The American Society of Retina Specialists (ASRS) has received reports of at least six cases of occlusive retinal vasculitis following injection of pegcetacoplan (Syfovre) into the eye.

In an email to members dated July 15, the ASRS Research and Safety in Therapeutics (ReST) committee noted that the reported events were observed between 7 and 13 days after injection, with no specific drug lots implicated.

“The etiology of these events is unclear, and outcomes in these patients are still evolving,” the email stated.

The notification came almost 5 months to the day after the US Food and Drug Administration approved pegcetacoplan as the first intravitreal treatment for geographic atrophy, an advanced form of dry age-related macular degeneration (AMD). Several treatments for neovascular, or “wet” AMD, have been in use for more than a decade. Prevent Blindness estimates that around 3 million Americans aged 55 years or older have some form of intermediate or advanced AMD, of whom 85%-90% have the untreatable dry form.  

Pegcetacoplan targets deposits of complement factor 3 (C3) found within drusen, the yellowish patches on the retina that consist of lipids, proteins, and cellular debris. Drusen contribute to vision loss in people with retinal diseases such as AMD. C3 acts as an intersection of the complement pathways that contribute to GA.  

Apellis Pharmaceuticals, the manufacturer of pegcetacoplan, has distributed an estimated 60,000 vials of the drug since FDA approval, according to the ASRS memo to members.

The pivotal phase 3 DERBY and OAKS trials reported rates of intraocular inflammation (IOI) at 24 months of 3.8% and 2.1% in eyes injected monthly and every other month, respectively, vs. 0.2% in the placebo group.

The ASRS said in its memo that the trial findings included four cases of endophthalmitis, a bacterial infection that causes inflammation of the sclera, and four cases of severe IOI. However, the trials did not report any cases of retinal vasculitis.

In a statement to Medscape Medical News, Apellis said the rate of retinal vasculitis in real-world use was about 0.01% per injection.

“We are in the process of thoroughly investigating all cases with external experts, including real-world procedure technique and potential risk factors,” the statement read.

The ASRS advised clinicians to use the injection kit that comes with pegcetacoplan and to follow sterile practices. Injection is contraindicated in people with active intraocular inflammation, according to the FDA. Ophthalmologists should inspect the eye for any sign of intraocular inflammation before injection.

Call for “Vigilance”

Demetrios G. Vavvas, MD, PhD, an outspoken critic of pegcetacoplan as a treatment for GA, told Medscape Medical News that no known biology explains causation between the drug and occlusive vasculitis.

“People have hypothesized that it may be manufacturing, though the cases did not share lot numbers as per [the] ASRS announcement,” Vavvas, director of the Retina Service at Harvard Medical School and co-director of the Ocular Regenerative Medical Institute at Massachusetts Eye and Ear Infirmary and Mass General Hospital in Boston, told Medscape by email.

“Other people have hypothesized that it may be procedural because doctors have to draw the viscous drug themselves,” Vavvas added. “It is hard to envision how drawing the drug, something that doctors have done millions of times with other injectable drugs, will lead to occlusive vasculitis.”

Following the ASRS notification, Vavvas said ophthalmologists should remain “vigilant” when using pegcetacoplan “and inform the patients to return to care as soon as possible if they start to experience any symptoms.”

He recommended fluorescein angiography to find early signs of vasculitis, and aggressive treatment with anti-inflammatory drugs.

Vavvas reported no relevant financial relationships.

Richard Mark Kirkner is a medical journalist based in the Philadelphia area.

Source: Read Full Article