Table 1.
Clinical trials and other approaches to treat dry AMD and GA.
| Drugs/nature | Route of delivery (aim/mechanisms of action) | Sponsors | Clinical phase | Clinicaltrial.Gov identifiers (year of completion) |
|---|---|---|---|---|
| Visual cycle modulators | ||||
| Fenretinide (retinol analogue) | Oral (inhibits binding of retinol) | Sirion Therapeutics | II | NCT00429936 (2010) |
| Emixustat HCl (ACU-4429) SEATTLE | Oral (non-retinoid, inhibits RPE65, blocking conversion of retinol into 11-cis retinal) | Acucela |
II II/III |
NCT01002950 (2014) NCT01802866 (ongoing) |
| ALK-001 (a modified form of vitamin A) | Oral (forms vitamin A dimers slowly) | Alkeus Pharmaceuticals, Inc. | III | NCT03845582 (2022) |
| Suppressors of inflammation and complement activation | ||||
| RN6G |
IVI (binds and eliminates amyloid β) |
Pfizer | I |
NCT00877032 (2015) NCT01003691 (2013) |
| GSK 933776 |
IVI (binds and eliminates amyloid β) |
Glaxo Smith Kline | II | NCT01342926 (2016) |
| GAL-101 (investigational) | Oral (prevents misfolded amyloid β from aggregating into toxic forms in vitro) | Galimedix Therapeutics | II | NA |
| ARC1905 (anti-C5 Aptamer) | IVI (inhibits generation of C5a and MAC). | Ophthotech Corp | I | NCT00950638 (2012, unpublished) |
| Lampalizumab | IVI (mAb against complement factor D) | Chroma and Spectri, Genentech | III | NCT02247531 (terminated in 2018) |
|
Eculizumab (Soliris)/ the COMPLETE study |
iv (mAb against C5, inhibits its cleavage into C5a and C5b and MAC formation) | Alexion Pharmaceuticals | II | NCT00935883 (2013) |
| LFG316 (tesidolumab) | IVI (mAb against C5) | Novartis | II | NCT01527500 (2015, unpublished) |
| LG561 as a monotherapy and in combination with LFG316 | IVI (to reduce progression of GA) | Alcon Research | II | NCT02515942 (2017) |
| Pegcetacoplan (APL-2, a C3 inhibitor) | IVI (prevents C3 cleavage and cell lysis) | Apellis Pharmaceuticals | II | NCT02503332 (2018) |
| Doxycycline (ORACEA®, TOGA) | Oral (suppression of low-grade inflammation) | Paul Yates, University of Virginia | II/III | NCT01782989 (2020) |
| GEM103, full-length recombinant complement factor H protein | IVI (complement modulator; safety and tolerability of a single dose) | Gemini Therapeutics, Inc. | I | NCT04246866 (2020) |
| Zimura (anti-C5 aptamer) | IVI (to halt progression of GA) | IVERIC bio, Inc. | II/III | NCT02686658 (2020) |
| Stem cells | ||||
| CNTO 2476 (umbilical-cord-derived stem cells) | SRT (safety and response to improve visual acuity) in patients with GA | Janssen Research & Development, LLC | I/II | NCT01226628 (2017) |
| MA09-hRPE | SRT (safety and tolerability of hESC-derived RPE cells) |
Astellas Pharma Inc CHABiotech CO., Ltd |
I/II I/IIa |
NCT02463344 (2019) NCT01674829 (2020) |
| OpRegen | SRT (safety and tolerability of hESC-derived RPE cells under dose-escalation) | Lineage Cell Therapeutics, Inc. | I/IIa | NCT02286089 (2024) |
| GT005 (recombinant AAV that encodes a human complement factor I, FocuS) | SRT (increases production of the complement factor I, safety and efficacy of three doses) | Gyroscope Therapeutics | I/II | NCT03846193 (recruiting, 2025) |
| AAVCAGsCD59 | IVI (increases the expression of a soluble form of CD59, safety and efficacy of three doses) | Hemera Biosciences | I | NCT03144999 (2019) |
| iPSC-derived RPE | SRT (safety and efficacy data for future studies) | National Eye Institute (USA) | I/IIa | NCT04339764 (recruiting; 2029) |
| Antioxidants, mitochondrial enhancers and PBM | ||||
| Age-related Eye Disease Study (AREDS) 2 formulation |
Oral (AREDS formulation + lutein + zeaxanthin + docosahexaenoic acid + eicosapentaenoic acid), to reduce the risk of progression to advanced AMD Secondary goal: to test the effects of eliminating β-carotene and reducing zinc content in AREDS formulation. |
National Eye Institute (USA) | III | NCT00345176 (2012) |
| NT-501 (encapsulated human RPE-derived cells releasing CNTF) | IVI (to rescue photoreceptors) | Neurotech Pharmaceuticals | II | NCT00447954 (2011) |
| Brimonidine tartrate (α-2 adrenergic receptor agonist) | IVI (to reduce apoptosis) | Allergan | II | NCT00658619 (2013) |
| Omega-3 fatty acids (MADEOS; antioxidants) | Oral (to see therapeutic potential) | Ophthalmos Research and Education Institute, Cyprus | NA | NCT03297515 (2020) |
| Curcumin (Longvida curcumin; antioxidant) | Oral (to see impact on drusen volume) | University of Illinois at Chicago | I | NCT04590196 (recruiting; 2021) |
|
MTP-131 (Ocuvia™, ophthalmic solution) MTP-131 (elamipretide) ReCLAIM-2 study |
Topical (targets cardiolipin and preserves mitochondrial functions) Subcutaneous injection daily for 48 weeks |
Stealth BioTherapeutics Inc. |
I/II II |
NCT02314299 (2015) NCT03891875 (2022) |
| Metformin |
Oral (activates mitochondrial PGC-1α, efficacy in non-diabetic patients with GA) |
University of California, San Francisco | II | NCT02684578 (recruiting; 2021) |
| PBM |
670-nm LED light (activates cytochrome C oxidase; to increase ATP generation and improve mitochondrial function) 590, 670 and 790-nm LED light (to reduce drusen volume) |
[32, 33, 108] |
NA NA |
NA NA |
| PBM (The Valeda™ Light Delivery System, LIGHTSITE III | 590, 660 and 850-nm LED light (safety and efficacy in dry AMD) | LumiThera, Inc. | NA | NCT04065490 (2022) |
AAV adeno-associated viral vector, iv Intravenous, IVI intravitreal injection, iPSC induced pluripotent stem cell, hESC human embryonic stem cells, mAb monoclonal antibody, NA not applicable, SRT subretinal transplantation.