LumevoqLeber hereditary optic neuropathy (LHON)
New molecular entity
Development and Regulatory status
Phase III Clinical Trials
Phase III Clinical Trials
Apr 22GenSight announces a further delay. This is due to a delay in completing the validation (PPQ) batches for Lumevoq because of the need to implement operational adjustments that will prevent recurrence of issues with the latest PPQ campaign. The Company targets the restart of the campaign in Q4 22. The latest campaign, which was initiated after the Company addressed an equipment issue that caused the 2021 campaign to fail, generated drug substance whose viral genome titer fell below the acceptance threshold. Resulting investigations led by external experts have traced the outcome to operational difficulties in specific stages of the downstream process. To prevent the repeat of these issues, the Company is working with its manufacturing partner to implement targeted corrections around enhanced process control and more rigorous supervision inside the manufacturing suites. In addition, the Company has decided to manufacture smaller engineering lots to confirm the robustness of the corrective actions. The supply of Lumevoq vials available for compassionate use has been used up, so treatments can only resume in early 2023 when test results confirm the quality of the product from the new PPQ campaign. GenSight has initiated discussion of the new manufacturing timeline with the EMA, while finalising all Day 120 responses not related to the manufacturing of the PPQ batches. The Company will provide an update as soon as the Agency has given its feedback .
Nov 21GenSight announces a 9 month delay in its EMA licence application due to a manufacturing issue (technical related to operational conditions and not to the intrinsic design of the manufacturing process). It had previously asked for a clock stop and the review was due to resume in Jan 22. As a result of the new manufacturing timeline, GenSight has requested a 9-month extension to the current D120 clock stop .
Sep 21Granted Promising Innovative Medicine (PIM) status by the MHRA .
Nov 20GenSight reports that reported that the LUMEVOQ® Marketing Authorisation Application (MAA) passed validation checks required for submissions to the EMA, triggering the official start of the MAA review procedure. GenSight plans to file in the US in H2 21 .
Sep 20Filed in the EU for patients with vision loss due to Leber Hereditary Optic Neuropathy (LHON), caused by mutation in the ND4 mitochondrial gene .
Apr 20US filing with the FDA planned for Q2 2021 
Apr 20Company reports completion of pre-submission meeting with the EMA and plans to file in September 
Dec 19Plans to file in EU in 2020 
May 19EMA filing anticipated Dec 2019 and FDA filing H2 2020 .
May 19Following report of positive 96-week data from the PIII REVERSE trial, GenSight Biologics are moving forward to regulatory approval and working to prepare the pre-submission meeting with the EMA and End of Phase 2 meeting with the FDA .
Feb 19Planned filing may be delayed following 48 week results of RESCUE trial. 
May 18GenSight Biologics plan regulatory filings in the EU and US Q2 2019, with approval by Q4 2019 and launch in 2020 
Mar 17Has orphan drug status in EU & US .
An in vivo gene therapy using an adeno-associated virus 2 (AAV2) vector to deliver normal copies of ND4 gene directly to the mitochondrial membrane of retinal ganglion cells where it restores function. Given as a single injection into each eye.
A study of North East England found that 11.8 per 100,000 had the LHON gene but the incidence of the disease was 3.22 per 100,000. The incidence of blindness due to LHON was 1 in 14,000 .
Leber hereditary optic neuropathy (LHON)
Trial or other data
Jan 22Company announce data from RESTORE (CLIN06) study showing patients continue to experience improved vision 4 years after a single treatment, with a mean improvement against nadir of +22.5 letters equivalent vs +20.5 with sham-treated eyes .
Dec 21Company announces 2-year follow-up of REFLECT PIII trial (n=98). At 2 years after injection, statistically significant visual acuity improvement from baseline and nadir in Lumevoq treated eyes, is sustained and 73% of bilaterally treated subjects experience at least +15 ETDRS letters vs. nadir .
