There are a range of treatments available to slow the progression of dry age-related macular degeneration, including nutritional supplements, injections and cell-based interventions.

Wet AMD occurs when abnormal blood vessels form and leak fluid into the retina, leading to permanent vision loss.

Faricimab-svoa (Vabysmo), approved by the FDA, works by inhibiting two disease pathways associated with wet age-related macular degeneration and diabetic macular edema, thus slowing its progression over two years. New 2-year data shows it does just that.

Syfovre® (pegcetacoplan injection)

Apellis Pharmaceuticals was granted FDA approval of their complement inhibitor injection, Syfovre(r), to treat geographic atrophy (GA) secondary to advanced dry AMD in February 2023 – making history by becoming the first drug approved to slow its progression, which leads to permanent vision loss. Syfovre(r) (pegcetacoplan) binds to components C3b and C3d to regulate excessive complement activation within the eye; two Phase 3 clinical studies, DERBY and OAKS showed its efficacy by reducing lesion growth while being safe and well tolerated by participants in its two Phase 3 clinical studies DERBY and OAKS respectively; safe and well tolerated outcomes were observed throughout these clinical studies.

Patients in this study received Syfovre injections every month or every other month and underwent regular exams to monitor changes to their visual acuity. Results of the research demonstrated that over 24 months, those receiving higher dosages saw the greatest reductions in GA lesions growth. It also concluded that its benefits lasted at least 18 months, an important measure of effectiveness when treating severe disease conditions.

Studies conducted to date have indicated that pegcetacoplan may be an effective option for individuals not responding to other treatments for GA, however numerous factors can impact its use for specific individuals; factors including age, cataract presence and suitability for other therapies intended to slow disease progression should all be taken into consideration before making this determination.

An annual eye exam is essential in spotting early signs of dry macular degeneration, which can be managed through lifestyle interventions and medical therapies. If you or a loved one are exhibiting symptoms of this condition, consulting with a retinal specialist would help identify new treatments which would benefit that individual. Molina Healthcare plans offer coverage for some of the latest and transformative drugs used to combat it such as Syfovre as part of our dry macular degeneration treatment 2023 program; contact your plan today to discover more!

Lytenava® (bevacizumab injection)

Food and Drug Administration (FDA) has granted bevacizumab (Lytenava(r), Roche) Priority Review status in order to treat age-related macular degeneration (AMD). A decision will be issued under Prescription Drug User Fee Act target date on Oct 19, 2023.

Bevacizumab proved effective against dry AMD in a study involving 30 eyes that still contained recoverable photoreceptor layers, improving best-corrected visual acuity by stabilizing mitochondria in retinal cells to protect optic nerve from further damage and slow progression of geographic atrophy, an increasingly prevalent symptom associated with dry AMD.

Risuteganib (Luminate, Allegro Ophthalmics LLC) is another promising late clinical development drug targeting the mitochondria by inhibiting GTPase activator type 1. This reduces abnormally high energy levels caused by mitochondrial oxidative stress, thus protecting cellular function and vision preservation. Both its safety and efficacy have been evaluated through a phase 2 trial.

Researchers have recently made an important discovery: Methotrexate can aid in the prevention of dry macular degeneration progression and retinal redetachment in people living with proliferative diabetic retinopathy, thus potentially eliminating laser treatment and other invasive therapies as necessary treatments. This finding may prove particularly significant.

Outlook Therapeutics recently announced that the FDA issued them a Biologics License Application (BLA) response letter regarding ONS-5010/LYTENAVA(r) (bevacizumab-vikg), an investigational ophthalmic formulation of bevacizumab for treatment of wet macular degeneration and other retinal diseases. This CRL included observations pertaining to manufacturing issues that could impact product quality as well as an insufficient supply of prefilled syringes suitable for filling, which they intend on working closely with FDA to address. As per this BLA submission with revised clinical program and additional data analysis.

