Avacincaptad pegol well-tolerated, slows geographic atrophy at 12 months in dry AMD
Click Here to Manage Email Alerts
Key takeaways:
- Geographic atrophy area growth was significantly slower in patients treated with avacincaptad pegol 2 mg vs. sham.
- Adverse events occurred in 49% of the avacincaptad pegol group and 37% of the sham group.
The complement component 5 inhibitor avacincaptad pegol may have potential as a treatment to reduce geographic atrophy lesion growth and slow progression of disease, according to a study published in The Lancet.
“The results of GATHER2 showed that monthly C5 inhibition with avacincaptad pegol 2 mg showed slower geographic atrophy growth compared with sham treatment and was well-tolerated over 12 months of treatment,” Arshad M. Khanani, MD, director of clinical research at Sierra Eye Associates and clinical associate professor at University of Nevada Reno School of Medicine, and colleagues wrote.
Between June 2020 and July 2021, researchers enrolled 448 patients aged 50 years or older with non-centerpoint-involving geographic atrophy, who were randomly assigned to receive avacincaptad pegol 2 mg, administered as a monthly 100 L intravitreal injection, or sham. The groups were fairly evenly distributed, with 225 individuals (68% women) in the avacincaptad group and 223 in the sham group (70% women).
Researchers performed monthly full ophthalmological examinations and OCT from the start of the study through month 12, as well as assessments of best corrected visual acuity and IOP.
According to results, the mean rate of square-root-transformed geographic atrophy area growth in the avacincaptad pegol group was 0.336 mm per year compared with 0.033 mm per year in the sham group.
Treatment-related adverse events were reported in 49% of the avacincaptad pegol group and 37% of the sham group, with the most common being conjunctival hemorrhage and hyperemia, punctate keratitis, increased IOP, macular neovascularization, dry eye, eye pain, vitreous detachment and cataract. None of the patients experienced endophthalmitis, intraocular inflammation or ischemic optic neuropathy events throughout the study period.
“Although monthly injections can be a substantial burden to both patients and clinicians, the results of this study show that there is a treatment that can be used to slow the progression of the disease and the associated effect on the patient’s vision,” Khanani and colleagues wrote.
Perspective
Back to Top
Until very recently, there has been a paucity of management options for our patients with geographic atrophy, and this phase 3 randomized clinical trial of avacincaptad pegol lends hope.
However, there is much we do not know. How many months or years of treatment are needed until a vision benefit is measurable? What is the effectiveness in patients who already have geographic atrophy extending into the central fovea? Are there uncommon but vision-threatening side effects that may not have been observed in the relatively small sample size and limited study duration of the GATHER 2 study?
Concerns stemming from recent post-market reports of rare occlusive retinal vasculitis associated with the administration of intravitreal pegcetacoplan, a complement 3 inhibitor approved by the FDA in 2021 for treatment of geographic atrophy, are an excellent reminder that vigilance to post-market experience will be imperative with avacincaptad pegol. Many questions will need answers before we know if this study leads to a true paradigm shift in the management of these patients.
Well-informed patients with geographic atrophy will certainly be asking their optometrists about complement inhibitors, including avacincaptad pegol. However, conversations weighing indefinite and costly monthly injections without a method of determining effectiveness at an individual level — with limited information on long-term safety and effectiveness and an increased risk for choroidal neovascularization — must be nuanced.
Collapse
Read more about
Click Here to Manage Email Alerts