|Aerie||First-in-human study evaluating an aVEGF implant that may last 6 months|
|TENAYA||Phase III trial evaluating faricimab, a q16 week aVEGF injection|
|PANDA-2||Phase IIIb trial evaluating a biosimilar to Eylea|
|Talon||Phase IIIb trial evaluating brolucizumab, a q12 week aVEGF injection|
|Samsung||Phase IIIb trial evaluating a biosimilar to Lucentis|
|Graybug||Phase IIb trial evaluating a potential 6-month aVEGF depot injection|
|Oxygen study||Proof-of-concept study looking at enhancing visual transduction in patients with dry AMD|
Geographic atrophy due to AMD
|Apellis||Phase III trial evaluating an anti-complement injection to slow GA growth|
|IONIS||Phase II trial evaluating a subcutaneous injection to slow GA growth|
|GALLEGO||Phase II trial evaluating an anti-complement injection to slow GA growth|
|SCOPE||Natural history study evaluating GA growth relative to patient genotype|
|ASTELLAS||Phase II surgical trial evaluating subretinal stem cells for GA (upcoming)|
Diabetic macular edema
|Yosemite||Phase III trial evaluating faricimab, a q16 week aVEGF injection|
|Kingfisher||Phase IIIb trial evaluating brolucizumab, a q12 week aVEGF injection|
|RGX-314||Gene therapy study that may eliminate or greatly reduce the need for aVEGF injections|
|FOCUS||Phase III trial comparing the effects of systemic semaglutide to placebo on diabetic retinopathy progression|
Geographic atrophy associated with Macular Degeneration
Currently we have no treatment options for geographic atrophy (GA), which can cause devastating and permanent loss of central vision once the fovea is involved. GA leads to irreversible RPE cell death with secondary dysfunction of the overlying retina. The complement cascade is involved in this process, and most current studies are targeting this. If effective, the medications being investigated will not improve vision, but will hopefully slow down vision loss. This is particularly important in monocular patients. Future studies will be looking at stem cell and other therapies to potentially repair the area of damage.
The basic study criteria:
- GA due to AMD
- Age >/= 50
- VA 20/320 or better
- GA size between 1 and 7 disc areas
- GA not contiguous with peripapillary atrophy
- No history of intravitreal injections in that eye
- No eye surgery within 3 months
Derby/Oaks (Apellis Pharmaceuticals) – a 30-month, phase III, randomized, double-masked, sham-controlled study evaluating the safety and efficacy of APL-2. The phase II trial showed a 20% reduction in GA lesion size with monthly injections of APL-2, which is a complement C3 inhibitor. Patients are seen monthly for 30 months and will either receive a sham injection or APL-2. Transportation is covered, all study expenses are covered by the sponsor (insurance does not matter), and patients are given a small stipend for participating.
GALLEGO (Genentech, Inc) – a 12-month, phase II, multicenter, randomized, double-masked, sham-controlled study evaluating the safety and efficacy of intravitreal FHTR2163 given every 4 or 8 weeks compared to sham.
ISIS (IONIS Pharmaceuticals) – a phase II, randomized, double-masked, sham-controlled study evaluating the safety and efficacy of IONIS-FB-LRX, an antisense inhibitor of complement factor B. This study is unique in that the drug is given as a subcutaneous injection.
SCOPE (Gyroscope Therapeutics) – a multi-center natural history study to evaluate the progression of anatomical and functional parameters in genetically defined patients with GA due to AMD. Patients will be in one of two groups, subjects with complement factor I haploinsufficiency and subjects with all other complement variants. The study will consist of 7 visits over 24 months, with the potential for patients to be transferred into an interventional gene therapy study following the natural history study.
AIRM (Astellas Pharma Inc.) – an upcoming phase II study evaluating the safety and efficacy of subretinal delivery of pluripotent stem cells in the treatment of GA associated with AMD.
Dry macular degeneration
A common clinical feature of dry macular degeneration is reduced rod photoreceptor function associated with an abnormal visual cycle. This manifests at impaired scotopic visual function, and can be quantified with a dark adaptometer. We believe that visual transduction can be enhanced using supplemental oxygen.
Under the lead of Anne Hanneken, MD, we are enrolling patients in a prospective, non-randomized, proof-of-concept study to evaluate the effect of supplemental oxygen on dark adaptation scores.
Wet macular degeneration
Our current wet AMD medications do an excellent job of controlling wet AMD through repeated intravitreal injections of vascular endothelial growth factor (VEGF)-inhibitors. Next-generation medications are currently being studies that promise to extend the interval between treatments to every 4 to 12 months.
