GenSight’s RESCUE Trial Shows Positive Results for Rare Eye Disease

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Paris-based GenSight Biologics reported the first group of data from Week 96 of its RESCUE Phase III clinical trial. The trial is studying a single intravitreal injection of GS010 in 39 patients who have lost vision because of 11778-ND4 Leber Hereditary Optic Neuropathy (LHON).

LHON is a rare mitochondrial genetic disease inherited from the mother. It is marked by the degeneration of retinal ganglion cells. This results in significant and irreversible vision loss that can lead to legal blindness. It mostly affects young adolescents and young adults. Although painless, it is typically sudden, with loss of central vision in one eye, then the second eye. It effects about 1,400 to 1,500 new patients every year in the U.S. and Europe.

RESCUE and REVERSE are two separate but parallel Phase III trials evaluating the efficacy of a single intravitreal injection of GS0101 in patients with LHON from the G11778A mutation in the mitochondrial ND4 gene. The primary endpoint is the difference in efficacy of GS010 in treated eyes compared to eyes treated with a sham (placebo) injection based on Best-Corrected Visual Acuity (BCVA), measured with the ETDRS at 48 weeks after injection.

Both trials were run simultaneously, with 37 patients in REVERSE and 39 in RESCUE, in seven sites in the U.S., UK, France, Germany and Italy.

In RESCUE, data suggests continued efficacy of the drug two years after injection, with BCVA holding clinically meaningful improvement. Patients receiving the drug had their eyesight initially get worse to a point defined as the nadir, or worst point, where it then started to recover.

Patients receiving the drug regained more than two-thirds of the initial vision loss observed at the most acute phase of the disease. These results are very similar to those seen in the REVERSE trial.

“The results from the RESCUE study are encouraging and convincing, particularly because we are seeing a similar pattern to the REVERSE study results,” said Mark L. Moster, Neuro-Ophthalmology, Wills Eye Hospital, Professor of Neurology and Ophthalmology at Thomas Jefferson University in Philadelphia, and principal investigator in both trials “Patients in RESCUE were treated before the nadir so, as expected, they continued to worsen early on. But then from week 48 until week 96 they experienced a recovery from the nadir. That is much better than the natural history in any prior studies.”

The RESCUE trial, reported in February 2019, was actually a failure, failing to meet its primary efficacy endpoint, defined as a +15-letter difference in visual acuity improvement for GS010-treated eyes compared to sham-treated eyes at 48 weeks.

At the time, Jose-Alain Sahel, Director of the Institut de la Vision (Sorbonne-Universite/Inserm/CNRS), Paris, and chairman of the Department of Ophthalmology at the University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), as well as co-founder of GenSight, said, “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.”

The company indicates, with this final readout, that is plans a pre-submission meeting with the European Medicines Agency (EMA) in early 2020 and expects to submit a marketing approval application in Europe in the third quarter of 2020. An End of Phase II meeting with the U.S. Food and Drug Administration (FDA) has been requested and is expected in November 2019.


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