NT-501 CNTF IMPLANT

 

Neurotrophic growth factors have been identified as potential therapeutics for neurodegenerative disease. Ciliary neurotrophic factor (CNTF) is one such candidate with strong preclinical evidence for retinal neuroprotection in several animal models that improves the survival and optic nerve axon regeneration of retinal ganglion cells (RGCs). Ciliary neurotrophic factor has been shown to increase retinal thickness in a dose-dependent manner in patients with age-related macular degeneration (AMD) and retinitis pigmentosa.

The NT-501 is a CNTF intraocular implant, being trialed for its role in neuroprotection and neuroenhancement in glaucoma. The implant has been developed by Dr. Jeffrey L. Goldberg, and his team at Stanford University, USA.

NT-501 consists of encapsulated human cells genetically modified (designated as NTC-201) to secrete CNTF.  Cells encapsulated in a semipermeable hollow fiber membrane continuously deliver a low, safe, and therapeutic dose of CNTF into the retina.

The Phase I study involved 11 participants diagnosed with primary open-angle glaucoma (POAG). One eye of each patient was assigned as the study (implant) eye and was implanted with a high-dose CNTF-secreting NT-501 implant, whereas the other eye served as a control. All patients were followed up for 18 months.

Visual acuity and contrast sensitivity decreased more in fellow eyes than in study eyes (VA, −5.82 vs. −0.82 letters; and contrast sensitivity, −1.82 vs. −0.37 letters, for fellow vs. study eyes, respectively). The median HVF visual field index and mean deviation measurements worsened (decreased) in fellow eyes (−13.0%, −3.9 dB) and improved (increased) in study eyes (2.7%, 1.2 dB). Implanted eyes showed an increase in retinal nerve fiber layer thickness measured by OCT and by GDx VCC (OCT, 2.66 μm vs. 10.16 μm; and GDx VCC, 1.58 μm vs. 8.36 μm in fellow vs. study eyes, respectively).

The NT-501 CNTF implant was safe and well tolerated in eyes with POAG. Eyes with the implant demonstrated both structural and functional improvements suggesting biological activity. A foreign-body sensation was the most commonly reported AE and was self-limited to the postoperative period. The most common implant-related AE was pupil miosis; no patients underwent explant.

The Phase II study is currently recruiting and will involve about 30 patients. The patients will be randomized to single implant, double implant, or sham implantation (nothing gets put inside the eye), but the patients are masked to which group they are in. After one year, the patients who were in the sham group will be offered an option to get the real implant.