GS010 is an AAV2 gene therapy vector that encodes the human wild-type ND4 protein, which we are developing as a treatment of LHON caused by mutation of the ND4 gene.
The ND4 gene is normally located in the mitochondria where ND4 proteins are synthesized. GS010 allows efficient allotopic expression of the mitochondrial gene ND4 in the nucleus thanks to a proprietary Mitochondrial Targeting Sequence that shuttles the messenger RNA from the nucleus directly to the outer membrane of the mitochondria. There, the ND4 proteins are synthesized and incorporated into the mitochondria. Wild-type ND4 proteins then integrate into Complex I of the respiratory chain and rescue the deficiency.
We believe that GS010 can become the first curative treatment for LHON, thereby addressing a significant unmet medical need in this rare disease.
Trials with enrollment already closed
A Phase I/II trial, completed in France subjects with long-standing vision loss from LHON with the ND4 gene mutation, demonstrated that GS010 was well-tolerated.
Two Phase 3 trials (RESCUE and REVERSE), to evaluate the efficacy of GS010 in LHON patients with a recent onset of disease (i.e., less than one year), were completed in 2019 in Europe and the US. We reported full Week 48 results from REVERSE in June 2018 and Week 48 results from RESCUE in 2019. Results of follow-up visits up to Week 96 in both trials were reported in 2019. Patients in both trials were invited to participate in a long-term follow-up study, which will monitor safety and efficacy up to 5 years after injection.
A third Phase 3 trial, pursuant to a special protocol assessment with the FDA, is the ongoing REFLECT study, which will evaluate the efficacy and safety of bilateral intravitreal injection of GS010 for the treatment of vision loss up to 1 year. All patients have been enrolled are in their post-injection follow-up period. Topline results are expected in Q2 2021.
Finally, the company also completed a retrospective registry study REALITY to study the evolution of visual function among untreated LHON patients. This study completed patient recruitment in 2019.
Studies being initiated
There are currently no trials involving GS010 that are enrolling patients.
Expanded access / compassionate use
In some circumstances, a patient may not be able to participate in a clinical trial. Seeking use of an investigational medication under these circumstances is permitted by the FDA and commonly referred to as compassionate use or expanded access. Our policy is intended to comply with U.S. Food and Drug Administration (FDA) requirements for any such use or access. Please see the attached document for details.
Scientific publicationSafety of intravitreal gene therapy for treatment of subjects with Leber Hereditary Optic Neuropathy due to mutations in the mitochondrial ND4 gene – The REVEAL study. Vignal-Clermont C. et al. BioDrugs, Feb. 2021
Scientific publicationEfficacy and safety of intravitreal gene therapy for Leber hereditary optic neuropathy treated within 6 months of disease onset. Newman N.J. et al., Ophthalmology, Jan. 2021
Scientific publicationBilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy. Yu-Wai-Man P. et al., Sci Transl Med. Dec. 2020
Scientific publicationImmune Response and Intraocular Inflammation in Patients With Leber Hereditary Optic Neuropathy Treated With Intravitreal Injection of Recombinant Adeno-Associated Virus 2 Carrying the ND4 Gene: A Secondary Analysis of a Phase 1/2 Clinical Trial; Bouquet C. et al., JAMA Ophthalmol., April 2019
Scientific publicationSafety of rAAV2/2-ND4 Gene Therapy for Leber Hereditary Optic Neuropathy. Vignal C. et al. Ophthalmology, June 2018, Volume 125, Issue 6, Pages 945–947.