Gene Therapy Continues to be Well-Tolerated in Retinitis Pigmentosa
Encouraging efficacy signals have also been observed in treated participants.
The gene therapy GS030 (GenSight Biologics) has continued to have a favorable safety profile in patients treated for retinitis pigmentosa (RP) in the phase 1/2 PIONEER trial (NCT03326336), and a Data Safety Monitoring Board (DSMB) has recommended the highest dose tested to be used in the extension cohort.
“While the primary endpoint of the study is safety and tolerability at 1 year after gene therapy administration, we have patients that are followed much longer and have already reached 3 and even 4 years post-injection, which continue to show good tolerability and safety,” investigator Élise Boulanger-Scemama, MD, Adolphe de Rothschild Foundation Hospital, Clinical Investigation Center CHNO des 15-20, said in a statement. “Those results for GS030 are particularly encouraging and could bring back hope for patients suffering from end-stage RP with currently no therapeutic solution.”
GS030 is an investigational optogenetic treatment that combines an adeno-associated virus vector (AAV2) gene therapy (GS030-DP) with the use of light-stimulating goggles (GS030-MD) to potentially restore vision in patients with end-stage RP. The therapy delivers the gene for the light-sensitive ChrimsonR-tdT protein into retinal ganglion cells to make them responsive to light and bypass photoreceptors damaged by RP or other degenerative retinal diseases as it is a gene-independent therapy. GS030-MD use is then required to activate ChrimsonR-tdT and stimulate the treated retina. It has been granted orphan drug designation in Europe and the US is being evaluated in the multicenter, open-label, first-in-human, dose-escalation PIONEER trial for safety and tolerability.
READ MORE: IND for Gene Replacement Therapy for Inherited Retinal Dystrophy Cleared by FDA
PIONEER enrolled 3 patients each in 3 cohorts to receive a single intravitreal injection of 5e10 vg, 1.5e11 vg, or 5e11 vg of GS030-DP in their worst affected eye. The first use of GS030-MD took place 8 weeks after injection of GS030-DP under medical supervision and was well-tolerated. Participants were trained with using GS030-MD in parallel to scheduled study visits.
Participants experienced mild-to-moderate ocular adverse events (AEs) under grade 3, with most (70%) experiencing mild intraocular inflammation that resolved without sequelae after corticosteroid treatment. The longest follow-up was 4 years for 1 participant. The highest, 5e11 vg dose was selected by the DSMB as the recommended dose for the currently recruiting extension cohort.
All participants have reached 1 year of follow-up. GenSight has stated that encouraging signs of efficacy were observed, with some patients being able to count objects after barely perceiving light at baseline.
"Retinitis pigmentosa is the most frequent blinding genetic disorder for which there is currently no treatment. The safety data and early efficacy signals from our PIONEER trial are highly encouraging and suggest that our optogenetic treatment candidate could offer hope to the many patients affected," Bernard Gilly, cofounder and chief executive officer, GenSight Biologics, added to the statement. "We are looking forward to further data from the extension cohort that is under recruitment and expect then to move GS030 to efficacy trials."
