REVERSE Phase III Clinical Trial of GS010 Shows Efficacy in LHON Patients


REVERSE Phase III clinical trial shows efficacy and safety of GS010 in patients with LHON.

This afternoon, GenSight Biologics released topline results regarding the REVERSE Phase III clinical trial, which evaluated the safety and efficacy of GS010 in patients with Leber’s hereditary optic neuropathy (LHON).

LHON is the most common primary mitochondrial DNA disorder and is characterized by painless vision loss that sequentially affects both eyes in a matter of weeks or months. It often leads to severe visual impairment or blindness.

GS010 leverages a mitochondrial targeting sequence (MTS) proprietary technology platform, which allows the platform to specifically address defects inside the mitochondria using an AAV vector (adeno-associated virus) when linked with the gene of interest. The gene is then transported into the cell for expression and production of the functional protein before being shuttled through specific nucleotidic sequences to the mitochondria in order to restore the missing or deficient mitochondrial function.

Dr Robert C. Sergott, Director, Wills Eye Hospital, Neuro-Ophthalmology and Director, William H. Annesley, Jr, EyeBrain Center, Thomas Jefferson University, Philadelphia, PA, shared his excitement regarding the news. "Preliminary optical coherence tomography [OCT] results from the REVERSE trial indicate that the biological targets of the mitochondrial DNA gene therapy have been successfully engaged in the treated eye compared to the untreated eye. The bottom line: we have excellent news for LHON patients and their families about their vision, which is remarkable for a previously untreatable disease.”1

While data is still being collected from the study’s participants for another 4 years, current results give reason to hope. The study was designed to measure the safety and efficacy of GS010. Among the data collected, the primary endpoint included the effects of GS010 measured with high resolution Spectral-Domain Optical Coherence Tomography (SD-OCT). The secondary endpoint included the change in retinal ganglion cell macular volume.

All 37 of the study participants were administered a single intravitreal injection of GS010. Those who had visual loss that was due to 11778-ND4 LHON and began between 6 and 12 months prior to the study’s treatment were allowed to participate. The favorable safety and tolerability profile of GS010 show a clinically meaningful improvement— +11 ETDRS letters (-0.218 LogMAR)—in treated eyes at 48 weeks as compared to the baseline in all 37 patients. Because untreated contralateral eyes showed a similar improvement of +11 ETDRS letters (-0.211 LogMAR), the trial did not meet its primary endpoint.

The visual acuity improvement of sham-treated eyes was unexpected (based on the natural history LHON), however; only a reported 8% to 22% of patients with the G11778 ND4 mutation experienced a partial spontaneous recovery.

Two additional ongoing Phase III trials, RESCUE and REFLECT, are currently further investigating GS010.

For more data from studies pertaining to the rare disease community, follow Rare Disease Report on Facebook and Twitter.


  1. “GenSight Biologics announces topline results from REVERSE Phase III clinical trial of GS010 in patients with Leber Hereditary Optic Neuropathy (LHON).” Business Wire. 3, Apr. 2018

Recent Videos
Signs and Symptoms of Connective Tissue Disease
How Gene and Cell Therapy Is Developing in Dermatology
Joyce Teng, MD, PhD, discusses how therapeutic advances in fields like epidermolysis bullosa should progress treatment discourse in other rare dermatoses.
The Prospect of Pz-cel in RDEB Treatment, with Peter Marinkovich, MD
Comparing New Therapies for Dystrophic Epidermolysis Bullosa
Reviewing 2023 with FDA Commissioner Robert M. Califf, MD
Dunia Hatabah, MD | Image Credit: HCPLive
Ricky Safer: What Clinicians Need to Know About PSC
Ryan T. Fischer, MD: Long-Term Odevixibat Benefit for Alagille Syndrome
Saeed Mohammad, MD: IBAT Inhibitors for Cholestatic Disease
© 2024 MJH Life Sciences

All rights reserved.