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GenSight Biologics proclaims the publication of outcomes from the pivotal LUMEVOQ® REFLECT medical examine in peer-reviewed scientific journals

  • Efficacy and safety results published 1.5 years after treatment in the Journal of Neurology BRAIN.

  • Publication of population characteristics ND4-LHON of the study before treatment in the diary BMJ1 Open ophthalmology.

PARIS–(BUSINESS WIRE)–Regulatory News:


GenSight Biologics (Euronext: SIGHT, ISIN: FR0013183985, PEA-PME eligible), a biopharmaceutical company dedicated to the development and commercialization of innovative gene therapies for neurodegenerative diseases of the retina and central nervous system, announced today that the renowned journal for neurology BRAIN published efficacy and safety results 1.5 years after treating patients ND4-LHON treated with lenadogenic nolparvovec (LUMEVOQ®) in the pivotal REFLECT clinical trial.

The results of REFLECT, including the top line was announced by the company on June 30, 2021, show a statistically significant improvement in visual acuity in patients ND4-LHON compared to baseline in eyes treated with LUMEVOQ®, with an additional effect for patients who received bilateral injection compared to unilateral treatment (Figure 1). A good safety profile was observed and was comparable in unilaterally and bilaterally treated patients, demonstrating the positive contribution of bilateral injections of LUMEVOQ®.

These results demonstrate that LUMEVOQ significantly improves visual acuity in patients with LHON, with likely additional benefit when patients are treated bilaterally. “, said Patrick Yu-Wai-Man2MD, PhD, Professor of Ophthalmology and Honorary Advisor in Neuro-Ophthalmology at the University of Cambridge, Moorfield’s Eye Hospital, at the UCL Institute of Ophthalmology, UK, and Principal Investigator of REFLECT. ” They also show that this effectiveness is achieved with a good safety profile. This gene therapy offers real hope for patients affected by this devastating blinding disease. »

REFLECT is the third phase III clinical trial evaluating the efficacy and safety of lenadogenic nolparvovec in patients with ND4-LHON. This is also the first clinical study evaluating the efficacy of a bilateral intravitreal injection (IVT) of LUMEVOQ®while in the three previous studies REVEAL1TURNING BACK2,3,4 and RESCUE3,4,5the drug was administered exclusively as a unilateral IVT. With the completion of REFLECT, LUMEVOQ® was administered to 189 patients in four clinical studies.

The article titled “Randomized study of bilateral injection of lenadogenic nolparvovec in m.11778G>AMT-ND4 liver hereditary optic neuropathy‘, is available in print and online via this link.

Additionally, BMJ Open Ophthalmologyan international peer-reviewed journal, published an analysis of patient characteristics ND4-LHON before treatment for the REFLECT study. The article titled “Study design and baseline characteristics for the REFLECT gene therapy study with m.11778G>A/ND4-LHON‘ is available online at this link.

Pre-treatment analyzes of the REFLECT population show demographics, visual function, and retinal anatomical measurements consistent with the natural history of the disease ND4-LHON6.

The patient profile of the REFLECT study, considered in conjunction with those of the REVERSE and RESCUE studies, provides important insights into the putative natural history of ND4-LHON that should guide future research on individuals carrying the mutation wear m.11778G>A “, said Prem SubramanianMD, PhD, Professor of Ophthalmology, Neurology and Neurosurgery, Sue Anschutz-Rodgers Eye Center at the University of Colorado and principal investigator of the REFLECT study.

references

1 Vignal-Clermont C, Girmens JF, Audo I, et al. Safety of intravitreal gene therapy for the treatment of patients with hereditary Leber’s optic neuropathy due to mutations in the mitochondrial ND4 gene: the REVEAL study. biodrugs. 2021;35(2):201-214.

2 Yu-Wai-Man P, Newman NJ, Carelli V, et al. Bilateral vision improvement with unilateral gene therapy injection in Leber’s hereditary optic neuropathy. Scientific Transl. medication. 2020;12(573):eaaz7423.

3 Moster ML, Sergott RC, Newman NJ, et al. Cross-sectional analysis of baseline visual parameters in subjects recruited into the RESCUE and REVERSE ND4-LHON gene therapy studies. J Neuroophthalmol. 2021;41(3):298-308.

4 Newman NJ, Yu-Wai-Man P, Carelli V, et al. Intravitreal gene therapy vs. natural history in patients with hereditary Leber’s optic neuropathy carrying the m.11778G>A ND4 mutation: systematic review and indirect comparison. front neurol. 2021;12:662838.

