Iveric Bio, an Astellas Pharma Inc. company, announced 2-year data from the phase 3 GATHER2 clinical trial assessing IZERVAY (avacincaptad pegol intravitreal solution) 2 mg for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
The results were presented during the American Academy of Ophthalmology (AAO) annual meeting.
Refresh me on IZERVAY.
First things first: the FDA granted IZERVAY (pronounced EYE-ZER-VEY) approval in August 2023 as the first and only GA treatment with a statistically significant reduction in the rate of GA progression at the 12-month primary endpoint.
Developed initially under the name ACP/Zimura, IZERVAY is a complement C5 inhibitor formulated to slow GA progression.
Per the prescribing information, a 2 mg (0.1 mL of 20 mg/mL solution) is to be administered via intravitreal injection to each affected eye once a month for up to 12 months.
Isn’t there clinical data already out on it?
Yes, there is!
See here for details on the topline 24-month data from the GATHER2 trial, and here for coverage on the 12-month data from the previous GATHER1 (NCT02686658) and GATHER2 (NCT04435366) phase 3 trials
Gotcha. Remind me of the GATHER2 trial results so far.
In year 2 of the GATHER2 trial (n = 448), IZERVAY-treated patients were re-randomized to be administered IZERVAY on a monthly (n = 96) or every-other month ([EOM], n = 96) basis.
Sham-treated patients (n = 203) from year 1 continued to be administered sham in year 2.
And the goal: to determine whether (after re-randomization), IZERVAY continued to slow GA growth rate for monthly treated vs sham-treated patients.
And the newly-released data?
Presented by Arshad M. Khanani, MD, MA, FASRS, director of Clinical Research at Sierra Eye Associates, Reno, Nevada, the results demonstrated that IZERVAY continued to reduce the rate of GA lesion growth for both monthly and EOM dosing when compared to sham through 2 years of treatment.
How early was this benefit observed?
Per the data, as early as 6 months—and continued to increase over time through 2 years (and more than doubled over 2 years vs year 1).
Talk numbers.
- For Izervay dosed monthly (through 2 years)
- 14% statistically significant year-over-year reduction in the mean rate of GA growth at 2 years from baseline vs sham (p=0.0165)
Note: this was the primary objective for year 2
- For Izervay dosed EOM, after a year of monthly dosing
- 19% reduction in the mean GA growth rate at 2 years vs sham (nominal p-value=0.0015).
How was the tolerance?
The company reported IZERVAY to be well-tolerated over 2 years, “with one case each of non-serious intraocular inflammation (IOI) and culture-positive endophthalmitis.”Of note, there were no cases of ischemic neuropathy or retinal vasculitis.
What about CNV?
Over the 2-year period, there was only a slight increased incidence of choroidal neovascularization (CNV) observed for IZERVAY pooled vs. sham data. In year 2, CNV incidence was similar for IZERVAY EOM vs. sham.
Give me the takeaway.
While IZERVAY received FDA approval in August 2023 and is currently under a review by the European Medicines Agency (EMA), the company is looking to submit this data back to the FDA by Q1 2024.
The goal: Have the label updated to include EOM dosing and Year 2 data.
The American Academy of Ophthalmology annual meeting is being held Nov. 3-6 2023, in San Francisco, California.