New treatments provide hope to patients suffering from geographic atrophy (GA), an age-related form of macular degeneration. GA damages the macula – central part of eye – which causes vision loss.

New research demonstrates that females are more prone to AMD due to an age-related decrease in DHA 22:6, leading several experts to discuss its implications and treatment.

Aflibercept

Anti-VEGF agent Aflibercept reduces blood vessel growth that forms between the outer layer (sclera) and retina, in the eyeball’s choroid or pigmented layer – known as the choroid). Studies have demonstrated its efficacy at improving visual acuity for those suffering from age-related macular degeneration neovascularization as well as other eye conditions like diabetic macular oedema or choroidal vein occlusion; its side effects typically involve mild to moderate effects such as conjunctival haemorrhage, eye pain, increased intraocular pressure or even cataracts.

Submissions made in support of this claim asserted that Aflibercept 8 mg offered greater therapeutic benefit with an extended injection interval and equivalent safety versus its current 2 mg dosage in eyes with nAMD. These claims were supported by data from both VIEW-1 and VIEW-2 trials which assessed efficacy using ranibizumab 0.5 mg monthly dosing, Aflibercept 2 mg every eight weeks dosing and Aflibercept 8 mg every eight weeks following three initial monthly injections.

DRCR Protocol W trial results also showed that prophylactic anti-VEGF treatment with Aflibercept reduced vision-impairing complications by four years compared with sham therapy; however, its results were only modest; PBAC noted that costs estimates may depend heavily on projected uptake rates.

Avacincaptad Pegol

Avacincaptad Pegol, recently approved by the FDA for treating geographic atrophy associated with age-related macular degeneration (AMD), is an intravitreal injection which works by blocking complement C5. This inhibiting of complement C5 is thought to play an integral part in scarring and vision loss associated with GA.

A phase 2/3 clinical trial using Avacincaptad Pegol was found to significantly slow the growth of GA lesions when compared with a sham treatment, using slope measurements using fundus autofluorescence fundus autofluorescence fundus measurements and slope of square root transformed lesion area measurements as indicators of efficacy. It’s administered monthly via intravitreal injection.

Iveric Bio has developed a complement C5 inhibitor drug, administered once monthly through injection into the eye. Studies conducted have demonstrated its promise in slowing progression of GA among people with advanced dry AMD, as well as decreasing risks of choroidal neovascularization or wet AMD in advanced dry AMD patients. Furthermore, this is the first drug shown to slow its progression – it marks an historic first!

Susvimo

After seeing how successful anti-VEGF injections were at treating wet AMD, researchers looked to reduce patients’ treatment burden. While monthly injections are effective and convenient, they require frequent doctor’s office trips for administering ranibizumab. Thus, researchers began developing drug-eluting implants that deliver ranibizumab continuously such as Susvimo, which recently gained FDA approval to use in treating wet AMD. It consists of an ocular implant which releases 100mg/ml ranibizumab into each eye over six months for wet AMD treatment.

This drug-eluting implant for age-related macular degeneration was the first drug-eluting implant ever available on the market and received approval based on primary analysis from phase 3 Archway study. Results found it as effective as monthly anti-VEGF injections but came with some drawbacks such as three times higher risk of endophthalmitis than regular injections.

Genentech’s Susvimo implant can be placed into your eye during a single outpatient procedure and replenished every six months by an ophthalmologist. Clinical studies have demonstrated its ability to reduce vision loss among wet AMD patients while it also works well against diabetic macular edema. Multiple phase III studies are being conducted by Genentech involving Susvimo, including Portal, Pagoda Pavilion Velodrome studies.

Brolucizumab

Beovu contains brolucizumab, which was designed to block vascular endothelial growth factor (VEGF). VEGF is an unfavorable protein that causes new blood vessels to form within the eye and leak fluid into the retina, damaging central vision and leading to wet age-related macular degeneration or wet AMD. Beovu can also treat diabetic macular edema, proliferative diabetic retinopathy and retinal vein occlusion; administration via intravitreal injection is available from specialist eye clinics.

Studies conducted on Beovu have demonstrated its efficacy at improving best-corrected visual acuity (BCVA) and decreasing fluid accumulation associated with wet AMD, with lower risks for intraocular inflammation compared with other anti-VEGF agents. If approved by the FDA, Novartis plans on launching it by October.

New data from the HAWK and HARRIER phase III trials of brolucizumab (RTH258) 6 mg demonstrated its ability to significantly decrease macular fluid, in comparison with aflibercept, for patients suffering from wet AMD. This finding is significant given that retinal fluid serves as a key indicator of disease activity in wet AMD as well as diabetic macular edema.

Ranibizumab

Ranibizumab, an anti-vascular endothelial growth factor (VEGF) drug, has shown great promise for treating patients suffering from wet age-related macular degeneration. It can significantly slow progression and vision loss progression. Furthermore, focal photocoagulation combined with ranibizumab treatment has proved highly successful at improving visual acuity after laser therapy treatment; recently at uOttawa Health Sciences Centre in Canada they found combined treatments improve visual acuity after laser therapy; they recently published these results in Retina journal paper entitled “Ranibizumab plus photocoagulation for Macular Edema from Central Retinal Vein Occlusion”.

Clinical trials have demonstrated that 0.5 mg of ranibizumab can effectively decrease macular oedema in patients with CRVO. The primary endpoint was measuring how many patients gained fifteen letters or more on an ETDRS chart; additional analyses including functional and anatomic assessments favoured ranibizumab arms as well. Safety analysis was consistent with similar large studies of ranibizumab.

Retinal vein occlusion (RVO) is a disease of retinal veins which causes fluid leakage from capillaries draining into an obstructed vein, leading to buildups of fluid and thickness in the macula resulting in macular oedema. RVO may be caused by blood clots or other damage to retinal veins; vitrectomy and membrane stripping procedures are available to treat macular oedema due to RVO; however these procedures can be risky and painful procedures that should be used sparingly as treatments may pose risks or be painful procedures themselves.

Levodopa

Levodopa remains the gold standard PD treatment, yet over time its effectiveness becomes less reliable due to changes in the basal ganglia. These changes include reduced responsiveness from dopaminergic neurons as well as non-dopaminergic neurons linked to them, as well as their connections being broken off. Mucuna pruriens capsules containing 15% levodopa can be used as an additional therapy in order to extend its benefits; however it can cause hallucinations, delirium as well as increasing blood levels of catecholamines that could false-positive result for pheochromocytoma; trigger bronchospasm or increase intraocular pressure.

Syfovre

Pegcetacoplan (Syfovre) showed significant reductions in lesion growth during three pivotal studies: FILLY, DERBY and OAKS. Its complement inhibitor binds directly to components C3b to suppress excessive complement activation associated with GA. Pegcetacoplan was already approved by FDA as a subcutaneous infusion formulation under its brand name Empaveli for paroxysmal nocturnal hemoglobinuria patients.

Syfovre should be taken on a monthly or every-other-month basis. Apellis Pharmaceuticals of Waltham, Mass. has reviewed data from its clinical trials and found no association between Syfovre and instances of retinal vasculitis reported to the American Society of Retina Specialists as well as specific lots of medication.

Geographic atrophy is an irreversible condition resulting from atrophic lesions forming on the retina, harming vital retinal cells essential to vision. It differs from neovascular macular degeneration (wet AMD), where new blood vessels form on the macula leading to vision loss – this latter form being one of the primary causes of irreversible blindness among people over 50 years of age. Syfovre offers breakthrough treatment that could dramatically change lives for millions with advanced AMD.