Sep 20Pooled efficacy data from clinical trials in LHON and natural history studies released by GenSight showed a statistically significant and clinically meaningful difference between the visual outcomes in lenadogene nolparvovec-treated patients (n = 76) and untreated patients (n = 208). Treated eyes showed progressive and sustained improvement from month 12 to month 52, in contrast to the absence of recovery over the same period for untreated eyes. At month 18, the difference became statistically significant (p = 0.01). By month 48, the difference between the mean visual acuity in treated patients and that in untreated patients was both statistically significant (p < 0.01) and clinically meaningful (-0.33 LogMAR, or +16.5 ETDRS letters equivalent, in favor of treated eyes). The data included completed PIII trials RESCUE and REVERSE studies and interim results from the long-term follow-up CLIN06 study vs. matched sample data from the REALITY registry study and 10 other natural history studies. Separate analyses of patients enrolled in RESCUE and REVERSE demonstrated similarly favourable results, when compared with untreated patients .
Dec 19UK trial sites; Moorfields 
May 19Gensight report first set of data from week 96 of PIII REVERSE trial of single intravitreal injection (n=37) of GS010. GS010 showed continued efficacy 2 years after injection, with best-corrected visual acuity (BCVA) holding a clinically meaningful improvement over baseline. At Week 96, GS010-treated eyes showed a mean improvement of -0.308 LogMAR compared to baseline, equivalent to +15.4 ETDRS letters or 3 lines on the ETDRS vision chart. BCVA in sham-treated eyes evolved on a relatively parallel trajectory, achieving a mean improvement of -0.259 LogMAR over baseline, or a gain of +12.9 ETDRS letters equivalent, at Week 96. Although lower in magnitude, the mean BCVA improvement of sham-treated eyes was not statistically significant from that of GS010-treated eyes [8,9].
Feb 19REFLECT (NCT03293524), a randomised, double-masked, placebo-controlled PIII trial evaluating the safety and efficacy of bilateral injections of GS010 in pts up to one year from onset of vision loss due to LHON is ongoing. The estimated primary completion date is Jun 2020. [6,7]
Feb 19Week 96 data will be available in Q2 2019 for the REVERSE trial.
Feb 19Topline results of PIII RESCUE trial failed to show a significant effect in pts treated within 6m of visual loss onset due to LHON. At Week 48, change from baseline for eyes treated with a single intravitreal injection of GS010 (n=39) was -19 ETDRS letters equivalent vs. -20 ETDRS letters equivalent in the eye(s) treated with sham injection (i.e. +13 ETDRS letter improvement for GS010-treated eyes vs. +11 ETDRS letters in sham-treated eyes). The primary efficacy endpoint, defined as a +15-letter difference in visual acuity improvement for GS010-treated eyes vs. sham-treated eyes at 48 weeks, was therefore not met. GS010 reported to be safe and well-tolerated. The company pointed out that there were some trends pointing toward GS010 efficacy and plan to evaluate pts again at 72 and 96 weeks; results are expected in Q2-3 2019. 
Jan 18Long-term follow-up study (NCT03406104) to the REVERSE and RESCUE trials has started recruiting (n=74 planned). The goal is to assess the long-term safety and efficacy of GS010 and assess the quality of life in subjects with Leber Hereditary Optic Neuropathy due to the G11778A ND4 mitochondrial mutation. Primary outcome measures are AEs or SAEs (ocular or systemic) related to GS010 or administration procedure reported during the follow-up visits (2, 2.5, 3, 4, and 5 years) from the period of 96 weeks up to 5 years post-treatment and summarised descriptively by type, frequency (number, percentage), severity, causal relationship, and seriousness. Estimated primary completion date is Jul 2022 .
Feb 17PIII REVERSE study has completed recruitment. Collection of primary outcome data is expected to complete Jan 18, and also in the RESCUE study .
Jan 16GenSight Biologics initiates the PIII REVERSE trial to investigate safety and efficacy of GS 010 in patients affected for more than 6 months and to 12 months by LHON due to the G11778A mutation in the ND4 Gene (NCT02652780; GS-LHON-CLIN-03B). ETDRS visual acuity at Week 48 after intravitreal injection will be assessed as the primary endpoint. 36 patients will be recruited in the US, France, Germany, Italy and the UK .
Jan 16GenSight Biologics initiates the pivotal PIII RESCUE trial to evaluate efficacy of GS 010, administered as a single intravitreal injection, for treatment of vision loss in patients affected for 6 months or less by LHON due to the G11778A mutation in the mitochondrial ND4 gene (NCT02652767). ETDRS visual acuity at Week 48 after intravitreal injection will be assessed as the primary endpoint. The study is enrolling approximately 36 subjects in the US, France, Germany, Italy and the UK .