Apellis Pharmaceuticals, Inc. released new data from the GALE long-term extension study assessing 30 months of continuous treatment with Syfovre (pegcetacoplan injection) 15 mg/0.1mL in patients with geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD).
Give me a quick refresh on Syfovre.
Syfovre was approved by the FDA in February 2023 as the first and only treatment for GA.Per the prescribing information, a 15 mg (0.1 mL out of a 150 mg/mL solution) single-dose vial is to be intravitreally administered into each affected eye once every 25 to 60 days.
Click here for a rundown on how it works.
How did it perform in prior trials?
The phase 3 DERBY and OAKS studies compared Syfovre’s efficacy and safety as monthly and bi-monthly injections with the use of sham injections for 24 months.
Both monthly and bimonthly injections showed a clinically meaningful reduction—36% and 29% in DERBY as well as 24% and 25% in OAKS—in GA lesion growth when compared to the sham injections from months 18 to 24.
What else?
Post-hoc analyses from the phase 3 trials—released in April 2023—supported the use of Syfovre, with 46% of patients in both DERBY and OAKS trials receiving bi-monthly injections demonstrating a clinically meaningful reduction in the loss of photoreceptor cells.
Meanwhile, 20% (OAKS) and 21% (DERBY) experienced a clinically meaningful reduction in retinal pigment epithelium (RPE) cell loss.
Go on …
Similarly, 53% (OAKS) and 47% (DERBY) of patients receiving monthly injections experienced a clinically meaningful reduction in the loss of photoreceptor cells ,while 22% (OAKS) and 27% (DERBY) experienced a clinically meaningful reduction in RPE cell loss.
See here for more details.
Now talk about this 30-month data.
Overall, the GALE extension study exhibited Syfovre’s continuous improvement in efficacy through 30 months for both monthly and bimonthly injections—consistent with the DERBY and OAKS trials.
Were sham-treated patients included?
Yup! The sham patients from both original phase 3 trials were allowed to transition to receiving Syfovre in the extension study after Month 24; a projected sham arm was used to gauge GA lesion growth as treatment for the remaining 6 months (to Month 30).
Give me some numbers.
Apellis reported that Syfovre reduced lesion growth for both monthly (39%; p<0.0001) and every-other-month (EOM) (32%; p<0.0001) injections vs the projected sham arm (all p-values nominal).
To note, the treatment time period assessed was from Month 24 to Month 30.
What else? Syfovre was also found to reduce GA lesion growth by up to 45% (monthly) and 33% (every-other-month) in patients with nonsubfoveal lesions.
How about AMD and IOI?
According to the company, the rate of exudative AMD was consistent with the phase 3 data: 7.5 and 7.2 events (monthly); 3.9 and 3.6 events (bimonthly), with each rate per 100 patient years at Months 24 and 30.
The reported rate of intraocular inflammation (IOI) was 0.26% per injection for all Syfovre-treated patients in the phase 3 program.
Any adverse events?
No non-serious adverse events (SAEs) of ischemic optic neuropathy (ION) were reported for both treatment groups; however, one SAE of ION was noted in the monthly group.
Further, no cases of endophthalmitis were observed.
And the big question: any cases of retinal vasculitis?
Understandable, especially given the ASRS’s announcement from last month (as well as Apellis’s recent update).
But nope; no cases of retinal vasculitis were observed in the drug’s clinical program.
Significance?
This latest consistency of the GALE long-term extension study data compared to previous trials (in regards to efficacy and safety) can support the potential use of Syfovre for GA patients on an extended basis for treatment.