Enrollment Complete for Trial of Therapy for Leber’s Hereditary Optic Neuropathy

GenSight Biologics has completed enrolling patients in its Phase 3 REVERSE clinical trial evaluating GS010 as a treatment for Leber’s Hereditary Optic Neuropathy (LHON).

LHON is a rare inherited mitochondrial disease that is passed on by the mother. It causes degeneration of retinal cells in an offspring, leading to irreversible loss of vision and sometimes blindness. The disease, which is caused by a gene mutation in mitochondria, usually shows up in the teens or early twenties, although it can also appear in early childhood or late adulthood.

GS010 is a proprietary technology based on a mitochondrial targeting sequence, or MTS. GS010 uses an adeno-associated virus (AAV) to deliver a non-mutant gene to the mitochondria that can override the mutation.

When the non-mutant gene reaches the inside of the cell, it produces a protein that restores mitochondrial function. Mitochondria are components of cells that convert food to energy.

REVERSE (NCT02652780) and RESCUE (NCT02652767) are Phase 3 trials. They are designed to evaluate the effectiveness of a single intravitreal injection of GS010 in people with LHON who have a G11778A mutation of their mitochondrial ND4 gene.

The pivotal trials, both randomized, double-masked, and sham-controlled, were conducted in seven centers across the United States and Europe. A sham intervention involves mimicking a therapy application — such as sticking a needle in a patient to feign injection — without administering the treatment.

REVERSE enrolled 36 patients whose vision began deteriorating at seven to 12 months. Forty-eight-week treatment results are expected by the end of the first quarter of 2018.

RESCUE is recruiting 36 patients whose vision began deteriorating in fewer than six months. Enrollment is expected to be completed by the end of the first half of 2017.

“This is an exciting time for patients and physicians, who are waiting for a safe and efficient treatment for LHON. We are encouraged by the safety and pharmacodynamics results seen in the Phase I/II study, and are now only a year away from a potential transformative treatment for LHON, should the results be positive,” Nancy J. Newman, MD, the investigator of the study, said in a press release. She is director of neuro-ophthalmology at Emory University.

GS010 has been granted orphan drug designation by the U.S. Food and Drug Administration (FDA) in the United States and by the European Medicines Agency (EMA) in the European Union. The designation provides financial and other incentives to companies to develop treatments for rare diseases.