Syfovre injection has been approved by the FDA as an intravitreal injection to treat an advanced form of dry age-related macular degeneration called geographic atrophy. It helps slow or prevent its progression, which could otherwise result in vision loss or blindness.

Syfovre demonstrated significant GA lesion growth reduction when compared with placebo treatment in both studies; its treatment effects increased over 24 months.

Overview of age-related macular degeneration

Age-Related Macular Degeneration (AMD) is a painless eye disease that slowly destroys sharp central vision required for reading, driving and recognising faces. An estimated one million Americans and five million worldwide have AMD; symptoms may vary from dimming or distortion of straight lines to total loss of central vision as light-sensing cells within the macula degrade over time, rendering retina inactive to light signals received. AMD is the leading cause of severe vision loss among people over 55; early symptoms can only be detected via dilated eye examination.

Dry and wet AMD are two forms of the same disease, distinguished by abnormal blood vessel growth beneath or near the retina that leak fluid and cause distortion of straight lines and blurry vision. Wet AMD usually progresses more quickly than its dry form; intravitreal injections of medication such as Lucentis or Avastin may help stop its advancement by blocking vascular endothelial growth factor which stimulates its abnormal vessel growth.

SYFOVRE was found to significantly slow the progression of geographic atrophy (GA) lesions during both of its clinical trials DERBY and OAKS, in comparison with placebo. C3, a component of the complement system that damages retinal pigment epithelial cells and photoreceptors when GA progresses, was inhibited by this drug.

However, Apellis Pharmaceuticals was concerned by an increase in neovascular (wet) macular degeneration among some users; this occurred among 12% of monthly dose recipients; 7% received every other month doses and 3% took placebos as treatment; however reevaluating clinical trials did not reveal any new safety issues.

Retina Health Institute can help those at risk for wet macular degeneration learn more by diagnosing their condition and creating a treatment plan to preserve vision. Contact us now to arrange an appointment!

Complement cascade

The complement system is an essential component of our natural immune defense against pathogens and harmful organisms, while providing host defense. However, when disease or injury disrupts its proper function, its consequences can become destructive. The complement cascade involves tightly regulated enzymatic reactions which activate C1q component to create C3b which in turn releases anaphylatoxins cleaved off into C5a anaphylatoxins that bind cell surface molecules and lead to an inflammatory response.

Syfovre inhibits complement cascade by blocking C1q component to stop formation of complexes that damage cells, including photoreceptors and retinal pigment epithelium (RPE), leading to macular edema in wet age-related macular degeneration. Syfovre is currently the only FDA-approved treatment for wet age-related macular degeneration.

An instrument called a lancet is used to draw small amounts of blood from fingers or arms of patients using needles called lancets, then collected into tubes or glass vials for testing of complement components such as C3 and C4. Once collected, these samples may cause mild pain or discomfort but ultimately tested for complement components C3 and C4.

Early signs of wet macular degeneration include macular edema, blurred vision and reduced contrast sensitivity; left untreated these symptoms can result in permanent vision loss. Syfovre offers a new treatment option which reduces macular edema by inhibiting complement cascade. It also helps stop build-up of drusen deposits that block light reaching retina; limited quantities are currently available through specialty distributors and pharmacies nationwide.

Intravitreal injections such as those used in administering SYFOVRE may increase your risk of endophthalmitis and retinal detachment, so proper aseptic technique is key to minimizing this risk. Patients should be instructed to report any symptoms immediately to their healthcare provider.

Geographic atrophy

Geographic Atrophy (GA) is an advanced stage of dry AMD that results in the growth of atrophic lesions that eventually cause irreversible vision loss. GA differs from wet or neovascular age-related macular degeneration (nAMD), in which new leaky blood vessels invade the macula to rapidly decrease vision. GA lesions initially start outside the center area known as fovea before eventually expanding and covering more central retinal area; GA is considered an ischemic disease as it results in decreased blood supply to choriocapillaris resulting in retinal pigment epithelial cell deaths which eventually leads to irreversible vision loss.

Studies conducted recently at the 2023 Association for Research in Vision and Ophthalmology Annual Meeting revealed that GA patients treated with pegcetacoplan saw less vision loss than those receiving sham injections. Pegcetacoplan works by inhibiting C3, an important protein involved in retinal pigment epithelial cell death caused by AMD/GA, thus helping preserve function by protecting these cells and slowing their progression of disease progression.

Researchers conducted a survey among 149 geographic atrophy patients from both the United States and Canada. They asked questions regarding their quality of life and impact of vision-related functioning on daily activities, and also interviewed 148 caregivers of these patients. Most lived with another person and stopped driving due to worsening vision; caregivers reported reduced work capacity as well as decrease in health-related quality of life.

Georgia Retina and Apellis Pharmaceuticals have joined forces to conduct clinical trials of their FDA-approved treatment, SYFOVRE. It is an intravitreal injection designed to slow geographic atrophy progression in advanced dry age-related macular degeneration patients; two Phase III clinical trials demonstrated statistically significant reduction in GA lesion growth rates; this treatment has proven safe and effective with most patients; common adverse reactions include eye discomfort, neovascular macular disease symptoms such as vitreous floaters or conjunctival hemorrhages.

Pegcetacoplan

Pegcetacoplan, a C3 complement inhibitor approved by the FDA to halt geographic atrophy (GA) progression in dry age-related macular degeneration, was recently shown to reduce its progression via a phase III study and be effective in slowing GA lesion growth while improving vision; additionally it had an acceptable safety profile.

GA is a progressive form of macular degeneration caused by retinal pigment epithelial cell death and photoreceptor death as a result of abnormalities in complement cascade regulation in the retina, eventually leading to formation of fibrovascular tissue that eventually invades and obscures fovea, the central region containing cone photoreceptors which provide for sharpest vision. GA leads to loss of central and color vision as well as gradually reduced independence and quality of life over time.

Though the exact causes of GA remain elusive, several studies have linked its development with abnormal complement activation and activation in retinal pigment epithelium cells. Both OAKS and DERBY trials demonstrated that administering C3 complement inhibitor pegcetacoplan significantly slowed progression of GA in both exudative and nonexudative forms when compared to receiving placebo injections.

Trials showed that SYFOVRE was generally safe and well tolerated; however, some patients experienced serious adverse events, including ocular hypotension, increased intraocular pressure increases immediately post injection and inflammation. Anti-inflammatory medication such as Acyclovir or Corticosteroids are available to manage inflammation side effects effectively.

Intravitreal injections may lead to endophthalmitis and retinal detachments, making the use of aseptic injection technique essential when administering SYFOVRE to limit their risks and ensure its safe administration. It’s also important for patients to report any symptoms of endophthalmitis or retinal detachment immediately so they can be promptly monitored and managed accordingly.