TY - JOUR
T1 - Three‐Year Safety Results of SAR422459 (EIAV‐ABCA4) Gene Therapy in Patients With ABCA4‐Associated Stargardt Disease
T2 - An Open‐Label Dose‐Escalation Phase I/IIa Clinical Trial, Cohorts 1‐5: Results of Gene Therapy in Patients With Stargardt Disease
AU - Parker, Maria A.
AU - Erker, Laura R.
AU - Audo, Isabelle
AU - Choi, Dongseok
AU - Mohand-Said, Saddek
AU - Sestakauskas, Kastytis
AU - Benoit, Patrick
AU - Appelqvist, Terence
AU - Krahmer, Melissa
AU - Ségaut-Prévost, Caroline
AU - Lujan, Brandon J.
AU - Faridi, Ambar
AU - Chegarnov, Elvira N.
AU - Steinkamp, Peter N.
AU - Ku, Cristy
AU - da Palma, Mariana Matioli
AU - Barale, Pierre Olivier
AU - Ayelo-Scheer, Sarah
AU - Lauer, Andreas
AU - Stout, Tim
AU - Wilson, David J.
AU - Weleber, Richard G.
AU - Pennesi, Mark E.
AU - Sahel, José Alain
AU - Yang, Paul
N1 - Publisher Copyright:
© 2022 The Author(s)
PY - 2022/8
Y1 - 2022/8
N2 - Purpose: To report on the safety of the first 5 cohorts of a gene therapy trial using recombinant equine infectious anemia virus expressing ABCA4 (EIAV-ABCA4) in adults with Stargardt dystrophy due to mutations in ABCA4. Design: Nonrandomized multicenter phase I/IIa clinical trial. Methods: Patients received a subretinal injection of EIAVABCA4 in the worse-seeing eye at 3 dose levels and were followed for 3 years after treatment. Main outcome measures: The primary end point was ocular and systemic adverse events. The secondary end points were best-corrected visual acuity, static perimetry, kinetic perimetry, total field hill of vision, full field electroretinogram, multifocal ERG, color fundus photography, short-wavelength fundus autofluorescence, and spectral domain optical coherence tomography. Results: The subretinal injections were well tolerated by all 22 patients across 3 dose levels. There was 1 case of a treatment-related ophthalmic serious adverse event in the form of chronic ocular hypertension. The most common adverse events were associated with the surgical procedure. In 1 patient treated with the highest dose, there was a significant decline in the number of macular flecks as compared with the untreated eye. However, in 6 patients, hypoautofluorescent changes were worse in the treated eye than in the untreated eye. Of these, 1 patient had retinal pigment epithelium atrophy that was characteristic of tissue damage likely associated with bleb induction. No patients had any clinically significant changes in best-corrected visual acuity, static perimetry, kinetic perimetry, total field hill of vision, full field electroretinogram, or multifocal ERG attributable to the treatment. Conclusions: Subretinal treatment with EIAV-ABCA4 was well tolerated with only 1 case of ocular hypertension. No clinically significant changes in visual function tests were found to be attributable to the treatment. However, 27% of treated eyes showed exacerbation of retinal pigment epithelium atrophy on fundus autofluorescence. There was a significant reduction in macular flecks in 1 treated eye from the highest dose cohort. Additional follow-up and continued investigation in more patients will be required to fully characterize the safety and efficacy of EIAV-ABCA4.
AB - Purpose: To report on the safety of the first 5 cohorts of a gene therapy trial using recombinant equine infectious anemia virus expressing ABCA4 (EIAV-ABCA4) in adults with Stargardt dystrophy due to mutations in ABCA4. Design: Nonrandomized multicenter phase I/IIa clinical trial. Methods: Patients received a subretinal injection of EIAVABCA4 in the worse-seeing eye at 3 dose levels and were followed for 3 years after treatment. Main outcome measures: The primary end point was ocular and systemic adverse events. The secondary end points were best-corrected visual acuity, static perimetry, kinetic perimetry, total field hill of vision, full field electroretinogram, multifocal ERG, color fundus photography, short-wavelength fundus autofluorescence, and spectral domain optical coherence tomography. Results: The subretinal injections were well tolerated by all 22 patients across 3 dose levels. There was 1 case of a treatment-related ophthalmic serious adverse event in the form of chronic ocular hypertension. The most common adverse events were associated with the surgical procedure. In 1 patient treated with the highest dose, there was a significant decline in the number of macular flecks as compared with the untreated eye. However, in 6 patients, hypoautofluorescent changes were worse in the treated eye than in the untreated eye. Of these, 1 patient had retinal pigment epithelium atrophy that was characteristic of tissue damage likely associated with bleb induction. No patients had any clinically significant changes in best-corrected visual acuity, static perimetry, kinetic perimetry, total field hill of vision, full field electroretinogram, or multifocal ERG attributable to the treatment. Conclusions: Subretinal treatment with EIAV-ABCA4 was well tolerated with only 1 case of ocular hypertension. No clinically significant changes in visual function tests were found to be attributable to the treatment. However, 27% of treated eyes showed exacerbation of retinal pigment epithelium atrophy on fundus autofluorescence. There was a significant reduction in macular flecks in 1 treated eye from the highest dose cohort. Additional follow-up and continued investigation in more patients will be required to fully characterize the safety and efficacy of EIAV-ABCA4.
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U2 - 10.1016/j.ajo.2022.02.013
DO - 10.1016/j.ajo.2022.02.013
M3 - Article
C2 - 35248547
AN - SCOPUS:85130623458
SN - 0002-9394
VL - 240
SP - 285
EP - 301
JO - American journal of ophthalmology
JF - American journal of ophthalmology
ER -