ATSN-101, a gene therapy for patients with Leber congenital amaurosis (LCA) caused by biallelic mutations in GUCY2D, produced an average 100-fold vision improvement among 15 trial participants, with two high-dose patients experiencing a 10,000-fold improvement, said researchers. 

That 10,000-fold improvement is the same as a patient being able to see their surroundings on a moonlit night outdoors, but who would have required bright indoor lighting before treatment, said lead author Dr Artur Cideciyan, Perelman School of Medicine at the University of Pennsylvania. “One patient reported for the first time being able to navigate at midnight outdoors, only with the light of a bonfire.” 

Writing in The Lancet, Dr Cideciyan’s team said, on average, the best covered visual acuity (BCVA) of those treated with the high dose of ATSN-101 improved by approximately –0·16 logMAR (eight letters on the ETDRS chart) 12 months after treatment. “Although a change in BCVA of 0·3 logMAR (three lines or 15 letters on the ETDRS chart) has previously been considered clinically meaningful, this level of improvement is aligned with that observed in the phase 3 trial of voretigene neparvovec (Luxturna),” they said.  

“ATSN-101 has the potential to be a first-in-class treatment for LCA1, a blinding condition with no approved treatment. The favourable safety profile and improvements in retinal sensitivity observed in this phase 1/2 clinical trial are supportive of a future randomised, controlled phase 3 trial to further investigate the efficacy and safety of this novel subretinal gene therapy,” they concluded. 

In related news, the UK’s Beacon Therapeutics announced it has received $170m (NZ$273m) funding to develop AGTC-501 (laruparetigene zovaparvovec), its gene therapy currently in a phase 2/3 clinical trial for the treatment of X-linked retinitis pigmentosa. In February 2024, the company reported interim data from the phase 2 Skyline trial showed 63% of eyes treated with high-dose AGTC-501 experienced retinal sensitivity improvement of at least seven decibels in at least five loci after 12 months.