Top-line data from the recently completed phase 2b RESTORE trial of MCO-010, an investigational gene therapy being developed by Nanoscope Therapeutics for patients with advanced retinitis pigmentosa (RP), show clinically meaningful vision improvement in legally blind individuals with progressive and permanent neurodegeneration of the retina, the company recently reported.
RESTORE was a multicenter, randomized, double-masked, sham-controlled, dose-ranging study to evaluate 2 dose levels of MCO-010 in patients with advanced RP, based on clinical examination, dilated fundus examination, and genetic testing. Nine subjects received a single intravitreal injection containing a high dose (1.211 genomic copies [gc]/eye) of MCO-010, 9 received an injection with a low dose (0.911 gc/eye) of MCO-010, and 9 received a sham injection. All subjects were assessed for 100 weeks following treatment.
The trial met its primary endpoint of statistically significant best-corrected visual acuity (BCVA) improvement at week 52 in both the high-dose (0.337 LogMAR; P=.021) and low-dose (0.382 LogMAR; P=.029) treatment groups compared to the sham control group (0.050 LogMAR). Improvements in visual function persisted or increased following week 52 in the study, demonstrating the durable effect of MCO-010. BCVA improvement at week 76, a key secondary endpoint, was statistically significant in the high-dose treatment group compared to the control group (0.539 LogMAR; P=.001). At week 76, the improvement in BCVA in the low-dose treatment group was not statistically significant compared to control (0.374 LogMAR; P=.065). These results are consistent with what has been previously observed in the earlier phase 1/2a open-label study.
“We observed significant vision restoration in many patients with severe vision loss, including those who were completely blind,” David Boyer, MD, an investigator in the trial and adjunct clinical professor of ophthalmology at the University of Southern California Keck School of Medicine, said in a news release. “Many patients treated with MCO-010 derived a clinically meaningful benefit measurable on the primary visual function test, and this effect was confirmed by a parallel improvement in functional vision assessments."
RESTORE was the first randomized, controlled trial of a mutation-agnostic gene therapy for a genetic disease, according to the company. In a news release, Nanoscope Therapeutics said RESTORE is the only randomized controlled trial in retinal degenerative disease to demonstrate improvement beyond the clinically important BCVA >0.3 LogMAR threshold in a statistically significant manner.
MCO-010 has received both orphan drug and fast track designations from the FDA. Nanoscope expects to submit a biologics license application (BLA) to the US Food and Drug Administration (FDA) in the second half of 2024. According to the company, the high-dose MCO-010 (1.211 gc/eye) is planned to be the commercial dose.
