The Lancet has published 24-month results from two phase 3 trials evaluating Apellis Pharmaceuticals, Inc’s Syfovre (pegcetacoplan injection) 15 mg/0.1 mL for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
Hold up … Syfovre is approved, right?
Yup! The FDA approved Syfovre for commercial distribution in February 2023 which was at the time the first and only approved therapy for GA for use beyond 12 months (click here for some background, including a visual on how it works).
The formulation is designed as a 15 mg/0.1 mL dose to be administered by intravitreal injection once every 25 to 60 days into each affected eye to potentially reduce the progression of GA.
And the elephant in the room …
We’ll address it: back in July 2023, the American Society of Retina Specialists (ASRS) reported cases of retinal vasculitis associated with the first injection of Syfovre in GA patients.
In response, Apellis launched an investigation into the reports of retinal vasculitis, later confirming a total of eight cases (five occlusive, three non-occlusive).
Ok, now to these clinical trials.
The DERBY and OAKS studies were randomized, double-masked, and sham-controlled, with 621 (OAKS; NCT03525613) and 637 patients (DERBY; NCT03525600) enrolled.
Both studies compared Syfovre’s efficacy and safety with the use of sham injections on a monthly and every-other-month (EOM) basis in patients with GA, with patients randomly assigned (2:2:1 ratio).
Investigators assessed the change in the total area of GA lesions from baseline measured by fundus autofluorescence at 12 months. Patients continued to receive masked treatment for 24 months.
Dr. Wykoff explains further below.
Let’s start with the post-hoc analysis.
Released in April 2023, the post-hoc analyses from both phase 3 trials found that Syfovre provided visual function and quality-of-life (QoL) benefits, as well as a clinically meaningful reduction in the loss of retinal pigment epithelium (RPE) and photoreceptor cells.
See here for our coverage.
And the newly-published data?
Per the publication, both EOM and monthly Syfovre showed a clinically meaningful reduction of GA lesion growth with increasing effects over time as well as a well-demonstrated safety profile.
Dr. Wkyoff discusses both efficacy and safety of the therapeutic below.
Give me some 24-month numbers.
In OAKS, GA lesion growth slowed by 22% (monthly) and 18% (EOM).In DERBY, GA lesion growth slowed by 19% (monthly) and 16% (EOM).
To note, no significant differences in key secondary visual function endpoints were observed.
How did this compare to 12-month data?
In OAKS, GA lesion growth slowed by 21% (monthly) and 18% (EOM).In DERBY, GA lesion growth slowed by 12% (monthly) and 11% (EOM).
Any adverse effects?
In OAKS, ocular treatment-emergent adverse events (TEAEs) were reported in:
- 2% of 213 patients (monthly)
- 2% of 212 patients (EOM)
- <1% 211 patients (sham)
And in DERBY:
- 2% of 206 patients (monthly)
- 1% of 208 patients (EOM)
- 1% 206 patients (sham)
Of interest: new non-exudative AMD was noted in the following:
- OAKS
- 11% (monthly)
- 8%(EOM)
- 2% (sham)
- DERBY
- 13% (monthly)
- 6%(EOM)
- 4% (sham)
Gotcha. So which patients are the. best candidates for Syfovre?
Dr. Wkyoff has the need-to-know criteria on three distinct patient groups.
Significance?
Per Apellis, this data supports the use of Syfovre in demonstrating clinically meaningful reductions in GA lesion growth in as little as six doses a year.