Rare Daily Staff

Nightstar Therapeutics said it has initiated a late-stage trial of its NSR-REP1, an experimental gene therapy for patients with choroideremia- a rare, progressive, degenerative, retinal disorder that leads to total blindness.

The trial is expected to enroll approximately 140 patients across 18 clinical sites in the United States, Europe, Canada and South America. Patients will be randomized into one of three study arms: 56 patients receiving a high-dose of NSR-REP1 in one-eye, 28 patients receiving a low-dose of NSR-REP1 in one-eye, and 56 patients receiving no treatment.

The primary endpoint of the trial is the proportion of patients with a specified improvement from baseline in visual acuity at 12 months post-treatment. The primary endpoint will compare patients in the high-dose treatment arm with patients in the control arm.

In data from 32 patients treated with NSR-REP1 across four open-label Phase 1/2 clinical trials, more than 90 percent of treated patients maintained or improved their visual acuity over a one-year follow-up period.

“The initiation of this first-ever phase 3 trial for the treatment of choroideremia is a major milestone for Nightstar and a tremendous step forward for patients otherwise at risk of blindness due to this devastating disease,” said Dave Fellows, chief executive officer of Nightstar. “We are very encouraged by the responses we have seen to-date following treatment with NSR-REP1.”

CHM is caused by mutations in the CHM gene, which encodes REP1, a protein that plays a key role in intracellular protein trafficking and the elimination of waste products from retinal cells. Absence of functional REP1 leads to death of the RPE cells and degeneration of the overlying retina, which contains the retinal photoreceptors required to convert light into visual signals.

NSR-REP1 is comprised of an AAV2 vector containing recombinant human complementary DNA that is designed to produce REP1 inside the eye. NSR-REP1 is administered surgically by injection into the sub-retinal space, which is between the outer layers of the retina. The introduction of a functional CHM gene into patients is intended to allow expression of REP1, and slow or stopping the progression of CHM and the decline in vision.

Nightstar believes that enhanced REP1 expression may also be able to slow or reverse the early stages of cell death in already damaged retinal cells, accounting for what it says are substantial improvements in visual acuity that have been observed in some patients after treatment with NSR-REP1.

The U.S. Food and Drug Administration and the European Medicines Agency have both granted Nightstar Orphan Drug Designation for NSR-REP1 for the treatment of CHM.

March 6, 2018
Photo: Dave Fellows, CEO of Nightstar