BioPharma

GenSight eyes long-term followup as second gene therapy vision loss trial misses target

The French biotech's shares were down more than 20 percent despite hopes that, as with its last Phase III trial, longer-term data would demonstrate the therapy's efficacy in LHON.

A French biotech company is hoping that longer-term follow-up data will vindicate its gene therapy for a disease that causes vision loss following its second failed Phase III study.

Paris-based GenSight said Monday that the Phase III RESCUE study of GS010 in Leber hereditary optic neuropathy, or LHON, did not meet its primary endpoint. The endpoint was for patients to show a 15-letter improvement on the ETDRS visual acuity test compared to baseline. However, patients whose eyes were treated with the therapy showed only a 13-letter improvement, whereas when their eyes were given a sham treatment, there was an 11-letter improvement. Each patient received the gene therapy via injection in one eye and sham injection in the other.

The company is now pinning its hopes on longer-term follow-up data that it hopes will show the therapy’s efficacy. “The planned readouts of RESCUE data at Weeks 72 and 96 should confirm GS010’s efficacy,” GenSight Chief Medical Officer Barrett Katz said in a statement, based on a long-term followup from its previous Phase III study.

However, investors were not impressed. The company’s shares opened down 21.3 percent on the Euronext Paris stock exchange following the news Monday, falling from 2.82 euros per share at Friday’s closing to 2.22.

Still, an initial failure, followed by longer-term data that indicated efficacy better than previously thought, would be consistent with the company’s previous Phase III trial of the therapy, titled REVERSE. In the case of that study, whose initial results were reported last April, the primary endpoint was not met because both eyes – the one treated with GS010 and the one that received the sham treatment – showed an improvement in visual acuity of 11 letters. But in 72-week followup data announced in October, the data showed that treated eyes had an increase in visual acuity of 15 letters, compared with 12 letters for sham-treated eyes.

One difference between REVERSE and RESCUE is that RESCUE enrolled patients whose vision loss due to LHON occurred up to six months before they started treatment, whereas REVERSE patients’ vision loss occurred six to 12 months prior to treatment. In LHON, vision usually reaches a nadir in three to five months before stabilizing, though the duration of that progression to nadir varies between patients. In RESCUE, mean best-corrected visual acuity for GS010-treated eyes and sham-treated eyes evolved with similar trajectories, worsening to a low point before improving at week 48.

Another Phase III study, REFLECT, dosed its first patient in March. That trial will evaluate bilateral injections of GS010 in patients up to one year from onset of vision loss. GS010 is an adeno-associated viral vector-based gene therapy. LHON is a maternally inherited disease that causes irreversible vision loss and can lead to legal blindness.

Photo: erhui1979, Getty Images

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