Current treatments for dry age-related macular degeneration lack any efficacy; the disease causes painless loss of central vision beginning with blurry or discolored spots that fade with bright lighting conditions. Your eye care professional can verify if there has been an alteration by having you view an Amsler grid to check for changes.

Risuteganib

Risuteganib is a small synthetic peptide designed to regulate specific integrin functions involved in dry age-related macular degeneration’s pathogenesis and potentially reverse vision loss from this prevalent eye condition. By blocking key signaling cascades that result in photoreceptor degeneration and retinal pigment epithelial (RPE) degeneration as well as inflammation, degradation of mitochondrial energy production systems, as well as enhanced cell viability, axonal growth, and preservation of remaining retinal pigment epithels; currently it is being clinically evaluated as potential treatment options.

Researchers recently reported that Risuteganib significantly enhanced best-corrected visual acuity for intermediate nonexudative dry AMD patients in a Phase 2 randomized, double-masked, placebo controlled study. Patients received either one mg intravitreal injections of Risuteganib or an inactive control injection at baseline in each eye and this particular trial excluded patients who also suffered from concurrent vision-altering or macula-obscuring conditions.

The study’s primary endpoint was the proportion of subjects who gained eight or more letters of BCVA compared to sham group, an important clinical benchmark that represents meaningful progress in dry AMD progression. A substantial number of risuteganib-treated patients improved their vision by over 10 letters; one patient gained 15! Furthermore, two independent reading centers conducted post-hoc analyses which indicated higher-order OCT features including outer retinal thickness and photoreceptor volume increase as well as smaller ellipsoid zone defect areas as well as reduced geographic atrophy were all linked with greater BCVA responses when administered risuteganib.

Shanghai AffaMed will launch China Phase III trials of risuteganib, currently known in Europe as AM011, starting in 2021. AffaMed recently acquired greater China rights for this candidate from South Korean Hanmi Pharma.

Syfovre

Syfovre, an intravitreal injection approved by the FDA to treat geographic atrophy (GA), an advanced form of age-related macular degeneration that results in vision loss over time due to retinal cell death, is now approved for use. Targeting complement pathway can slow lesion growth.

The drug works by blocking complement from activating C3b protein – which triggers retinal lesions in GA – through FDA trials, showing a 36% decrease in lesion growth over 18-24 month period. Patients receiving injections monthly or every other month in an outpatient setting should report any side effects to their physician immediately.

Syfovre was approved by the Food and Drug Administration on February 17 to treat GA secondary to age-related macular degeneration, with its first commercial launch anticipated for mid-2023. While it’s the first FDA-approved treatment for this advanced stage of AMD, competitors such as Iveric Bio Inc’s once monthly Izervay intravitreal injection also gained approval by August.

Both Izervay and Syfovre belong to a class of medications known as coagulation factor inhibitors, which work by decreasing blood clots in the eye, thus decreasing macular bleeding risk and retinal tear or detachment risk, while simultaneously decreasing inflammation associated with GA progression.

Syfovre was approved by the FDA as the first treatment for GA, yet has been plagued with numerous adverse events since. Common side effects include ocular discomfort, neovascular age-related macular degeneration, vitreous floaters and conjunctival hemorrhage; therefore it is imperative that doctors closely monitor patients to detect these potential side effects. The FDA requires doctors to monitor patients closely in case any such issues arise.

ASRS issued a warning to physicians about the potential risk for intraocular inflammation associated with use of Syfovre, the recently approved geographic atrophy drug. ASRS’s Research and Safety in Therapeutics Committee received six cases of occlusive retinal vasculitis following Syfovre administration between January 1 and April 1, 2023 and reported them directly to ASRS for review.

Pegcetacoplan

Apellis Pharmaceuticals’ C3 inhibitor pegcetacoplan (APL-2) was recently approved by the FDA to treat geographic atrophy associated with dry age-related macular degeneration. Syfovre was shown to significantly reduce GA lesions growth during clinical trials. Apellis anticipates its drug will become standard treatment for this disease.

Long term studies conducted by DERBY and OAKS demonstrated the drug’s efficacy in mitigating GA’s progression, as evidenced by monthly and every-other-month injections of pegcetacoplan reduced lesion progression compared to sham treatments, and had a safety profile consistent with short term trials.

Pegcetacoplan was found to reduce lesion progression rates by 36% during both trials; furthermore, its costs were estimated as being less expensive than both eculizumab and ravulizumab (although exact figures remain confidential).

Modern Retina interviewed key opinion leaders (KOLs) to assess possible treatment for GA, such as oral therapies and antibodies, that might offer significant advantages over existing options. According to these interviewees, these therapies may require multiple visits which could become cumbersome to patients while oral therapies might not be suitable for severe or advanced GA cases.

Even with limited treatment options available to them for treating GA, physicians remain optimistic about its future. Surveyed ophthalmologists anticipated prescribing pegcetacoplan to 39% of their GA patients prior to its approval and are hopeful about the forthcoming release of GARLAND data, an observational study which will analyze real-world outcomes among GA patients.

At present, GA treatment primarily consists of taking dietary supplements with frequent eye injections to slow its progression; these medications do not provide functional benefits or cures; many patients avoid taking AREDS 2 supplements due to fear of having eye injections and potential side effects; more effective solutions such as pegcetacoplan and avacincaptad pegol could become available in the near future.

Luminate

Luminate, developed by Allegro Ophthalmics, is the newest treatment to address dry age-related macular degeneration (AMD), an increasingly prevalent and severe form of vision loss. Risuteganib (Luminate, Allegro Ophthalmics) fills an apparent market gap when it comes to treating AMD and other eye conditions; its small molecule inhibits oxidative stress that damages photoreceptors and retinal pigment epithelial cells and has shown to significantly improve visual acuity among patients with mild to moderate non-exudative AMD cases.

Luminate is currently being evaluated in a phase III clinical trial, known as LUMINATE, to assess efficacy and safety. The trial will enroll 40 subjects with intermediate non-exudative AMD who require treatment, who will be randomly allocated either an intravitreal injection of Luminate or an inactive injection as per protocol (1.7:1).