ReVision's Fenretinide (RT-101) Reduced Incidence of Choroidal Neovascularization by More Than 50 Percent in Patients With Geographic Atrophy in a Phase 2b Trial

SAN DIEGO, Sept. 1 /PRNewswire/ -- ReVision Therapeutics Inc. today announced that data from a Phase 2b trial show that fenretinide (RT-101) reduced the incidence of choroidal neovascularization (CNV, wet age related macular degeneration) by about 50 percent in patients with geographic atrophy (GA), the most advanced form of dry age related macular degeneration (AMD).

The data, presented Monday by Alexander M. Eaton, M.D., at the Annual Meeting of the American Society of Retinal Specialists, also showed a trend for reduced GA lesion growth rates in patients receiving fenretinide. These data suggest that fenretinide may have an effect on both GA lesion size as well as the conversion to the more sight-threatening wet form of AMD. Fenretinide is the first oral therapeutic to complete a Phase 2 trial in GA patients.

"These results are very exciting as there are currently no drug therapies for geographic atrophy, and there are no treatments for the prevention of CNV," said Dr. Eaton, who was an investigator in the trial. "We are hopeful that the complete analysis will further validate these findings as fenretinide could slow vision loss in the millions of Americans who face blindness because of this disease."

The double-masked, placebo-controlled, multicenter, Phase 2b study evaluated 246 patients with GA. Patients were randomized into three cohorts and received once-daily doses of 100 mg or 300 mg of fenretinide or placebo for 24 months. Retinal lesion size was measured by color fundus photography, fundus autofluorescence and fluorescein angiography. Patients were also evaluated by contrast sensitivity, reading rate, visual acuity, optical coherence tomography, and the incidence of CNV.

Fenretinide was well tolerated with no severe drug-related adverse events and no significant effects on normal vision function.

At the conclusion of the two-year study, 15 of 82 patients (18.3 percent) in the placebo arm progressed to CNV, while 15 of 164 patients (9.2 percent) receiving fenretinide at either dose developed CNV. While the results were statistically significant (p=0.039), this was the result of exploratory and ad hoc analyses.

Preclinical studies show that fenretinide reduces the expression of vascular endothelial growth factor (VEGF) isoforms. These proteins are known to cause aberrant growth of leaky vessels within the retina and have been implicated in severe vision loss in patients with CNV. Fenretinide was also found to upregulate the expression of complement factor H, a potent inhibitor of the inflammatory pathway. Dysfunction or deficits in complement factor H are known to significantly increase risk for development of CNV. This preclinical data suggests that the anti-angiogenic and anti-inflammatory properties of fenretinide may underlie the reduced incidence of CNV observed in the clinical trial.

The accumulation of retinol (vitamin A)-derived toxins in the eye is believed to be a significant risk factor for the development of GA. The ability of fenretinide to reduce the delivery of retinol to the eye, and therefore reduce accumulation of these toxins, is thought to mitigate this risk. Analysis of GA lesion growth by color fundus photography showed a trend for slowing of lesion growth in patients receiving fenretinide. This trend was particularly evident in patients in the 300 mg dose group who had substantial reductions in serum retinol and its carrier protein, retinol binding protein (RBP). Data from the 300 mg dose group demonstrated a reduction in median lesion growth when RBP and retinol levels were reduced by more than 50 percent. This finding supports the proof of concept that reduction of circulating RBP and retinol reduces lesion growth in patients with GA.

Full analysis of all lesion size measurements is ongoing. The complete data will be presented later this year at the annual meeting of the American Academy of Ophthalmology.

About ReVision Therapeutics

ReVision Therapeutics Inc. is an ophthalmic biopharmaceutical company developing a novel small molecule drug for the treatment and prevention of the dry form of age-related macular degeneration (AMD). Fenretinide (RT-101), ReVision's lead drug candidate, has been evaluated in a Phase 2b clinical trial in patients with geographic atrophy, the most advanced form of dry AMD. Analysis of the end-of-study data is ongoing. AMD is the leading cause of blindness in the elderly, and there are currently no treatments for the dry form of AMD, which accounts for 90 percent of patients with the disease. AMD gradually destroys sharp, central vision, and is caused by the accumulation of A2E, a toxic byproduct of the visual cycle, in the retina. Fenretinide reduces A2E accumulation in the retina by reducing systemic levels of retinol (vitamin A), a precursor to A2E. ReVision was founded in 2010 with corporate headquarters in San Diego, California. For more information, visit www.revisiontherapeutics.com

SOURCE ReVision Therapeutics Inc.