Update AMD: First drug approved for the treatment of geographic atrophy

Over 5 million people globally suffer geographic atrophy linked to age-related macular degeneration. A new intravitreal drug was approved for its treatment.

World Sight Day 2023

12 October is World Sight Day, which raises awareness about visual impairment and blindness. According to the WHO, at least one billion people worldwide have a visual impairment at close and/or far range.

Hardly any treatment options for geographical atrophy 

Geographic atrophy is characterised by progressive and irreversible loss of the choriocapillaris, retinal pigment epithelium, and photoreceptors. So far, there are hardly any treatment options for this advanced stage of AMD. One year ago, we learned about an experimental method that offered hope for patients with geographic atrophy. This involved a patch of induced pluripotent stem cells (iPS) developed by a research team from the Ocular and Stem Cell Translational Research Section in collaboration with FUJIFILM Cellular Dynamics Inc. and Opsis Therapeutics. However, this method has not yet received regulatory approval.2

Significant slowing of disease progression in GA with avacincaptad pegol

Izervay is the only approved treatment for geographic atrophy with a statistically significant reduction in progression rate 12 months after starting treatment. On 4 August 2023, the US Food and Drug Administration (FDA) approved Izervay (avacincaptad pegol intravitreal solution) to biopharmaceutical company Iveric Bio for the treatment of geographic atrophy. Iveric Bio is part of Astellas Company and focuses on the discovery and development of therapies for retinal diseases. The approval of Izervay was based on the positive results of the two phase III trials. With Izervay, there was a slowing of photoreceptor loss and disease progression as early as six months.3

In the two phase III trials, GATHER1 (doi: 10.1038/s41433-023-02497) and GATHER2, patients received 2mg and 4mg of Izervay intravitreally. Patients were followed up for a total of 12 months. The results were compared with the control group (SHAM treatment). Analysis of the data showed a statistically significant reduction in the rate of progression of geographic atrophy compared to the control group. Reduction in disease progression was observed after only 6 months, which amounted to 35% after 1 year.

The reduction in mean GA growth rate over 12 months in the phase II/III GATHER1 trial was 27.4% (p = 0.0072) for the 2 mg cohort and 27.8% (p = 0.0051) for the 4 mg cohort - compared to the control group. In the large-scale phase III GATHER2 trial, patients received only 2 mg cohort Izervay, which was considered optimal.3,4

Marked vision loss in non-foveal GA could be reduced with Izervay

In both the GATHER1 and GATHER2 studies, a 56% reduction in marked vision loss was observed. This is similar to the reduction of sustained vision loss of ≥ 50 letters over two consecutive visits. However, it is important to note that only study patients with non-foveal GA were included in the two studies.5

A convincing safety profile

Treatment with Izervay was associated with a very good safety profile. The most commonly reported adverse events at 1 year had been hyposphagmia (subconjunctival hemorrhage) in 13%, increased intraocular pressure in 9% and blurred vision in 8% of patients. Izervay is contraindicated in patients with ocular or periocular infections or in patients with active intraocular inflammation.3

What other complement inhibitors are available in GA?

Izervay is a complement C5 inhibitor whose mechanism of action is to counteract retinal cell death. In addition to Izervay, other complement inhibitors have been studied in GA in recent years. These include pegcetacoplan and lampalizumab. Both were also administered intravitreally and compared with sham treatments. In a total of three studies, no significant improvement in visual acuity was observed for lampalizumab. There was also no significant effect on the rate of progression of GA lesions.

Pegcetacoplan also did not lead to a significant improvement in visual acuity, but there was a reduction in the rate of progression of GA lesions in a total of three studies. The reduction in the rate of progression of GA lesions was equivalent to 19.2% and 14.8%, respectively, compared with placebo treatment. In extrafoveal GA, the benefit of pegcetacoplan was greater.6 To date, Izervay is the only approved complement inhibitor for GA.

  1. Geographic Atrophy.
  2. National Institutes of Health. News Release. 31 August 2022. "First U.S. patient receives autologous stem cell therapy to treat dry AMD".
  3. https://www.astellas.com/en/news/28281
  4. Jaffe GJ. et al. (2021). C5 Inhibitor Avacincaptad Pegol for Geographic Atrophy Due to Age-Related Macular Degeneration: A Randomized Pivotal Phase 2/3 Trial. Ophthalmology. 2021 Apr;128(4):576-586. 
  5. https://www.optometrytimes.com/view/recently-approved-izervay-offers-new-treatment-for-patients-with-geographic-atrophy
  6. Tzoumas N. et al. (2023). Complement inhibitors for age-related macular degeneration. Cochrane Database Syst Rev. 2023 Jun 14;6(6):CD009300.