Phase 2b Data Suggest ReVision's Oral Fenretinide (RT-101) Slows Lesion Growth, Preserves Vision and Reduces Incidence of Neovascularization in Geographic Atrophy Patients
Study Identifies Potential Biomarker That May Predict Treatment Response
Preliminary Analysis of Data from Phase 2b Study Presented at Annual Meeting of the American Academy of Ophthalmology
CHICAGO, Oct. 18 /PRNewswire/ -- ReVision Therapeutics Inc. today announced results from a Phase 2b trial suggesting that fenretinide (RT-101) slows lesion growth and preserves visual acuity in patients with geographic atrophy (GA), the most advanced form of dry age-related macular degeneration (AMD). The data showed that a sustained reduction in retinol binding protein (RBP) levels of 60 percent to 75 percent was predictive of positive treatment response to fenretinide. Patients receiving fenretinide who achieved this RBP reduction threshold experienced a ~49 percent slower rate of lesion growth compared to patients receiving placebo.
Visual acuity was also preserved in patients experiencing a sustained RBP reduction. Additionally, fenretinide reduced the incidence of CNV, the more sight-threatening wet form of AMD, by about 40 percent. Taken together, these results suggest that once-daily oral dosing of fenretinide has the potential to slow progression of dry AMD and prevent the onset of wet AMD in GA patients.
"We are very encouraged because these data demonstrate that fenretinide may improve clinical outcomes for patients with both the dry and wet forms of AMD," said Jason Slakter, M.D., clinical professor of ophthalmology at New York University School of Medicine, who evaluated the lesion image data for the trial and presented the study results yesterday at the Annual Meeting of the American Academy of Ophthalmology. "Additionally, for the first time ever, we may have a biomarker to predict patient response to therapy, as approximately one-third of the patients who achieved a profound and sustained reduction in RBP levels experienced a beneficial treatment effect. I am looking forward to future studies to confirm these results and determine the role fenretinide may play in treating our patients."
The double-masked, placebo-controlled, multicenter, Phase 2b study evaluated 246 patients with GA. Patients were randomized into three cohorts and received once-daily, oral 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, the incidence of choroidal neovascularization (CNV) and serum RBP levels. This is the largest study to date for an oral therapeutic agent for treatment of GA. Fenretinide was well tolerated with no severe drug-related adverse events and no significant effects on normal visual function.
Analysis of the lesion and RBP data at the conclusion of the two-year study showed that 43 percent of patients in the 300 mg fenretinide arm had a sustained RBP reduction of at least 60 percent throughout the trial. Those patients had a median lesion size growth of only 30 percent from baseline, compared to a median lesion size growth of about 50 percent in the placebo arm. Visual acuity loss in patients who experienced reduced lesion size growth was stabilized from 12 months to 24 months at six letters lost, while patients in the placebo arm showed progressive loss throughout the trial reaching an average loss of 11 letters at 24 months.
At the conclusion of the two-year study, the incidence of CNV in the placebo arm was 22 percent. Meanwhile, CNV incidence in patients receiving either dose of fenretinide was ~13 percent to 14 percent. The comparable therapeutic effect at both low and high doses of fenretinide suggests a mechanism of action that is not dependent upon reduction of serum RBP.
The accumulation of retinol (vitamin A)-derived toxins in the eye is believed to exacerbate lesion growth leading to progression of GA. Inflammation and induction of angiogenic mediators has been implicated in risk and progression of wet AMD. Fenretinide limits the delivery of retinol to the eye through reduction of serum RBP. This slows the accumulation of retinol-derived toxins in the retina, thereby slowing lesion growth. The anti-inflammatory and anti-angiogenic properties of fenretinide are thought to provide an additional therapeutic benefit against development of wet AMD.
About ReVision Therapeutics
ReVision Therapeutics Inc. is an ophthalmic biopharmaceutical company developing a novel small-molecule drug to slow the progression of the dry form of age-related macular degeneration (AMD) and prevent wet AMD. Fenretinide (RT-101), ReVision's lead drug candidate, showed a positive treatment effect for both slowing lesion growth in dry AMD and reducing the incidence of wet AMD in a Phase 2b clinical trial in patients with geographic atrophy, the most advanced form of dry AMD. The company plans to initiate a pivotal Phase 3 trial after discussion with the FDA. 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. Dry AMD gradually destroys sharp, central vision. Most cases of wet AMD are preceded by dry AMD, and the onset of wet AMD can cause rapid blindness. ReVision was founded in 2010 with corporate headquarters in San Diego, California. For more information, visit www.revisiontherapeutics.com
SOURCE ReVision Therapeutics Inc.
Chokeir, Ph.D., Russo Partners, LLC for ReVision Therapeutics Inc.,
Web Site: http://www.revisiontherapeutics.com
Posted: October 2010