Groundbreaking Trial for Leber’s Congenital Amaurosis

The first randomized controlled phase 3 trial of gene replacement for any human disease has succeeded at restoring functional vision in children with Leber’s congenital amaurosis (LCA), said Albert M. Maguire, MD, at Retina Subspecialty Day on Saturday.

The 20 patients treated in the study received subretinal injections of a recombinant adeno-associated virus, SPK-RPE65. The modified virus carries a gene for producing the protein that, when missing, leads to the night blindness characteristic of LCA.

One year after treatment, 65% of the treated group could navigate easily through a testing course, despite an ambient light level of 1 lux, said Dr. Maguire, principal investigator. Overall, their mean score on the validated mobility test improved by 1.9 (SD 1.0), compared with a change of 0.2 (SD 1.1) in control patients (p = .004). These effects have endured for a long as 3 years.

On full-field light threshold sensitivity testing (FST), averaged over both eyes, the treated patients (ages 4-44) experienced a 100-fold increase in light sensitivity compared with the controls (n = 9; p = .001).

There also were differences between the groups on a secondary endpoint, logMAR visual acuity, but these were not statistically significant.

Although there have been phase 3 gene therapy trials for other diseases, this is the first in which strict controls and randomization gave the outcomes high levels of statistical significance, Dr. Maguire said in an interview. “In the history of the field of gene therapy, this is definitely significant. It is the first randomized controlled phase 3 trial for a genetic disease of any kind—eye disease or otherwise,” he said.—Linda Roach

Financial disclosures. Dr. Maguire—Novartis Pharmaceuticals: C.

Disclosure key. C = Consultant/Advisor; E = Employee; L = Speakers bureau; O = Equity owner; P = Patents/Royalty; S = Grant support.