GenSight’s second LHON gene therapy PhIII stumbles out of the gate — just like the first time

However GenSight’s gene therapy for Leber hereditary optic neuropathy works, it clearly has no significant effect at 48 weeks. But that doesn’t mean the biotech has lost hope in their drug.

The Paris-based biotech reported early Monday that GS010 flopped in their Phase III confirmatory trial at 48 weeks, falling far short of the mark researchers set for an improvement in the sight of the treated eye compared to the sham therapy offered in the other eye. Vision in both eyes deteriorated at almost exactly the same rate.

Bernard Gilly

Researchers also saw a matchup between the therapy and a placebo in the first Phase III, but the company went on to establish a successful readout for their 72-week data in the first REVERSE study — and that’s what they’ll be anxiously hoping to see in this study. Another evaluation at 96-weeks will be used to cap the study with close to 2 years of monitoring time.

The latest 48-week data also highlighted two other key failures: change from baseline of temporal retinal nerve fiber layer missed statistical significance as well as papillo-macular bundle thickness and ganglion cell volume. But the investigators spotlighted other trends that they say were positive indicators — not unusual for a failed readout.

GenSight may have been ready with an explanation, but not all investors were content to see the second trial get started with another setback at 48 weeks. The biotech’s stock {$SIGHT on the Paris exchange) tumbled 19%.

It’s just a matter of time for the therapy to start working, the biotech cautioned. And they’ll continue to push regulators for a quick approval of the gene therapy for a rare mitochondrial disease that destroys vision.

José-Alain Sahel

“The powerful and rapid degeneration of neurons early in the disease, combined with the time needed for GS010 to cause functioning proteins to be expressed, may be confounding efficacy measurements early in the active progression phase,” noted the Sorbonne’s José-Alain Sahel, director of the Institut de la Vision.

“As expected, the RESCUE results at Week 48 present a more complex picture because of the intense, brutal and extremely rapid onset of the retinal ganglion cells’ degeneration.” said Bernard Gilly, co-founder and CEO of GenSight. “But as with REVERSE, later readouts are likely to confirm our confidence in the efficacy of GS010.”

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Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT
Director of Operations
Atlas Venture Cambridge, MA

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