07.06.20

GenSight Biologics Reports Sustained Efficacy and Safety Among LHON Patients 3 Years After Lumevoq Treatment

Source: GenSight Biologics

GenSight Biologics reported that Leber Hereditary Optical Neuropathy (LHON) subjects treated with Lumevoq experienced sustained efficacy and safety 3 years after a single injection with the gene therapy. These findings come from CLIN06, the long-term follow-up study to which participants in the RESCUE and REVERSE phase 3 pivotal trials were invited.

These new data will reinforce GenSight Biologics’ submission of Lumevoq for marketing authorization in the European Union, which it intends to file in September 2020.

A total of 61 patients accepted the invitation to enroll in CLIN06 (30 from RESCUE and 31 from REVERSE), making CLIN06 one of the largest long-term follow-up studies for a rare disease treatment. The subjects were treated with Lumevoq in one eye and with sham injection in the other.

At the start of the long-term follow-up, or at 2 years post-treatment, the subjects had already experienced an average gain of +18.8 letters equivalent relative to the low point (their “nadir”**) of their visual acuity in their Lumevoq-treated eyes and +17.3 letters equivalent in their sham-treated eyes. One year later, or 3 years after the one-time injection, the bilateral benefit was maintained, with Lumevoq-treated eyes recording a mean improvement against nadir of +20.5 letters equivalent and sham-treated eyes demonstrating a mean improvement of +19.4 letters equivalent.

“CLIN06 demonstrates that the clinical improvement seen in prior Lumevoq studies is real and is maintained for 3 years post treatment,” Dr. Mark L. Moster, Neuro-Ophthalmology, Wills Eye Hospital, Professor of Neurology and Ophthalmology at Thomas Jefferson University, Philadelphia, and Principal Investigator in the RESCUE, REVERSE and CLIN06 trials, said in a company news release. “These results are far better than the natural history of LHON and provide further hope for improving the lives of our patients with this blinding disease.”

Table 1. BCVA Mean Improvement Vs. Nadir** In LUMEVOQ® Long-Term Follow-Up (CLIN06)

N = 61 subjects

Year 2 Post-Injection

Year 3 Post-Injection

LogMAR

(Std Error)

Letters Equivalent*

LogMAR

(Std Error)

Letters Equivalent*

LUMEVOQ®-treated eyes

-0.375

(0.3060)

+18.8

 

-0.410

(0.3650)

+20.5

 

Sham-treated eyes

-0.346

(0.2910)

+17.3

 

-0.387

(0.3690)

+19.4

 

Note: The CLIN06 sample consists of the RESCUE and REVERSE participants who accepted to be followed in the CLIN06 study.

Safety findings at 3-years were consistent with previous readouts, which concluded that Lumevoq is well-tolerated: no serious adverse events were recorded among Lumevoq-treated eyes, and no discontinuations occurred due to ocular events. There were no systemic serious adverse events or discontinuations related to study treatment or study procedure.

“By providing more proof of the durable and clinically meaningful efficacy of Lumevoq along with its very high level of safety, these results highlight our gene therapy’s potential to treat patients with LHON and make a significant difference to their lives,” commented Bernard Gilly, Co-founder and Chief Executive Officer of GenSight. “The data add further momentum to our plans to file for approval in Europe, which we intend to do with the utmost speed.”

The pivotal trials RESCUE and REVERSE evaluated the efficacy and safety of a single intravitreal injection of Lumevoq in patients at 0-6 months and 6-12 months, respectively, from onset of vision loss due to Leber Hereditary Optical Neuropathy (LHON) in subjects carrier of a mutated ND4 mitochondrial gene.

To date, across clinical trials and cases of compassionate use, 194 patients have been treated with Lumevoq, with many followed for at least 3 years post-injection. The dose used in Lumevoq treatment, which introduces 9×1010 vg per eye, has been shown to result in negligible biodissemination.

*Assessments of best-corrected visual acuity (BCVA) were recorded in LogMAR. The change from nadir in LogMAR was converted to “letters equivalent” improvement by multiplying the LogMAR by -50 (ref. J.T. Holladay, J Refrac Surgery, 1997;13, 388-391).

**“Nadir” is defined as the worst BCVA recorded in any of the visits in RESCUE, REVERSE and CLIN06, including the baseline visit immediately prior to the injection.

 

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