Just 5 months after the FDA approved Apellis Pharmaceuticals’ Syfovre (pegcetacoplan injection) 15 mg/0.1 mL for the treatment of geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD), the American Society of Retina Specialists (ASRS) has noted that there are reported cases of occlusive retinal vasculitis associated with its use.
Refresh me on Syfovre.
Syfovre is currently the first and only FDA-approved therapy for GA.
Via intravitreal injection, it works as a C3 inhibition therapy to regulate excessive activation of the complement cascade (part of the immune system), which could lead to the onset and progression of diseases such as GA.
See here for a visual.
What’s the recommended dosage?
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.
Gotcha. Now what did ASRS report?
According to a notification from the ASRS Research and Safety in Therapeutics (ReST) Committee to ASRS members on July 15, 2023, physicians have reported intraocular inflammation (IOI) in patients following a first injection of Syfovre.These reports include mild-to-moderate and severe IOI as well as cases of retinal vasculitis and occlusive retinal vasculitis.
As of July 15 2023, ASRS has received notification of six cases of occlusive retinal vasculitis.
When exactly did these adverse events appear?
Per ASRS, the events were observed between 7 and 13 days following the first injection.
Further, no specific lot of Syfovre was connected to these AEs.
How many vials have been distributed so far?
According to Apellis, 60,000 vials since its FDA approval, ASRS reported.
Were they reported in clinical trials?
Not exactly.
A small percentage of patients in the phase 3 DERBY and OAKS trials (2.1% for every-other-month injections; 3.8 for monthly injections) reported IOI at 24 months.
These included ocular discomfort, neovascular AMD, vitreous floaters, and conjunctival hemorrhage.
However, among these reports, there were no occurrences of retinal vasculitis.
See here for post-hoc analysis findings.
What else?
Per the ASRS notification, Apellis has already “reviewed images and clinical data from all cases of IOI from their clinical trials and no cases of retinal vasculitis were found on secondary review of those patients.”
Interesting … so what is the company saying?
According to an Apellis spokesperson, since its February 2023 approval, the real-world safety profile of Syfovre has been consistent with clinical studies.
Further, “There have been rare events of [IOI] with retinal vasculitis in the real world at an estimated 0.01% per injection,” the spokesperson wrote in a July 18, 2023, email to Glance.
And their next steps?
Per the spokesperson, the company is in the process of “thoroughly investigating all cases with external experts, including real-world procedure technique and potential risk factors.”
They also stated that, “patient safety is our top priority, and we take any (AEs) seriously.”
What other effects has this news had?
In the wake of the news, the company’s stock price (APLS) sank nearly 40% to $52.46 by the end of the day on July 17, 2023—an amount well below its 50-day moving average, Investor’s Business Daily reported.
As of 12:45 pm EST on July 18, Apellis’ stock price has sunk even lower, to $40.19.
What if my patients are experiencing AEs from Syfovre?
The ASRS recommends physicians report all AEs to the ReST Committee by clicking here as well as to the drug’s manufacturer and FDA Medwatch.