GenSight rebuilds its case for LHON gene therapy, eyeing filing next year

GenSight Biologics has reported new data from its phase 3 program for GS010, its gene therapy for an ultrarare eye disease, sparking another uptick in its share price.

The French biotech says the latest results from its REVERSE trial of GS010 (rAAV2-ND4) in Leber hereditary optic neuropathy (LHON) show quality-of-life benefits in patients treated with the one-shot therapy after 72 weeks, continuing a run of positive readouts after a setback in April that have seen its shares more than triple in the last three months.

LHON is a mitochondrial disease that can cause the optic nerve to atrophy, leading to sudden, severe loss of central vision, and has no approved therapies in the U.S., where there are an estimated 7,000 cases. In Europe, Santhera’s oral drug Raxone (idebenone) has been licensed to treat the disorder since 2015.

The REVERSE study is testing a single injection of GS0101 into the eye of 37 patients with LHON and showed in October that it was able to achieve a “clinically meaningful improvement” in visual acuity. The latest readout reveals that patients themselves are reporting improved quality of life when it comes to being able to carry out daily activities affected by vision loss, as well as other well-being measures like ocular pain and vision-related mental health.

“This tells us that clinical measurements obtained by our investigators add up to patients feeling that they can function better in day-to-day activities,” said GenSight CEO Bernard Gilly in a release. That backs up the earlier data on visual acuity and the protection of retinal ganglion cells from degeneration, he adds.

It also adds to the confidence building behind the program after the April readout from REVERSE missed its primary endpoint. The results of a second phase 3 trial—called RESCUE—are due in January and if positive will put GenSight on course for its planned filing for GS010 in Europe later in 2019 and in the U.S. the following year.

There has been speculation that Novartis—which is already a GenSight backer—may be interested in licensing the GS010 program, given its strong position in ophthalmic medicine and its decision earlier this year to acquire commercial rights to Spark Therapeutics’ Luxturna (voretigene neparvovec). Luxturna was the first FDA-approved gene therapy and is also used to treat an eye disorder, namely inherited retinal dystrophy caused by confirmed biallelic RPE65 mutations. Thus far, Novartis hasn’t made any noises about any interest.

GenSight seems to have a clear lead over its rivals in LHON gene therapy, although another candidate (scAAV2-P1ND4v2) is being tested in a clinical trial run by the University of Miami and the National Eye Institute. Spark also has an LHON program on the go, but that is still in preclinical testing.