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
Data Presented at Annual Meeting of the American Society of Retinal Specialists Results Show Fenretinide's Dual Mechanisms of Action May Have Clinical Benefit in GA and Prevent CNV
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
Media Contact ------------- Heidi Chokeir, Ph.D. Russo Partners, LLC P (619)528-2217 M (858)380-6584 heidi.chokeir@russopartnersllc.com
Source: ReVision Therapeutics Inc.
CONTACT: Heidi Chokeir, Ph.D., Russo Partners, LLC,
+1-619-528-2217, M
+1-858-380-6584, heidi.chokeir@russopartnersllc.com,
for ReVision Therapeutics
Inc.
Web Site: http://www.revisiontherapeutics.com/
Posted: September 2010
