Retinal Physician

JAN-FEB 2017

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24 R E T I N A L P H Y S I C I A N . C O M | J A N U A R Y / F E B R U A R Y 2 0 1 7 R E T I N A L P H Y S I C I A N | J A N U A R Y / F E B R U A R Y 2 0 1 7 24 After an encouraging, but preliminary and uncon- trolled, small phase 1/2 clinical trial, Janssen has moved its proprietary cell therapy CNTO 2476 into the major 255-patient phase 2b PRELUDE study. Because there was a 15% incidence of retinal detachment in the earlier trial in which the human-derived umbilical cells were inserted by microcatheter, a new subretinal delivery kit and some changes in the surgical procedure have been implemented for the PRELUDE trial, says Allen Ho, MD, of Wills Eye Hospital, the lead investigator for both studies. In the earlier 35-patient trial, the mean BCVA gain at one year was more than four letters, while 25% of the patients gained three lines of vision or more. The aver- age vision loss at one year was two letters for untreated fellow eyes. As to whether he expected these preliminary results to be replicated in the larger trial, Dr. Ho says he is hopeful. Patients in the PRELUDE study will get a sin- gle injection of 60,000 cells, 300,000 cells, or sham. Cell therapy can have either a regenerative or trophic approach, says Dr. Ho. In the regenerative approach, the transplanted cells are meant to take the form of the dead or damaged native photoreceptor cells. With the trophic approach, the new cells are intended to support, repair, and rescue the native photoreceptor cells, but remain differentiated from the native cells. The PRELUDE study uses a tro- phic approach. Janssen selected human-derived umbilical cells for these studies because they were judged as having the best chance of being effective of the four cell types tested. PREVIOUSLY APPROVED ORAL DRUGS STUDIED FOR GA Clinical trials for GA are being conducted for three oral drugs that are FDA-approved for other indications. The National Eye Institute is conducting a study in which 40 patients will be given 100 mg of the antibi- otic Minocin (minocycline) twice daily for 36 months. Minocycline has demonstrated neuroprotective and anti-inflammatory properties in neurodegenerative dis- eases such as Parkinson's and Huntington's, and is being studied for potential use in Alzheimer's. The primary endpoint for this study is the rate of change in the area of GA at 24 and 36 months. Secondary endpoints include number of adverse events, change in BCVA, and change in low-luminance BCVA. Oracea (doxycycline) is an anti-inflammatory indi- cated for treatment of rosacea. Paul Yates, MD, PhD, of the University of Virginia, the University of Virginia Department of Ophthalmology, and the Medarva Foundation are conducting this ongoing, 206-person, 31-month study. The goal is to slow disease progres- sion. Patients take one 40 mg Oracea capsule daily for 24 months. The primary endpoint is the rate of enlarge- ment of the area of GA at 6 and 30 months. A secondary endpoint is change in BCVA at 6 and 30 months. Metformin (Glucophage, EMD Serono, Inc., Rockland, MD) a widely used first-line treatment for type 2 diabetes, belongs to the biguanide class of antidiabetic, sugar-lowering drugs. The University of California, San Francisco, is sponsoring a 100-patient, 18-month phase 2 study to determine if oral metformin can decrease the rate of GA progression in nondiabetic patients. Fifty patients will be given increasing doses of metformin and another 50 will be observed only. The metformin patients will start on a low dose to avoid gas- trointestinal discomfort. THEN THERE WAS ONE One drug that was tried but failed is Emixustat Hydrochloride, a visual cycle modulator from Acucela. This oral drug did not meet its primary endpoint in a phase 2b/3, 508-patient clinical trial earlier this year. Acucela had partnered with Otsuka (Princeton, NJ) for development of this drug, but that partnership has been terminated. Acucela said it is continuing to review the data from the trial. LOOKING AHEAD Drug researchers use the term "shots on goal" to discuss the number and variety of therapeutic approaches aimed at any specific disease. Their reasoning is that, with many varied concepts in play, it increases the chances of success in combating the disease. Given the myriad approaches described above, it's clear that researchers are serious about crashing the net. Only time will tell if any succeed with a breakaway. RP By increasing the number and variety of therapeutic approaches against any specific disease, so too do the chances of combating it. GEOGRAPHIC ATROPHY NOW IN RESEARCHERS' SIGHTS

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