Nanoscope preps filing for retinitis pigmentosa gene therapy

Nanoscope Therapeutics is on the brink of filing for FDA approval of what could be the first gene therapy for incurable eye disease retinitis pigmentosa (RP) that can be used regardless of underlying genetic mutations.

The Dallas, Texas-based biotech said it plans to submit a dossier to the FDA later this year after its MCO-010 (sonpiretigene isteparvovec) gene therapy achieved almost all its primary and secondary efficacy objectives in the phase 2b RESTORE trial.

Approximately 100,000 people in the US and an estimated 2 million people worldwide suffer from RP, a condition that results in progressive damage to light-detecting cells in the retina and is the leading cause of inheritable blindness.

MCO-010 consists of a gene that codes for the light-sensitive MCO protein, carried by an adeno-associated virus (AAV) vector, which is administered into the eye by intravitreal injection and is designed to restore the function of retinal cells.

In RESTORE, a once-off administration of the gene therapy led to a “clinically meaningful” improvement in legally blind RP patients who had progressive and permanent neurodegeneration of the retina, according to the company.

There was a statistically significant improvement in best-corrected visual acuity (BCVA) at week 52 in both high-dose and low-dose MCO-010 treatment groups compared to a control group that had sham injections.

The improvement in both groups was greater than 0.3 units on the LogMAR scale of visual acuity, which signifies a marked improvement in vision. That was sustained for 76 weeks in patients getting the high dose of the gene therapy, which will be submitted for FDA approval, but not in the low-dose arm.

It is the first pivotal trial of a mutation-agnostic RP gene therapy and the only study to show a 0.3 or better LogMAR improvement in retinal degenerative disease, according to Nanoscope. The study also found improvements in other visual measures, including shape discrimination and the Y mobility test, which measures how well patients are able to navigate between lit and unlit LED lights in a room, at varying levels of brightness or luminance.

At the moment, Luxturna (voretigene neparvovec) is the only approved gene therapy for RP, and is indicated only for a small subpopulation of patients with the RPE65 gene mutation, estimated to represent 1% or less of all cases of the disease. Other therapies directed at specific mutations – including Ocugen’s OCU400, Beacon Therapeutics’ AGTC-501, and Frontera Therapeutics’ FT-002 – are in clinical trials.

Thousands of mutations across more than 50 genes have been associated with RP, so a gene therapy that works across the board could have major implications for patients.

RESTORE trial investigator David Boyer of the University of Southern California Keck School of Medicine said the results were remarkable, as the researchers saw “significant vision restoration in many patients with severe vision loss, including those who were completely blind.”

He added: “If approved, MCO-010 is poised to make a positive, meaningful impact on the lives of patients affected by this debilitating condition.”

Photo by Taras Chernus on Unsplash