Luminate® (risuteganib injection)

Orasis Pharmaceuticals announced in October 2023 that the FDA had granted approval of Qlosi (pilocarpine hydrochloride ophthalmic solution 0.4%), their new presbyopia drug. Qlosi works by blocking two signaling pathways linked to vision-threatening retinal conditions: Angiopoietin-2 and Vascular Endothelial Growth Factor A or VEGF-A are bound with by this medication preventing their actions; its expected to hit shelves by mid-2024 in America

Luminate is an anti-VEGF intravitreal injection targeting integrin receptors. Integrin proteins play an essential role in both physiological and pathological processes, including cell adhesion. Studies conducted using this drug have proven its efficacy against nonexudative age-related macular degeneration and diabetic macular edema (DME), with safety and tolerability established through phase 2 studies.

The study involved a double-masked, placebo-controlled trial utilizing 1.0 mg risuteganib in patients with nonexudative AMD. Its primary endpoint was measuring how many patients improved their best corrected visual acuity (BCVA) by at least eight letters between baseline and week 28; 48.0% in the risuteganib group achieved this goal versus 7.1% among sham group members.

An additional endpoint was to determine the percentage of subjects receiving risuteganib who experienced an eight-letter improvement or greater in their low-luminance BCVA at week 12. Of sham patients who achieved this, 14.3% attained this mark versus 20% among risuteganib patients; this difference between these groups was statistically significant (p = 0.013).

Geographic atrophy (GA), is one of the primary causes of vision loss among those with dry macular degeneration (DMD). It occurs when part of the retina at the back of the eye thinning due to age or certain risk factors like light-colored eyes or family history of disease – it also increases one’s risk for wet AMD (neovascular AMD).

Regeneron’s EYLEA (aflibercept) injection was approved by the Food and Drug Administration in January 2022.1 It can be used to treat wet age-related macular degeneration, macular edema after retinal vein occlusion and diabetic macular edema; additionally it may help treat retinopathy of prematurity in premature infants.

Aldeyra® (RASP modulator)

Aldeyra’s small molecule drug candidate reproxalap is designed to lower excessive RASP levels in the eye. Elevated levels are associated with inflammation and changes in tear lipid composition; during Phase III TRANQUILITY trial results released December 20,2021, reproxalap demonstrated significant improvements on one key secondary endpoint — an increased Schirmer test responder analysis that indicates increased tear production; however, its primary goal of reducing redness as an indication of dry eye disease was not met.

Due to this setback, Lexington-based company decided to conduct another trial using a modified protocol and statistical plan – Phase III TRANQUILITY-2 trial results published in June of 2022 demonstrated that reproxalap significantly reduced itching and redness during high pollen seasons – the source of allergic conjunctivitis symptoms – as well as showing clinically meaningful improvements in key secondary measures of the disease such as Ocular Itching Scale-derived redness scores.

Ophthalmology may experience significant change this year as new drugs hit the market and companies continue to push the envelope of what is possible. For a comprehensive coverage of major events happening within ophthalmology in 2023, be sure to follow Ophthalmology Times!

Aldeyra’s system-based drug discovery and development engine focuses on modulating immune responses that cause immune-mediated diseases. At present, Alcon’s ophthalmology pipeline includes ADX-246 and ADX-248, two investigational compounds which should move toward clinical testing once FDA Investigational New Drug (IND) requirements have been fulfilled. ADX-246 is a small molecule designed to relieve eye inflammation by inhibiting pro-inflammatory cell signaling pathways. ADX-248 is an advanced RASP modulator that may reduce accumulations of toxic metabolites that hinder dark adaptation during dry AMD, with plans underway to evaluate its impact in this patient population. A clinical trial is set for this treatment soon. Studies are based on data gleaned from preclinical and clinical trials of reproxalap, the company’s lead product. Replicalap is currently seeking an SPA with FDA and hopes to have feedback by December of 2023, with top-line trial results anticipated by early 2024.