June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Safety and efficacy of sepofarsen in the second treated eye in a Ph1b/2 extension trial in Leber Congenital Amaurosis type 10 (LCA10)
Author Affiliations & Notes
  • Stephen R Russell
    Department of Ophthalmology and Visual Sciences, Institute for Vision Research, Carver School of Medicine, University of Iowa, Iowa City, Iowa, United States
  • Arlene V Drack
    Department of Ophthalmology and Visual Sciences, Institute for Vision Research, Carver School of Medicine, University of Iowa, Iowa City, Iowa, United States
  • Artur V Cideciyan
    Department of Ophthalmology and Visual Sciences, Scheie Eye Institute, Philadelphia, Pennsylvania, United States
    Department of Ophthalmology and Visual Sciences, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Samuel G Jacobson
    Department of Ophthalmology and Visual Sciences, Scheie Eye Institute, Philadelphia, Pennsylvania, United States
    Department of Ophthalmology and Visual Sciences, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Bart Leroy
    Department of Ophthalmology & Center for Medical Genetics, Ghent University Hospital & Ghent University, Ghent, Belgium
    Ophthalmic Genetics & Visual Electrophysiology, Division of Ophthalmology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • Allen Ho
    Department of Ophthalmology, Wills Eye Hospital, Philadelphia, Pennsylvania, United States
  • Caroline Van Cauwenbergh
    Department of Ophthalmology & Center for Medical Genetics, Ghent University Hospital & Ghent University, Ghent, Belgium
  • Arun kumar Krishnan
    Department of Ophthalmology and Visual Sciences, Scheie Eye Institute, Philadelphia, Pennsylvania, United States
    Department of Ophthalmology and Visual Sciences, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Wilhelmina R. den Hollender
    ProQR Therapeutics NV, Leiden, Zuid-Holland, Netherlands
  • Adriana Hollestein-Havelaar
    ProQR Therapeutics NV, Leiden, Zuid-Holland, Netherlands
  • Mike Schwartz
    ProQR Therapeutics NV, Leiden, Zuid-Holland, Netherlands
  • Aniz Girach
    ProQR Therapeutics NV, Leiden, Zuid-Holland, Netherlands
  • Footnotes
    Commercial Relationships   Stephen Russell, Digital Diagnostics (I), Novartis (C), ProQR Therapeutics (F), Spark Therapeutics (F); Arlene Drack, ProQR Therapeutics (F); Artur Cideciyan, ProQR Therapeutics (F); Samuel Jacobson, ProQR Therapeutics (F); Bart Leroy, ProQR Therapeutics (F); Allen Ho, ProQR Therapeutics (F); Caroline Van Cauwenbergh, ProQR Therapeutics (F); Arun Krishnan, ProQR Therapeutics (F); Wilhelmina den Hollender, ProQR Therapeutics (E); Adriana Hollestein-Havelaar, ProQR Therapeutics (E); Mike Schwartz, ProQR Therapeutics (E); Aniz Girach, ProQR Therapeutics (E)
  • Footnotes
    Support  ProQR Therapeutics
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 3317. doi:
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      Stephen R Russell, Arlene V Drack, Artur V Cideciyan, Samuel G Jacobson, Bart Leroy, Allen Ho, Caroline Van Cauwenbergh, Arun kumar Krishnan, Wilhelmina R. den Hollender, Adriana Hollestein-Havelaar, Mike Schwartz, Aniz Girach; Safety and efficacy of sepofarsen in the second treated eye in a Ph1b/2 extension trial in Leber Congenital Amaurosis type 10 (LCA10). Invest. Ophthalmol. Vis. Sci. 2021;62(8):3317.

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

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Abstract

Purpose : LCA10 is a severe, degenerative inherited retinal disease resulting in childhood blindness, which has no treatment. Sepofarsen is an intravitreal RNA antisense oligonucleotide which showed clinically meaningful results following unilateral injection in a Ph1b/2 trial for LCA10 due to the c.2991+1655A>G mutation in the CEP290 gene. Safety and efficacy of sepofarsen dosed in the second eye was evaluated in the extension trial (Insight; NCT03913130).

Methods : Patients who completed the Ph1b/2 trial, multicenter, open-label, multiple-dose escalation sepofarsen trial were given the opportunity to enroll into the extension trial for continued dosing in their first treated eye as well as initiation of treatment in their second eye with the 160/80µg loading/maintenance dose, using a 6-monthly dosing interval. Nine out of 11 patients from the Ph1b/2 trial enrolled in the extension trial. As main efficacy parameters, change in Best-Corrected Visual Acuity (BCVA) and Full-Field Stimulus Test (FST) were assessed.

Results : At data cut-off in July 2020, 4 patients aged 15–45 years had received 1 intravitreal injection of sepofarsen in their second eye and had completed a 3- or 6-month visit. One patient developed cataract at Month 9 in the second treated eye. No other safety findings were reported. Meaningful BCVA improvements (>-0.8 logMAR) were reported in the second treated eye for 2 of the 4 patients, similar to the improvements observed in their first treated eye. All 4 patients showed a FST improvement ranging from -0.74 to -2.35 log cd/m2, generally similar to the FST responses observed in their first treated eyes.

Conclusions : This data analysis strongly corroborates the clinically meaningful vision improvements and safety profile observed in the Ph1b/2 trial. Second eye responses to sepofarsen parallel the first eye treated responses both in visual acuity and retinal sensitivity (FST) improvements. Sepofarsen safety profile for the 160/80µg dose group in this extension trial is consistent with that observed in the Ph1b/2 trial. Further analyses on this ongoing extension trial and the Ph2/3 trial (Illuminate; NCT03913143) are expected.

This is a 2021 ARVO Annual Meeting abstract.

 

Figure. Change in Best Corrected Visual Acuity (BCVA; logMAR) and Full-Field stimulus test (FST; log cd/m2) from baseline to 3 months post dosing in the first eye and the second eye treated

Figure. Change in Best Corrected Visual Acuity (BCVA; logMAR) and Full-Field stimulus test (FST; log cd/m2) from baseline to 3 months post dosing in the first eye and the second eye treated

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