US researchers investigating an optogenetic therapy with “the potential to address all retinitis pigmentosa (RP) genetic variations” reported significant efficacy in a phase 2b/3 trial. 

Nanoscope Therapeutics’ multi-characteristic opsin (MCO-010) is delivered via an adeno-associated virus in a single-dose intravitreal injection. It targets retinal bipolar cells (that don’t normally sense light but often survive after photoreceptors die), delivering the MCO gene and effectively turning them into new photoreceptors. 

The two-year Restore study’s 27 subjects were randomised to receive low-dose MCO-010, high-dose MCO-010 or sham injection. At week 52, 40% of MCO-010 patients had improvements in BCVA (best corrected visual acuity) greater than 0.3 units on the LogMAR scale, corresponding to three lines of 15 Early Treatment Diabetic Retinopathy Study letters. That rose to 56% of patients by week 76, with continued gains noted by researchers exclusively in the high-dose group. 

Announcing these data at the 2024 Annual Meeting of the American Academy of Ophthalmology (AAO), Professor Allen Ho, Sidney Kimmel Medical College of Thomas Jefferson University, said the statistical significance achieved at multiple time points during the study is highly noteworthy. “This degree of improvement has never before been observed in a randomised, controlled trial of a highly heterogenous patient population treated with this mutation-agnostic gene therapy.”  

Although not all patients responded to intervention, 40–50% gaining three lines of vision was surprisingly strong, he said. “For example, some study subjects improved from baseline light perception vision to 20/400 or even better.” 

The FDA has already granted MCO-010 Fast Track designation, and Nanoscope Therapeutics said it expects to initiate a Biologics License Application submission in early 2025.