GS010 Proves to be Safe and Tolerable During Phase I/II Trials in LHON Patients

Kaitlynn Ely

GenSight Biologics has published successful results in the Journal of the American Academy of Ophthalmology from their Phase I/II clinical trial and long-term follow-up of GS010, a therapy used to treat patients with Leber Hereditary Optic Neuropathy (LHON).

LHON is a degenerative condition in which patients experience bilateral, painless, and sudden vision loss. The disease develops in patients between 20 and 30 years of age and is more common in males. While women can carry the gene that causes LHON without developing the condition, the mutation will be passed on to their children.

Vision failure is the main symptom of LHON. Patients with a family history of the hereditary condition can also have tremors and cardiac defects, such as arrhythmias. Patients who show signs of developing LHON are unable to perform tasks like reading or driving, have blurry vision, have no sense of visual acuity, and develop optic atrophy.

In the United States, approximately 1,400 to 1,500 patients lose their sight because of LHON.

“This first-ever scientific publication of clinical data with GS010 is a major step forward for patients afflicted with LHON – a blinding disease affecting those in the prime of their life,” commented Dr. Catherine Vignal, investigator of the study and Chief of the Department of Ophthalmology at the Rothschild Foundation Hospital in Paris in a press release. “If these promising results are confirmed in the ongoing Phase III studies, GS010 would offer a meaningful and life changing therapy for those so afflicted and become the standard of care for LHON.”

GS010 uses a mitochondrial targeting sequence technology platform that addresses the defects inside the mitochondria of mutated cells using an Adeno-Associated Virus (AAV) vector.
Scientists believe this will affect the nucleotide sequencing of DNA and restore deficient mitochondrial function in affected cells.

The Phase I/II clinical trial was an open-label study that included 4 dose-escalation cohorts and an extension cohort. 15 patients with the LHON mutation were administered a single intravitral injection of rAAV2/2-ND4 in the worse-seeing eye. A follow-up appointment for each patient was conducted 48 weeks after the injection, and then another after 4 years.

Researchers analyzed the safety and tolerability of the escalating doses, the bio-dissemination and immunogenicity of rAVV2/2-ND4, and the state of visual functions in patients.
GS010 proved to be safe and well-tolerated 2 years after a single unilateral intravitreal administration. There were no unexpected serious adverse events, reactions or TEAEs related to the treatment. The most commonly reported TEAEs included intraocular inflammation and intraocular pressure elevation, with 94% of all TEAEs categorized as mild in intensity.

GenSight will begin two Phase III clinical studies, titled RESCUE and REVERSE, to evaluate the efficacy of GS010 in patients with LHON. Results will be available for the first study in April 2018 and the second study during the third quarter of 2018.

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