Tuesday, November 19, 2013

AMD Update 25: Results of The AREDS2 HOME Study of Notal Vision’s Home Monitoring Device for AMD Announced

In April of 2010, I wrote about the inclusion of Notal Vision’s ForseeHome AMD Monitor in the AREDS2 clinical trial.

The overall objective of the two arm randomized clinical trial was to determine if home monitoring of participants at high risk of progression from late-stage dry AMD to neovascular AMD, using the comprehensive visual field and telemedicine solution based on the ForeseeHome Device in AREDS2 (referred to as the ForeseeHome comprehensive solution), would improve detection of progression to choroidal neovascularization (CNV) when compared with standard care (may have included use of the Amsler Grid).

Well, the results are in and the National Institute of Health (NIH) found that patients at high-risk for developing neovascular age-related macular degeneration would benefit from using the ForeseeHome Monitoring device for early detection of their CNV.

Report Represents the Most Comprehensive Study of Home Monitoring for Progression of AMD

As reported at the Retinal Subspecialty Meeting at this year’s AAO Meeting, the results of the Home Monitoring of the Eye (HOME) study, conducted in Age-Related Eye Disease Study 2 (AREDS2) clinical centers showed that participants at high risk for developing choroidal neovascularization (CNV) using the ForeseeHome monitoring device strategy had significantly better preservation of their visual acuity at the time of CNV detection than the control group of participants who were only using standard care methods (the Amsler grid) to self monitor their AMD for progression. The study's Data Safety and Monitoring Committee recommended early termination of the study on April 2, 2013 based on superior vision outcomes among the participants randomly assigned to use the home device.

The AREDS2 HOME Study was a collaborative effort led by the National Eye Institute to evaluate the performance of a home monitoring device plus standard care compared to standard care monitoring alone for the detection of AMD progression to the neovascular phase. Standard care methods included periodic monocular self checks of vision clarity, blind spots and distortion, which included use of an Amsler grid. As treatments to manage the neovascular phase of AMD have improved, the importance of early detection of this event has increased in an effort to optimize outcomes following treatment of neovascular AMD. Approximately 8 million individuals in the United States, age 50 and older, are estimated to have intermediate (large drusen) or advanced dry AMD in one eye, placing them at high risk of progression to neovascular (wet) AMD (CNV), ranging from 25 to 50% over a five-year period.

Results of the HOME Study and Implications for AMD Management

At the time of CNV detection, 87% of eyes in the ForeseeHome device arm maintained visual acuity of 20/40 or better compared to 62% in the standard care alone arm. Median acuity among device users at the time of CNV diagnosis was 20/32. Among participants who used the device at the recommended minimum frequency (twice per week) to monitor their AMD for progression, 94% of eyes that progressed to CNV maintained 20/40 or better visual acuity. When CNV was detected, participants in the ForeseeHome device arm lost fewer letters on visual acuity testing (median loss of 4 letters) from entry levels of vision at the start of the study compared to those in the standard care alone arm (median loss of 9 letters). Use of the ForeseeHome device resulted in an increase in the proportion of CNV events first identified at home, meaning in between routine ophthalmic office visits to assess detection of disease progression. Among individuals using standard care methods for monitoring, only 55% of those that progressed noted symptoms at home that led them to present for examination; whereas 80% of the participants in the device monitoring group returned sooner than a scheduled visit because a change was noted by the device or by self-monitoring. This was associated with a greater degree of vision preservation at CNV diagnosis among individuals who returned promptly for changes, as the median visual acuity loss at CNV detection was 3.0 letters for those in the device arm compared with 11.5 letters for those in the standard care group. The average annual rate of false alerts among the device users, reported as the annual false positive rate, was 0.24 alerts/year, which may be extrapolated to one false alert on average every 4.2 years for each ForeseeHome user.

"Persons 60 years of age or older should undergo dilated eye examinations to determine their risk of developing advanced AMD, especially CNV," said Jeffrey S. Heier, MD, Director of the Vitreoretinal Service and the Director of Retina Research at Ophthalmic Consultants of Boston and one of the principal investigators of the HOME Study. "In contrast to current home monitoring strategies, those with intermediate AMD (bilateral large drusen) or advanced AMD in 1 eye are likely to benefit from home monitoring with the ForeseeHome device to detect the development of CNV at an earlier stage with better preservation of their visual acuity to maximize visual acuity results after intravitreal therapy with anti-VEGF agents."

