A gene therapy mystery? GenSight blasted as 1st PhIII eye study ends in an intriguing failure

GenSight has a gene therapy mystery on its hands, which is about the last thing it wanted at the end of Phase III.

Assessing the 48-week data from its first pivotal test of a treatment for Leber Hereditary Optic Neuropathy — or LHON, a rare genetic disease that causes blindness — investigators pulled out a meaningful improvement in sight in their one treated eye.  

Bernard Gilly

The mystery: The other eyes that received a sham therapy did just as well with their eyesight. Exactly as well.

That makes the Phase III study of GS010 a failure, and rather than stay to try and solve the mystery, investors bailed, driving down the EuroNext stock $SIGHT down by 34%.

One of the reasons why the early gene therapy pioneers like GenSight picked hereditary eye diseases to go after first is that the eye is a contained unit, limiting off-target effects. But GenSight’s Paris-based CEO Bernard Gilly says that as only a fraction of patients historically see a spontaneous improvement in eyesight, he’s wondering if the therapy injected into one eye delivers an unexpected benefit to the other.

At the same time, GenSight touted a hit on a retinal biomarker for the disease, which they claimed as evidence that the therapy had an impact separate from the sham.

“The fact that structural measures of the retina showed such a large statistical difference with treatment is compelling and objective evidence that this gene therapy protects the integrity of many retinal ganglion cells from the damage of LHON,” commented company co-founder José-Alain Sahel.

That’s a messy argument, with the company arguing that it appeared the therapy improved sight for both eyes, but only hit the secondary biomarker in the treated eye. 

The company — which tried and failed to make it onto Nasdaq — will be left looking for more data to analyze from its next two Phase III studies, which are upcoming. But easy explanations will be hard to come by.