Basic study criteria:
- Age >/= 50
- Treatment-naïve wet AMD
- Involvement of the center of the macula
- VA 20/32 to 20/320
TENAYA (Genentech, Inc) – a 24-month, phase III, randomized, double-masked study evaluating the safety and efficacy of faricimab. This is not a sham-controlled study, patients in the control arm will receive aflibercept (Eylea), which is one of the current FDA-approved anti-VEGF medications. Faricimab is an exciting molecule that is designed to inhibit VEGF as well as a second vascular growth factor, angiopoetin-2. The expectation is that faricimab will be able to be dosed every 4 months instead of every 4-8 weeks like current medications. This is an excellent study and enrollment is filling quickly.
AERIE (Aerie Pharmaceuticals) – this is a 6-month, first-in-human study of the safety of AR-13503 sustained-release intravitreal implant in subjects with wet AMD and diabetic macular edema (DME). The hope in this study is that the implant lasts up to 6 months.
PANDA-2 (Chengdu Kanghong Biotechnology) – a 24-month multicenter, double-masked, randomized, dose-ranging study to evaluate the efficacy and safety of intravitreal conbercept in subjects with wet AMD. This drug is a biosimilar to one of our current gold-standard medications, aflibercept (Eylea), but should be considerably more cost-effective.
TALON (Novartis Pharmaceuticals) – a 16-month multicenter, randomized, phase IIIb study evaluating the safety and efficacy of brolucizumab vs. aflibercept in a treat-to-control regimen in patients with wet AMD. Brolucizumab is a next-generation aVEGF medication that should be available later this year. It will likely be dosed less frequently than current medications – every 12 weeks or longer in 50% of patients in the prior phase III study.
Samsung (Samsung) – a phase IIIb study evaluating the safety and efficacy of a medication biosimilar to the current FDA-approved aVEGF medication, ranibizumab (Lucentis).
ALTISSIMO (Graybug Vision, Inc.) – a phase IIb multicenter dose-ranging study evaluating the safety and efficacy of a long-acting intravitreal sunitinib malate depot formulation (GB-102) compared to intravitreal aflibercept in subjects with neovascular AMD. It is believed that the depot will last approximately 6 months.
Diabetic macular edema
Diabetic macular edema (DME) is typically more stubborn than wet AMD, but is often treated with similar medications. Most of the studies for new wet AMD drugs will also be looking at those drugs in patients with DME, including faricimab, AR-13505, and brolucizumab.
Basic study criteria:
- Age >/= 18
- Hemoglobin A1c less than 10%
- Macular edema secondary to DME
- DME involving the center of the fovea
- Central retinal thickness greater than 300uM
- VA 20/40 to 20/320
- No high-risk PDR in the study eye
Diabetic retinopathy (DR) refers to the visible manifestations of diabetes in the retina, including intraretinal hemorrhages, venous beading, intraretinal microvascular abnormalities, and neovascular tissue growth. Anti-VEGF medications are effective in reversing these abnormalities, and the risk of vision loss due to DME, vitreous hemorrhage, and retinal detachment. Most of the studies evaluating new aVEGF medications will also look at their efficacy in DR.
- Age >/= 18
- DR secondary to diabetes mellitus
- HbA1c </= 10%
- Moderate-severe NPDR to mild PDR
- VA 20/40 or better
RegenexBio – One of the more exciting trials that we will be participating in this fall is a phase II surgical gene therapy study from REGENEXBIO, Inc. In this open label, 6-month, proof-of-concept study eligible patients would be randomized to receive one of two doses of subretinal RGX-314. RGX-314 is a gene therapy product that uses an adenovirus vector to transfect surrounding cells, primarily RPE in this case, with the DNA to manufacture an anti-VEGF protein which is very similar to ranibizumab (Lucentis). So, the eyes will produce their own drug. This study on DR will look at the proportion of patients with a 2-step DR regression at 6 months, comparing the two doses.
FOCUS (Novo Nordisk) – a 5-year international, multicenter, randomized, phase III clinical study which is evaluating the safety and efficacy of semaglutide on the development and progression of diabetic retinopathy when added to standard of care for patients with type II diabetes. Semaglutide is a human glucagon-like peptide-1 (GLP-1) agonist that increases the secretion of insulin and can be delivered as a subcutaneous injection on a weekly basis. The clinical trial is being coordinated with The Whittier Diabetes Institute at Scripps Health.