About the HOME Study

The HOME Study was a controlled, randomized clinical trial that was part of AREDS2. The study was conducted in 44 clinical centers across the U.S., enrolling 1,520 participants at high risk for developing CNV. (With approximately half using the device and the other half acting as controls, using standard care.) The objective of the HOME Study was to determine whether monitoring with the ForeseeHome device plus standard care results in earlier detection of CNV compared to standard care alone. Standard care included instructions to the patient on self-monitoring for CNV. Better visual acuity at the time of CNV detection is both a reflection of earlier CNV detection as well as a favorable predictor for visual function outcomes following the management of CNV with intraocular anti-angiogenic medications.

The results of the study are now online, as published in Ophthalmology.

About the ForeseeHome AMD Monitoring Program

The ForeseeHome AMD Monitoring Program is a prescription-based, comprehensive telemonitoring and data management system that extends the management of AMD to patients' homes between office visits. The test results are transmitted to a central monitoring center that will alert, physicians to immediate, significant visual field changes in their patients, so that patients can be recalled for timely follow-up and necessary treatment may be initiated. The ForeseeHome AMD Monitoring Program utilizes a simple to use device based on preferential hyperacuity perimetry, a form of visual-field testing, to identify minute visual distortions, or metamorphopsia, for the detection of early CNV development.

To read more about Notal Vision and the ForseeHome device, read my full report of March 9, 2010: Notal Vision: The ForeseeHome AMD Monitor and It’s Potential to Save Vision – A First Report.

AMD Update 24: DARPins Phase 2 Trial Results Fall Short

Back in February, I first reported on Allergan’s DARPins in my Update 23: DARPins, The Next “Game Changer” for Wet AMD? In that report, I wrote that Molecular Partners’ MPO112 (Allergan’s AGN-150998) showed promise of improving vision and having a long ocular half-life which appeared to be a vast improvement over both Lucentis and Eylea, perhaps requiring injections every 3-4 months compared to bi-monthly for Eylea and monthly for Lucentis and Avastin. (I also noted a second agreement with Molecular Partners, the licensors of the DARPin technology to Allergan, in which a combination dual action anti-VEGF/PDGF drug therapy was also under investigation.)

Well, the first part of the promise, the longer interval injection rate for the DARPins, has fallen through. As reported by two analyst groups, Allergan presented results last Friday (November 15th) from the Phase 2 trial of AGN-150998 (anti-VEGF DARPin program) in wet AMD at the Retina Subspecialty Meeting ahead of the start AAO annual conference in New Orleans. The results supported the company's decision several months ago, to slow down advancement of the clinical trial, in that the drug failed to meaningful delay the time to retreatment and the associated rates of inflammation were higher than were anticipated. Though Allergan continues to evaluate the drug and still may ultimately advance it into Phase 3 studies, there appears to be only limited competitive threat to Eylea (or, perhaps Fovista, Ophthotech’s combination anti-VEGF/PDGF drug in clinical study – see my two write ups on Fovista, shown below, for more information about this potential drug). Specifically, the analysts see a low likelihood of commercial adoption or integration into the treatment paradigm for wet AMD without any sustained improvement in visual acuity or meaningful delay in the time to retreatment.

In looking at the data presented, the study evaluated two doses of the AGN-150998 (3mg and 4.2mg) vs. Lucentis. The drug was administered at week 4 and then pro re nata (PRN) or by week 16, and then again PRN or by week 32 at the latest. At day 60 and day 90, the 4.2mg dose appeared to delay the need for retreatment in ~10-15% of patients. Looking at the data another way, the 4.2mg dose appeared to delay the median time to retreatment by ~20 days. There were no differences in the percent of patients gaining 15 or more letters in best corrected visual acuity (BCVA) from baseline by week 16, and again at week 32.

In terms of safety, the AGN-150998 treatment was associated with a meaningful rate of ocular inflammation adverse events relative to Lucentis (13% vs. 0%). Specifically, treatment with AGN-150998 had higher rates of uveitis (3% with 3mg, 6% with 4.2mg, 0% with Lucentis), anterior chamber inflammation (2% and 3% vs. 0%), vitritis (7% and 2% vs. 0%).  For reference purposes, historical data imply the rate of intraocular inflammation in AMD trial are 13% and 1% with Lucentis and Eylea, respectively.

Allergan has indicated that it would be making changes to the manufacturing process to hopefully reduce the inflammation seen in the Phase 2 trials, when and if they decide to proceed to a Phase 3 trial.

I was not able to determine if Allergan and Molecular Partners still plan to go ahead with a clinical trial for the dual action drug, which remains in a pre-clinical stage.


Analyst Reports - Private correspondence.

Fovista Reports: