Avacincaptad Pegol

Avacincaptad pegol (Izervay) injection is a treatment for geographic atrophy (GA), which is due to age-related macular degeneration (AMD). Avacincaptad pegol injection helps to slow down the progression of geographic atrophy so your vision does not deteriorate as rapidly, allowing you to maintain better vision for a longer time. Geographic atrophy can lead to irreversible vision loss.

Avacincaptad pegol is given as an intravitreal injection (injection into the eye) every 28 days.

Avacincaptad pegol brand name is Izervay made by Astellas Pharma Inc.

Avacincaptad pegol FDA approval indication is for geographic atrophy (GA) secondary to age-related macular degeneration (AMD) under the brand name Izervay. The FDA approval was granted on August 4, 2023.

Geographic atrophy is an advanced form of dry age-related macular degeneration (AMD) that can lead to progressive and irreversible vision loss. Geographic atrophy lesions start as small damaged areas that gradually grow and can spread to the retina's center, which is needed for sharp vision. The damage is caused by an overactive part of the immune response called the complement system.

Avacincaptad pegol helps slow the progression of GA by targeting an overactive immune system response that has a damaging effect on the retinal cells.

Avacincaptad pegol mechanism of action is as a complement inhibitor, it inhibits C5, a key protein in the complement cascade—a part of the immune system that when overactive, damages retinal cells and speeds up GA progression.

By blocking C5, avacincaptad pegol injection reduces immune system overactivity and helps maintain better vision for a longer time by:

• Reducing future damage to retinal cells
• Slowing the spread of GA lesions
• Delaying loss of vision.

Avacincaptad pegol clinical trial: GATHER1 & GATHER2 trials

Avacincaptad pegol treatment was evaluated in two clinical trials GATHER1 (NCT02686658) and GATHER2 (NCT04435366), which followed over 18- and 12-month studies 24 months to measure its effectiveness in slowing geographic atrophy (GA) progression.

Key Results:

GATHER1 Trial (177 Participants):

• Monthly avacincaptad pegol injections GA lesion growth 1.22 mm²/year.

• Monthly placebo injections GA lesion growth was 1.89 mm²/year.

• Difference GA lesion growth was 35%* between Avacincaptad pegol and placebo.

GATHER2 Trial (447 Participants):

• Monthly avacincaptad pegol injections GA lesion growth 1.75 mm²/year.

• Monthly placebo injections GA lesion growth was 2.12 mm²/year.

• Difference GA lesion growth was 18%* between Avacincaptad pegol and placebo 35%

Study Design:

• GATHER1 trial had 67 patients using avacincaptad pego injections 110 received placebo injection
• GATHER2 trial had 225 patients using avacincaptad pego injections 222 received placebo injection
• Participants ranged in age from 51 to 97 years (average age 77 years).

*% difference is calculated by 100*(difference)/(least squares mean from placebo)

Avacincaptad pegol injections are given by a qualified physician as intravitreal injections, which means the medication is injected directly into the vitreous humor in the eye. Your doctor will monitor the pressure inside your eye before and after the injection.

Before use, allow Izervay to reach room temperature, 20⁰C to 25⁰C (68⁰F to 77⁰F).

Avacincaptad pegol intravitreal solution 20 mg/mL in a single-dose vial

• Endophthalmitis and retinal detachments
• Neovascular AMD
• Increase in intraocular pressure (IOP).

You should not use avacincaptad pegol injection if you have ocular or periocular infections or active intraocular inflammation.

Common avacincaptad pegol side effects

The most common avacincaptad pegol side effects include:

• Increased pressure inside the eye 9%,
• Blurred vision (visual impairment, vision blurred, visual acuity reduced, visual acuity reduced transiently) 8%,
• Bleeding in the white part of the eye (conjunctival hemorrhage) 13%,
• Choroidal neovascularization (CNV) 7%
• Eye pain 4%
• Vitreous floaters 2%
• Blepharitis (inflammation of the eyelids) 2%

Serious avacincaptad pegol side effects

Do not use this medicine if you are allergic to the active ingredient avacincaptad pegol or any of its other ingredients.

Other serious Izervay side effects include:

• signs of eye infection - swelling, severe discomfort, crusting or drainage;
• severe eye redness or pain;
• eyes being more sensitive to light;
• blurred or cloudy vision; or
• changes in your vision, seeing flashes of light.

Also, see the Warnings and Precautions section

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 FDA at 1-800-FDA-1088.

Usual Adult Izervay Dose for Macular Degeneration:

Recommended dose: 2 mg intravitreal injection given once monthly (28 ± 7 days)

General dose information:

• Before the intravitreal injection, check the intraocular pressure (IOP).
• If necessary, ocular hypotensive medicine can be administered to reduce IOP.

What happens if I miss a dose?

Make an appointment or call your qualified physician as soon as you realize you have missed your dose to organize a new appointment,

You may experience temporary visual disturbances and blurring, after having your injection and the associated eye examinations. Avoid driving or using machinery until the visual function has recovered sufficiently.

Other drugs may interact with this medicine. Tell your doctor about all the other medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal products.

Review the Avacincaptad Pegol Package Insert (Izervay brand) Prescribing Information for more detailed information about this medicine. Discuss any medical questions with your doctor or other health care provider. This is not all the information you need about this medicine for safe and effective use, and it does not take the place of talking to your doctor about your treatment.

• Store in the refrigerator between 2°C to 8°C (36°F to 46°F).
• Do not freeze. Do not shake.
• Keep the vial in the original carton to protect it from light.

Before use

• Prior to use, the unopened glass vial may be kept at room temperature, 20°C to 25°C (68°F to 77°F), for up to 24 hours.
• Ensure that the injection is given immediately after preparation of the dose.

Active ingredient: avacincaptad pegol (oligonucleotide basis),

Izervay Inactive ingredients: 0.198 mg dibasic sodium phosphate heptahydrate, 0.0256 mg monobasic sodium phosphate monohydrate, and 0.83 mg sodium chloride. It is formulated in Water for Injection, with a target pH of 7.3. This medicine does not contain an anti-microbial preservative.