According to the ASRS Research and Safety in Therapeutics (ReST) Committee, a small number of cases of occlusive retinal vasculitis has been observed between 7 and 13 days after injection for pegcetacoplan (Syfovre). In their email, the ReST Committee commented that, “the etiology of these events is unclear, and outcomes in these patients are still evolving”. It is understood that the manufacturer of pegcetacoplan (Apellis Pharmaceuticals) has distributed an estimated 60,000 vials of the drug since FDA approval, according to the ASRS memo to members. No further information is not yet available by either the manufacturer or the FDA.
Pegcetacoplan was approved by the FDA in February 2023 for a targeted complement C3 therapy designed to regulate excessive activation of the complement cascade. The treatment is aimed to reduce the growth of lesions in the retina of patients diagnosed with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). In the original approval supported by two phase 3 trials (OAKS and DERBY), at 24 months in the OAKS study (637 participants), monthly injections slowed GA lesion growth by 22 percent, and injections administered every-other-month (EOM) slowed GA lesion growth by 18 percent. In addition, at 24 months in the DERBY trial (621 participants), monthly injections slowed lesion growth by 18 percent and injections administered EOM slowed lesion growth by 17 percent. More importantly, intraocular inflammation was noted in 2.1% (EOM) to 3.8% (monthly) of pegcetacoplan patients at 24 months.
According to commentary from Fierce Pharma (an industry news outlet), the ASRS’ observation of the vasculitis was not related to a specific batch of product but that the side effect began prior to 7 to ~14 days after a patient’s first injection. Consequently, Fierce Pharmawas understood that ASRS urged vigilance and close follow-up after administration. Regardless, the stock price of the company (Apellis) showed a significant reduction, from a high of $84.50, closing on Jul 14th, to a close of $34.39 on Friday, Jul 21st, a fall of almost 60%. Pegcetacoplan costs $2,190 per vial and, according to the recent Apellis annual report for FY2022, the company estimates there are at least five million people worldwide living with GA, including more than one million people in the US. This is a very large market size, potentially to be a “blockbuster”, a $1bn sales revenue per year. As more information on the vasculitis is collected in due course, time will tell how real-world data will impact on patients and industry in the coming months.