Syfovre

Syfovre is the first and only FDA-approved treatment for geographic atrophy (GA). GA is the advanced form of dry age-related macular degeneration (AMD) and is a leading cause of blindness, affecting over 1 million people in the United States and five million worldwide. GA is the most advanced stage of dry AMD, causing progressive retinal deterioration that leads to expanding blind spots and permanent vision loss. Syfovre (pegcetacoplan) is given as a prescription eye injection by a retina specialist, once every 25 to 60 days.

GA is caused in part by an overactive complement immune response in the eye, which damages and destroys retinal cells called photoreceptors and the retinal pigment epithelium (RPE). Once these cells are lost, the damage cannot be reversed. Syfovre works by blocking a protein called C3, a key activator in the complement immune cascade, to help regulate the overactive immune system and slow GA lesion growth.

Syfovre received FDA approval on February 17, 2023.

Syfovre is administered in-office by a retina specialist as an injection into the vitreous, which is the gel-like interior of the affected eye. Your doctor may take a scan and numb the eye before the injection.

• Although you may feel pressure during the injection, it should not be painful.
• After the injection, your doctor may monitor your eye pressure and overall eye health before you leave.
• Vision changes or discomfort may occur temporarily after the injection. Do not drive or operate machinery until your vision fully recovers.
• Plan for some rest time after each appointment.

Do not receive Syfovre if you have an infection or active swelling in or around your eye that may include pain and redness, or are allergic to pegcetacoplan or any ingredients in Syfovre. Syfovre can cause serious allergic reactions such as trouble breathing; tongue, face, lips, or mouth swelling; rashes; and hives.

Before receiving Syfovre, tell your healthcare provider about all your medical conditions, including if you have:

• Have a history of seeing flashes of light or small specks floating in your vision, and notice a sudden increase in the size and number of these specks
• Have high pressure in the eye or glaucoma
• Have allergies to pegcetacoplan, Syfovre, or any inactive ingredients in Syfovre
• Are or think you are pregnant, breastfeeding, or planning to have a baby, ask your doctor for advice before taking this medicine

Pregnancy

It is not known if Syfovre will harm an unborn baby. If you are a woman with childbearing potential, use effective contraception methods to prevent pregnancy during treatment with Syfovre eye injection and for 40 days after the last dose of Syfovre. For women planning to become pregnant, the use of Syfovre may be considered following an assessment of the risks and benefits.

Breastfeeding

It is not known if pegcetacoplan passes into breastmilk. Talk to your doctor about the best way to feed your baby if you are breastfeeding.

Serious Side Effects

Syfovre can cause serious side effects, such as:

• Eye Infections (endophthalmitis) or separation of layers of the retina (retinal detachment) Any eye injection, including Syfovre, carries risks of serious infection (endophthalmitis) or retinal detachment. Your doctor uses sterile technique to minimize this infection risk. Call your healthcare provider right away if you have eye redness, light sensitivity, eye pain, or any change in vision, including blurred, wavy/distorted vision, specks floating in your vision, or flashing lights.
• Severe inflammation or blockage of blood vessels in the retina, which may result in severe vision loss. Call your healthcare provider right away if you have eye redness, light sensitivity, eye pain, or any change in vision, including blurred, wavy/distorted vision, or flashing lights.
• Risk of developing wet AMD. You should be monitored for signs of wet AMD and you should report if you have any change in vision, including blurred, wavy/distorted vision, black spots, or loss of central vision to your healthcare provider.
• Episodes of eye inflammation. You should report any symptoms, including eye redness, light sensitivity, eye pain, small specks floating in your vision, or any changes in vision to your healthcare provider.
• Increase in eye pressure within minutes of the injection. Your healthcare provider will monitor this after each injection.

Common Side Effects

The most common side effects of Syfovre are:

• Eye discomfort
• Wet (neovascular) age-related macular degeneration
• Floaters (small specks in your vision)
• Conjunctival hemorrhage (blood in the white of the eye).

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Dose of Syfovre for Geographic Atrophy (GA)

• Adults: 15 mg (0.1 mL of 150 mg/mL solution) by intravitreal injection to each affected eye, once every 25 to 60 days.
• Your retina specialist will determine the right injection interval based on your individual response to treatment, GA lesion progression rate, and overall eye health.

Syfovre (pegcetacoplan) is a complement inhibitor. It works by blocking a protein called C3, a key activator in the complement immune cascade. In patients with GA, an overactive complement system accelerates retinal cell death. By inhibiting C3, Syfovre helps regulate this overactive immune response and slows the growth of GA lesions.

Syfovre cannot cure GA or reverse damage that has already occurred. It is designed to slow the rate of disease progression, helping patients preserve remaining vision for longer.

Phase 3 Trials: OAKS and DERBY (24 Months)

Two large Phase 3 studies involving more than 1,200 patients, OAKS ( NCT03525613) and DERBY (NCT03525600), demonstrated that Syfovre significantly slowed GA lesion growth over 24 months compared to placebo (untreated) controls.

Results at 24 months:

• Monthly injections: slowed GA lesion growth by 18–22%
• Every-other-month injections: slowed GA lesion growth by 16–18%
• Both dosing schedules showed consistent, sustained benefits throughout the two years

While slowing disease progression helps patients preserve remaining vision longer, the trials did not show statistically significant improvements in reading speed at 24 months.

GALE Long-Term Extension Study (36 Months and 5 Years)

More than 80% of participants from OAKS and DERBY enrolled in the GALE long-term extension study, providing some of the most robust long-term data available for any GA therapy.

Key findings from GALE:

• At 36 months, Syfovre preserved visual function, making it the only approved GA treatment to demonstrate a visual function benefit at a prespecified endpoint.
• At 5 years, Syfovre delayed GA progression by approximately 1.5 years compared to the projected untreated disease course.

These long-term results support the sustained benefit of continued Syfovre treatment beyond the initial two-year phase.

After a Syfovre injection or eye exam, your vision may be temporarily impaired. Do not drive or operate machinery until your vision has fully recovered.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Syfovre (pegcetacoplan) has no known clinically significant interactions with other drugs, herbs, supplements, or foods. However, some systemic medications may affect eye health or treatment response.

Syfovre Insurance Billing: J Code J2781

HCPCS J Code: J2781

• Used for Medicare, Medicaid, and private insurance claims

Coverage varies by insurance plan. Syfovre is an FDA-approved treatment for geographic atrophy, which helps with insurance coverage. Contact your insurance provider or the manufacturer's patient support program at 1-833-866-3346 for assistance with coverage questions.

Syfovre is manufactured for Apellis Pharmaceuticals, Inc., 100 Fifth Avenue, Waltham, MA 02451.