The new data builds upon positive long-term follow-up data from clinical trials.
Gensight Biologics’ lenadogene nolparvovec (Lumevoq), an investigational gene therapy intended to treat Leber hereditary optic neuropathy (LHON) caused by the m.11778G>A ND4 mutation (MT-ND4), has demonstrated improvements in best corrected visual acuity (BCVA) among patients treated in early access programs. The findings were presented at the Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting, held April 23-27, in New Orleans, Louisiana.1
Among 38 patients who received treatment with Lumevoq in 1 or both eyes and were evaluable at 1 year post-treatment, there was a mean change in BCVA from baseline to 1 year of -0.29 LogMAR (+14.5 EDTRS letters equivalent; standard deviation [SD], 0.67). Furthermore, among the 25 patients who received Lumevoq in both eyes, there was a mean change in BCVA from baseline to 1 year of -0.36 LogMAR (+18 ETDRS letters equivalent; SD, 0.73). Chiara La Morgia, an assistant professor at the Institute of Neurological Sciences of Bologna, who presented the data, and colleagues noted that the safety profile seen among patients treated in early access programs has been favorable and in line with expectations.
“Patients receiving lenadogene nolparvovec in the early access programs were predominantly European and received therapy mostly in both eyes,” La Morgia and colleagues wrote.1 “Preliminary efficacy and safety analyses show that lenadogene nolparvovec injection was associated with a clinically meaningful improvement of visual acuity and a favorable safety similar to that observed in clinical studies.”
The study includes 63 patients with MT-ND4-LHON in total who received treatment with Lumevoq in early access programs between August 2018 and March 2022. The ages of the patients at the time of first Lumevoq injection ranged from 13.5 to 74.7 years (mean, 34.5; SD, 16.6). Thirty-five (55.6%) of the patients received treatment in France, 9 (14.3%) received treatment in Italy, 18 (28.6%) received treatment in the US, and 1 patient (1.6%) was treated in the United Kingdom. The group includes 42 patients (66.7%) who were treated in both eyes. All of these patients except 1 received treatment in both eyes on the same day. A majority of the patients (72.6%) were receiving ongoing treatment with idebenone therapy when Lumevoq was administered. Among 62 patients for whom data was available, loss of vision in the first affected eye had lasted for a mean of 11.4 months (SD, 9.7) at the time of the first Lumevoq injection. The investigators noted that Lumevoq was authorized for use in the early access programs by local regulations and that the treatment was provided based on unsolicitied requests. All patients received a dose of 9x1010 viral genomes/eye.
These findings build upon positive long-term follow-up data from the phase 3 RESTORE clinical trial (NCT03406104) evaluating Lumevoq, which were also presented at the ARVO 2023 annual meeting.2 Patrick Yu Wai Man, PhD, FRCPath, FRCOphth, professor, ophthalmology, University of Cambridge, who presented the data, and colleagues found that participants in this trial, which treated patients with Lumevoq in 1 eye and sham treatment in the other eye, had a bilateral absolute mean improvement in BCVA from nadir to 2 years of +22.0 EDTRS letters in the treated eyes and +19.5 EDTRS letters in the sham-treated eyes. The investigators also noted that the safety profile was similar to that seen in earlier follow-up data.
GenSight Biologics submitted a marketing authorization application for Lumevoq to the European Medicines Agency (EMA) in September 2020.3 Although, on April 20, 2023, the company announced that it had pulled the application, citing an indication from the EMA’s Committee for Advanced Therapies (CAT) that the data submitted would not be sufficient for approval.4
“We disagree with the current CAT assessment and remain highly confident in the clinical benefit of LUMEVOQ for LHON patients, which is supported by extensive evidence from multiple clinical trials and real-world data,” Bernard Gilly, the CEO and co-founder of GenSight Biologics, said in a statement.4 “The decision to withdraw our application allows us to continue to work with EMA to agree as soon as possible on a regulatory path forward. I want to thank the patient communities for their support and reaffirm our determination to bring this innovative therapy to ND4-LHON patients in need of an efficacious treatment. I also want to thank the scientific community and our teams for their long-lasting commitment.”
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