Neurotech Pharmaceuticals, Inc., today announced that, as reported in Investigative Ophthalmology & Visual Science (April, 2011, Vol. 52), the Company’s product candidate NT-501 demonstrated statistically significant cone photoreceptor preservation in patients with retinitis pigmentosa (RP)-a slowly developing condition that causes the progressive bilateral degeneration of photoreceptor cells in the retina, eventually resulting in blindness. NT-501 is an intraocular implant that consists of human cells genetically modified to secrete ciliary neurotrophic factor (CNTF)-a nerve growth factor capable of rescuing and protecting dying photoreceptors. The study utilized Adaptive Optics Scanning Laser Ophthalmoscopy (AOSLO), a breakthrough diagnostic technology, to image and measure the rate of the progressive degeneration of cone photoreceptors. AOSLO overcomes a major obstacle in the study of retinal degeneration-the non-invasive measurement of cone photoreceptor cells and their rate of degeneration in the eyes of living subjects.
“Given the slow progression of these diseases, measuring improvements in visual function appears to require extremely lengthy trials. We believe tools such as AOSLO that measure photoceptor preservation can play an important role in defining meaningful and measurable near-term benefits of treatment of such slow-progressing, debilitating diseases”
In the prospective study, two patients with RP and one patient with Usher syndrome type 2, a rare genetic disorder characterized by vision loss due to RP and bilateral hearing loss, were evaluated by AOSLO at baseline and at 3, 6, 12, 18 and 24 months following implantation. Patients studied were selected from Neurotech’s Phase 2 NT-501 study in patients with early-stage RP. For each patient, one eye received an NT-501 implant while the fellow eye received sham-treatment. AOSLO quantitatively assessed photoreceptor loss by measuring cone density and average cone spacing at several prospectively identified locations in the retina of each patient, aggregating repeated measures for all data points, and comparing results for the active- and sham-treated eyes. No increase in cone spacing or decrease in cone density was observed in any of the eyes treated with NT-501. An increase in cone spacing and a decrease in cone density are both indicative of photoreceptor loss. In addition, the results demonstrated a statistically significant preservation of cone photoreceptors in the eyes of all three subjects treated with the NT-501 implant versus sham-treated eyes. Cone spacing increased by 2.9% more per year in sham-treated eyes than in NT-501-treated eyes (p < 0.001), and cone density decreased by 9.1% more per year in sham-treated eyes than in NT-501-treated eyes (p = 0.002).
The study was led by Jacque Duncan, MD, Professor of Clinical Ophthalmology, University of California, San Francisco, and Austin Roorda, PhD, Professor of Optometry and Vision Science, Chair and Head Graduate Advisor in the Vision Science Program, University of California, Berkeley. Dr. Duncan commented, “We are extremely encouraged by the photoreceptor preserving effect of NT-501 seen in this study as well as the usefulness of AOSLO as a diagnostic tool for retinitis pigmentosa progression. Larger studies using AOSLO are urgently needed to confirm the photoreceptor protective effect of NT-501 treatment in patients with retinal degeneration.”
Paul Sieving, MD, PhD, Director of the National Eye Institute and Principal Investigator of Neurotech’s Phase 1 study of NT-501 in RP commented, “These results suggest that AOSLO may play a meaningful role in the early assessment of photoreceptor loss due to retinitis pigmentosa well before serious functional loss is detected by standard measures of visual function, and that NT-501 may play an important neuroprotective role.”
“These exciting results add to the growing body of evidence that NT-501 will benefit individuals who suffer from retinitis pigmentosa and other retinal degenerative diseases,” stated Ted Danse, Chief Executive Officer of Neurotech. “Given the slow progression of these diseases, measuring improvements in visual function appears to require extremely lengthy trials. We believe tools such as AOSLO that measure photoceptor preservation can play an important role in defining meaningful and measurable near-term benefits of treatment of such slow-progressing, debilitating diseases,” added Danse.
About RP and Usher Syndrome
Retinitis Pigmentosa (RP) is an inherited disease that causes the retina’s rod and cone photoreceptors to gradually degenerate leading to loss of vision and blindness. The symptoms of RP predominately appear in young adults and affect approximately 100,000 people in the United States and over 1 million people worldwide. Currently there are no approved treatments for RP. Usher syndrome is a rare genetic disorder that is a leading cause of deafblindness and is characterized by vision loss due to RP and bilateral congential hearing loss. Hearing loss in Usher Type 2 generally involves people who are not born deaf, but gradually lose their hearing.
NT-501 is one of Neurotech’s lead product candidates under development and consists of encapsulated human cells genetically modified to secrete ciliary neurotrophic factor (CNTF). CNTF is a nerve growth factor capable of rescuing dying photoreceptors and protecting them from degeneration. NT-501 is designed to continually deliver a therapeutic dose of CNTF directly to the back of the eye in a controlled, continuous manner by means of the Company’s proprietary Encapsulated Cell Therapy (ECT) platform. Delivery via ECT bypasses the blood-retinal barrier and overcomes a major obstacle in the long-term treatment of retinal disease. NT-501 has received orphan and fast-track designations for the treatment of visual loss in RP from the United States Food and Drug Administration (FDA).
AOSLO technology is able to image cone photoreceptors, those cells of the retina responsible for fine central and color vision, and quantitatively measure the changes in those cones over time. Standard clinical imaging techniques cannot visualize individual photoreceptors due to optical imperfections in living eyes. Scanning laser ophthalmoscopy (SLO) is a method of diagnostic imaging of the eye that uses confocal imaging to obtain high-resolution optical images at varying depths within the eye. The use of adaptive optics (AO) improves SLO by removing aberrations in retinal images caused by imperfections in the eye’s optics. The improved image makes it possible to see individual cone photoreceptor cells non-invasively in the eyes of living subjects.
About Encapsulated Cell Therapy
Neurotech’s core technology platform is Encapsulated Cell Therapy (ECT), a unique technology that allows for the long-term, sustained delivery of therapeutic factors to the back of the eye. ECT implants consist of cells that have been genetically modified to produce a specific therapeutic protein and are encapsulated in a semi-permeable hollow fiber membrane. The diffusive characteristics of the hollow fiber membrane are designed to promote long-term cell survival by allowing the influx of oxygen and nutrients while simultaneously preventing direct contact of the encapsulated cells with the cellular and molecular elements of the immune system. The cells continuously produce the therapeutic protein which diffuses out of the implant at the target site. ECT enables the controlled, continuous delivery of therapeutic factors directly to the retina, thereby bypassing the blood-retina barrier.
Neurotech Pharmaceuticals, Inc.