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French company GenSight Biologics announces positive results for its Phase I/II clinical study of a gene therapy treatment for Leber Hereditary Optic Neuropathy

GenSight Biologics S.A. (Euronext: SIGHT) has announced the publication of the company’s clinical results from a Phase I/II study and long-term follow-up of an experimental gene therapy, ”GS010”, designed for the treatment of Leber Hereditary Optic Neuropathy (LHON). According to the company, the study demonstrated that GS010 (rAAV2/2-ND4) was safe and well tolerated 2 years after a single unilateral intravitreal administration. A full report, entitled “Safety of rAAV2/2-ND4 Gene Therapy for Leber Hereditary Optic Neuropathy, is available in the journal Ophthalmology.


According to GenSight, the novel gene therapy, “rAAV2/2-ND4” (GS010) represents a recombinant, replication-defective, adeno-associated virus, serotype 2, containing a modified cDNA encoding the human wild-type mitochondrial ND4 protein. The rAAV2/2-ND4 construct was investigated in an open-label single-centre Phase I/II clinical trial that included 4 dose-escalation cohorts (9 × 109 vector genomes [vg]/eye, 3 × 1010 vg/eye, 9 × 1010 vg/eye, 1.8 × 1011 vg/eye) and an extension cohort (9 × 1010 vg/eye). Fifteen (15) participants with LHON that carried the ND4-G11778A mutation were recruited to the study and each subject received a single intravitreal injection of rAAV2/2-ND4 in the worse-seeing eye. The clinical trial design included a follow-up period of 48 weeks and a longer-term follow-up for an additional 4 years with a primary objective of safety and tolerability following escalating doses of rAAV2/2-ND4. Results announced to date by the company indicated that at week 96 there were no unexpected treatment emergent adverse events (TEAEs), no serious adverse events (SAEs) related to the treatment or procedure, and no suspected unexpected serious adverse reactions (SUSARs). 94% of the reported TEAEs were mild in intensity and at week 96, no related TEAEs required ongoing treatment.


In their publication, the research team, led by Dr. Catherine Vigal, investigator of the study and Chief of the Department of Ophthalmology at the Rothschild Foundation Hospital in Paris, concluded that, “[o]ur study demonstrates that rAAV2/2-ND4 is safe and well tolerated 2 years after a single unilateral intravitreal administration. Our 2 ongoing Phase III clinical studies in similar subjects, RESCUE (vision loss duration of ≤ 6 months) and REVERSE (vision loss duration of >6 months to 1 year), should help refine and inform the trends of improvement in visual outcome that we have reported and further validate the safety and tolerability of allotopic expression in mitochondrial disease.”