GenSight Biologics Announces Publication of Results from LUMEVOQ® RESCUE Pivotal Phase III Trial in AAO journal Ophthalmology®

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PARIS: GenSight Biologics, a biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, today announced that the journal of the American Academy of Ophthalmology, Ophthalmology®, has published results from the RESCUE pivotal Phase III clinical trial of LUMEVOQ® gene therapy in ND4 Leber Hereditary Optic Neuropathy (LHON) subjects. The paper*, published in the January issue under the title, “Efficacy and safety of intravitreal gene therapy for Leber hereditary optic neuropathy treated within 6 months of disease onset”, is the second peer-reviewed article based on Phase III clinical trial data to document comparable bilateral improvement in visual outcomes from a unilateral injection of a gene therapy. 

“The improvement from nadir in both eyes is compelling and not consistent with what we know about the natural history of this disease,” said Dr. Nancy J. Newman, MD, lead author, RESCUE principal investigator and LeoDelle Jolley Professor of Ophthalmology and Neurology at the Emory University School of Medicine in Atlanta, GA, USA.

“The study confirms the clinical benefit of rescuing retinal ganglion cells and optic nerve fibers with Mitochondrial Targeting Sequence (MTS)-based gene therapy,” said Dr. José-Alain Sahel, MD, co-founder of GenSight and Director of the Institut de la Vision (Sorbonne-Université/Inserm/CNRS), Paris, France, where LUMEVOQ®’s underlying mitochondrial targeting technology was developed. “Numerous other mitochondrial diseases could be efficiently targeted as demonstrated in this pivotal clinical trial,” added Dr. Sahel, who is also Chairman of the Department of Ophthalmology at Centre Hospitalier National d’Ophtalmologie des XV-XX, Paris, France, and Professor and Chairman of the Department of Ophthalmology at the University of Pittsburgh School of Medicine and UPMC (University of Pittsburgh Medical Center), USA.

RESCUE trial data and analyses were key components of the data package submitted by GenSight Biologics in September 2020 to the European Medicines Agency when it applied for marketing authorization for LUMEVOQ® as treatment for patients with visual loss due to LHON caused by a confirmed mutation in the ND4 mitochondrial gene. The agency’s decision is expected in Q4 2021.

Meanwhile, topline results for a third Phase III trial, REFLECT, are expected in Q2 2021.

Key RESCUE Trial outcomes

39 ND4 LHON subjects, who experienced vision loss within 6 months in at least one eye and vision loss of no longer than 6 months in both eyes at time of enrollment, participated in the RESCUE trial. As in the REVERSE trial, one eye received LUMEVOQ® gene therapy through an intravitreal injection while the other eye received a sham injection. The subjects were followed for 96 weeks after their injection; topline results at Week 96 were reported in 2019.

Efficacy analysis from 38 subjects1 show that best-corrected visual acuity (BCVA) evolved along parallel trajectories for LUMEVOQ®-treated and sham-treated eyes, deteriorating to the worst levels at Week 24, followed by a plateau phase until Week 48, then showing improvement up to Week 96. By Week 96, average change against the worst recorded BCVA, or nadir, was -0.53 LogMAR (+26 ETDRS letters equivalent) in LUMEVOQ®-treated eyes and -0.46 LogMAR (+23 ETDRS letters equivalent) in sham-treated eyes. This improvement was statistically significant in both eye groups (p<0.0001).

At Week 96, 71% of subjects had an improvement of at least -0.3 LogMAR (+15 ETDRS letters equivalent) from the nadir in at least one eye and 71% of subjects had Clinically Relevant Recovery (CRR) from nadir in at least one eye. CRR, a measure of treatment response established by an international consensus meeting on the management of LHON2, is defined as either an improvement from off-chart BCVA to on-chart, or an on-chart improvement BCVA of at least -0.2 LogMAR, or +10 ETDRS letters.

Improvement in quality of life metrics relative to baseline values taken before treatment, as assessed by the well-established National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25), was clinically relevant3 in the subscales related to mental health, dependency, and role difficulties.


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