NT-501 CNTF Renexus
Renexus® (NT-501) consists of encapsulated human cells genetically modified to secrete ciliary neurotrophic factor (CNTF). CNTF is a human growth factor that preferentially stimulates and protects neural cells - including photoreceptor cells responsible for detecting light in the retina of the eye. Renexus® is designed to continually deliver a safe and therapeutic dose of CNTF into the back of the eye for the treatment of retinal degenerative diseases. Neurotech is currently conducting several clinical trials with Renexus®, including clinical trials in patients with retinitis pigmentosa (RP), macular telangectasia (MacTel) and achromatopsia. Neurotech also collaborates with research ophthalmologists in investigator-initiated clinical trials for other neurotrophic ocular diseases.
A total of 184 patients enrolled across three Renexus® (NT-501) Phase 2 studies in the US, with some patients reaching past 50 months post-implantation. Renexus® continues to have a good safety profile. There have been no reported incidences of retinal detachment or increase in intraocular pressure associated with device implantation.
Phase 2 Retinitis Pigmentosa (RP) Trials
In May 2009, Neurotech announced the results of two Phase 2 clinical trials of Renexus® for the treatment of visual loss associated with RP—one trial consisting of patients with earlier stage disease (60 patients, NCT00447980) and the second trial consisting of patients with later stage disease (60 patients, NCT00447993). Both trials were randomized, multi-centered, double-masked, sham-controlled dose-ranging studies, designed to evaluate the efficacy and safety of Renexus® . Patients enrolled in these studies received either a high or low dose NT-501 implant in one eye and a sham-treatment in the fellow eye. BCVA was the primary efficacy endpoint for the late stage RP study and visual field sensitivity was the primary efficacy endpoint for the early stage RP study.
In both RP studies, there was a statistically significant (p<0.001 for the high dose group in each study), dose-dependent increase in retinal thickness involving photoreceptor layers as measured by optical coherence tomography (OCT) – also observed in the Phase 2 Renexus® GA study. RP patients generally have a gradual progression of vision loss due to photoreceptor degeneration, and often requiring up to 7 years for clinical manifestation, thus no trend in visual benefit or function was observed for either treatment or control groups within the first year time-point of the RP studies. Ongoing registration-extension studies are being conducted to monitor the long term, multi-year effects of Renexus® for RP patients.
Neurotech is currently conducting additional Renexus® clinical studies at University of California, utilizing AOSLO to monitor photoreceptor preservation and RP disease progression (NCT01530659). Recently, a longitudinal study using adaptive optics scanning laser ophthamoscopy (AOSLO) was applied to a sub-population of RP patients treated with Renexus® . High resolution AOSLO enables graphic enumeration of retinal photoreceptor cells, revealing statistically significant preservation of photoreceptors in those eyes treated with Renexus® , compared with eyes in the sham control groups over a 24-month period. These results suggest that AOSLO may offer an objective clinical evaluation of photoreceptor and retinal health in RP patients, especially those benefiting from Renexus® treatment.
Neurotech has received Orphan Drug designation and Fast Track designation for Renexus® for the treatment of visual loss in RP from the U.S. Food and Drug Administration.
Phase 1 Macular Telangiectasia (MacTel) Trials
Neurotech is conducting a phase 1 study (NCT01327911) using Renexus® for the treatment of patients with Macular Telangiectasia, an idiopathic condition that includes a vascular disorder of the macula, where juxtafoveal angiogenesis leads to loss of the central vision. Like RP, MacTel is a slow progressing disease, manifesting over a period of 10-20 years. The MacTel Project has identified CNTF as a potential modulator of vision loss in MacTel disease, and is collaborating with Neurotech in investigating potential benefit of long term Renexus® treatment.
Neurotech has received Orphan Drug designation for Renexus® for the treatment of Macular Telangiectasia from the U.S. Food and Drug Administration.
Phase 1 Achromatopsia Trial
Neurotech is conducting a phase 1 study at the National Eye Institute using Renexus® for the treatment of patients with achromatopsia. Achromatopsia is monogenic congenital retinal dystrophy that causes reduced visual acuity, extremely limited color vision discrimination, nystagmus and photophobia. It is inherited as an autosomal recessive trait. Currently there is no treatment for this condition. The objective of this study is to accumulate data on the safety of the intraocular Renexus® implant in participants with CNGB3 achromatopsia and to explore possible benefit of CNTF on visual function using standard clinical visual psychophysical and electrophysiological measures.
Phase 2 Dry Age-Related Macular Degeneration/Geographic Atrophy Trial
The Geographic Atrophy Phase 2 study (CNTF2, NCT00447954) was a randomized, multi-centered, double-masked, sham-controlled study designed to evaluate trends in efficacy and safety of NT-501. Patients received either a high or low dose Renexus® implant or a sham-treatment in one eye only. A change in best corrected visual acuity (BCVA) was the primary efficacy endpoint of this study. In March 2009, Neurotech announced that NT-501 substantially slowed the loss of vision in a Phase 2 clinical trial of 51 subjects with GA. In the study, the high dose of NT-501 stabilized BCVA at 12-month, with 96.3% (p=0.078) of treated-patients losing fewer than three lines of vision, or 15 letters, versus 75% of the patients in the sham-treatment group. The strong trend in visual acuity stabilization at 12 months was preceded by a dose-dependent, statistically significant (p<0.001 and p=0.013 for high and low dose, respectively) increase in retinal thickness as measured by optical coherence tomography (OCT) that was observed as early as four months post-implantation. The observed increase the thickness of the retina is consistent with preclinical studies of NT-501 in which CNTF was shown to increase the number and density of outer nuclear layer of photoreceptors responsible for vision. This increase in retinal thickness was associated with photoreceptor rescue and protection in numerous animal models of retinal degeneration.
Neurotech has received Fast Track designation for Renexus® for the treatment of visual loss associated with dry AMD from the U.S. Food and Drug Administration.