 12 proportion of participants with gain of ≥15 ETDRS letters: treated eyes, 3/11 [27%]; untreated eyes, 0/11 [0%]; one participant was missing a baseline LLVA assessment score). Most adverse events were mild and resolved, and no dose-limiting toxicities occurred at any dose. Inflammation, mostly observed at the higher doses, was successfully treated with oral corticosteroids.

Conclusions : Treatment with BIIB112 was well tolerated and, in cohorts 3-6, led to early and durable improvements in 2 measures of visual function.

This is a 2021 ARVO Annual Meeting abstract.

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