5 Newman NJ, Yu-Wai-Man P, Carelli V, et al. Efficacy and safety of intravitreal gene therapy in Leber’s hereditary optic neuropathy treated within 6 months of disease onset. ophthalmology. 2021;128(5):649-660.

6 Newman NJ, Carelli V, Taiel M, Yu-Wai-Man P. Visual outcomes in patients with hereditary hepatic optic neuropathy with the m.11778G>A (MTND4) mitochondrial DNA mutation. J Neuro-Ophthalmol From J North Am Neuro-Ophthalmol Soc. 2020;40(4):547-557.

About GenSight Biologics

GenSight Biologics SA (GenSight Biologics) is a biopharmaceutical company dedicated to the development and commercialization of innovative gene therapies for the treatment of neurodegenerative diseases of the retina and central nervous system. GenSight Biologics’ research portfolio is supported by two technology platforms: mitochondrial targeting (Mitochondrial targeting sequence, or MTS) and optogenetics aimed at preserving or restoring vision in patients with neurodegenerative diseases of the retina. Using its gene therapy approach, GenSight Biologics’ drug candidates are expected to provide patients with long-lasting functional visual recovery after a single intravitreal injection in each eye. LUMEVOQ, GenSight Biologics’ lead product candidate, was developed for the treatment of Leber’s hereditary optic neuropathy (LHON).® (GS010; lenadogen nolparvovec), is currently being reviewed for approval in Europe and is in Phase III prior to filing for marketing authorization in the United States (Biologics Marketing Authorization Application [BLA]). LUMEVOQ® (GS010; lenadogen nolparvovec), has not been registered in any country to date; a marketing authorization application for the treatment of hereditary optic neuropathy of Leber (LHON) is currently under review by the EMA.

About LUMEVOQ® (GS010; lenadogenic nolparvovec)

LUMEVOQ® (GS010; lenadogene nolparvovec) targets Leber’s hereditary optic neuropathy (LHON) and is based on a proprietary mitochondrial targeting sequence (MTS) technology derived from the work ofvision institute in Paris, which, when associated with the gene of interest, makes it possible to target it inside the mitochondria thanks to an AAV (Adeno-Associated Virus) vector. The gene of interest is thus transferred into the cell to be expressed there and produce the functional protein that, thanks to the specific nucleotide sequences, is transported into the mitochondria to restore the defective or absent mitochondrial function. “LUMEVOQ” was approved by the European Medicines Agency (EMA) in October 2018 as a trade name for GS010 (lenadogen nolparvovec). LUMEVOQ® (GS010; lenadogen nolparvovec), has not been registered in any country to date; a marketing authorization application for the treatment of hereditary optic neuropathy of Leber (LHON) is currently under review by the EMA.

About REFLECT

REFLECT is a multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of LUMVOQ bilateral injections® (GS010; lenadogen nolparvovec) in patients with LHON due to the NADH dehydrogenase 4 mutation (ND4).

The study included 98 subjects who started losing their sight less than a year ago and is being conducted at multiple centers in Europe, the United States and Taiwan.

In the active arm LUMVOQ® was administered as a single intravitreal injection in both eyes of each subject. In the placebo arm LUMVOQ® was administered as a single intravitreal injection in the first affected eye, while the other eye received a placebo injection.

The primary endpoint of the REFLECT study is best corrected visual acuity (BCVA) measured in LogMAR 1.5 years after treatment of the affected/unaffected second eye. The change from the baseline in second affected/unaffected eyes receiving LUMVOQ® and placebo is the primary endpoint. Secondary efficacy endpoints include: BCVA measured in LogMAR 2 years post-treatment in the second affected/unaffected eye compared to placebo and the first affected eye receiving LUMVOQ®, OCT, contrast sensitivity and quality of life scales. The first patient was treated in March 2018, the last in July 2019.

ClinicalTrials.gov identifiers:

REFLECTION: NCT03293524

_______________________

1 British Medical Journal

2 Patrick Yu-Wai-Man:

  • Cambridge Center for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

  • Cambridge Eye Unit, Addenbrooke’s Hospital, Cambridge University Hospitals, Cambridge, UK.

  • Moorfields Eye Hospital, London, UK

  • UCL Department of Ophthalmology, University College London, London, UK

contacts

GenSight Biologics
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Caillet Clothilde

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