Astellas Pharma Inc. recently reported the first data from an open-label extension (OLE) trial of IZERVAY (avacincaptad pegol intravitreal [IVT] solution), its FDA-approved treatment for geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
New data?! Wowza … but let’s start with an IZERVAY refresher.
First approved in 2023, the prescription-based C5 inhibitor made history in becoming the first (and still only) GA treatment with a statistically significant reduction in the rate of GA progression at the 12-month primary endpoint in clinical trials.
Its dosing schedule: 2 mg (0.1 mL of 20 mg/mL solution) is to be administered by intravitreal injection to each affected eye once a month (EM) or every other month (EOM).
Is there a limit to this dosing?
Funny you should ask … prior to the FDA greenlighting an expanded U.S. prescribing information (PI) of the therapeutic earlier this year, IZERVAY’s dosing was limited to up to 12 months.
- With the updated labeling: There is no limitation on the duration of its dosing (effectively enabling longer-term administration for patients).
That’s quite the difference … now what should we know about this new research?
For starters, it’s based on an 18-month OLE trial of the phase 3 GATHER2 study (NCT04435366).
If that study sounds familiar: Its original 12-month clinical findings were included in IZERVAY’s original new drug application (NDA) submission to the FDA—along with data from the phase 3 GATHER1 trial—while its 24-month data was key to securing the therapeutic’s updated labeling.
Talk about this OLE trial.
The setup: Participants who completed the GATHER2 study (to note: 448 patients were enrolled) switched from receiving:
- Group 1: IZERVAY EM or EOM to IZERVAY EM
- Group 2: Sham to IZERVAY EM
As for the outcome measures: The mean change in GA lesion growth was evaluated from Month 24 (the end of the GATHER2 study) to 3.5 years.
Now to the data.
Monthly treatment with IZERVAY continued to reduce GA lesion growth for up to 3.5 years—and earlier intervention resulted in greater protection of the retinal tissue area.
Get more specific on this lesion growth reduction.
To be exact: The mean change in GA lesion growth area was reduced by:
- 40.5% from month 24 (mm2/year) compared to predicted sham in patients who switched from IZERVAY EM/EOM to IZERVAY EM at 3.5 years (p<0.001)
- 37% from month 24 (mm2/year) compared to projected sham in the IZERVAY EM group who previously received sham (p<0.001)
Can we get more specific about the earlier intervention you mentioned?
Absolutely. Per Astellas, earlier IZERVAY intervention “consistently resulted in greater protection of retinal tissue area.”
The numbers:
- 2.92 mm2 in the group that switched from IZERVAY EM or EOM to IZERVAY EM at 3.5 years
- 1.83 mm2 in participants treated with IZERVAY EM following sham
And how was the therapy tolerated?
Similar to prior clinical findings, IZERVAY was “well-tolerated” and had:
- No new safety signals
- No cases of retinal vasculitis or occlusive vasculitis
- No increased risk for intraocular inflammation
Nice! So, while we're on the subject … any other new data to be aware of?
Yes, actually—two more datasets supporting extended IZERVAY’s safety, tolerability, and efficacy:
- A real-world, retrospective study of patients receiving IZERVAY during its first year of FDA approval, with data obtained from the American Academy of Ophthalmology Intelligent Research in Sight (IRIS) Registry
- The findings: See here for those details.
- A post-hoc analysis of pooled 18-month data from the GATHER1/GATHER2 studies examining the relationship between structure and function in GA via analyzing two key areas in patient eyes treated with IZERVAY: ellipsoid zone (EZ) integrity and low luminance deficit (LLD).
- The findings: See here for those details.