乌鸦传媒

SEATTLE -- Reports of unexpected panuveitis and retinal occlusive vascular disease associated with pegcetacoplan (Syfovre) treatment has triggered a search for answers by ophthalmologists and the drug's manufacturer.

Since July 3, the American Society of Retina Specialists (ASRS) Research and Safety in Therapeutics (ReST) Committee has learned of seven cases of retinal inflammation and vascular occlusive disease. The reports provided little insight into the potential causes, according to a summary report here at the annual meeting.

"In summary, we don't know what this is," said Andre Witkin, MD, of the New England Eye Center of Tufts Medical Center in Boston, and chair-elect of the ReST Committee. "We don't know what the etiology is. We will keep you all informed of any new details that we may be able to provide."

Providing a brief timeline of a rapidly evolving situation, Witkin said ReST received the first report on July 3, involving a woman, age 67, who received a first dose of pegcetacoplan on June 20. Nine days later she had worsening vision, associated with corneal edema and fibrin but no inflammatory cells in the anterior chamber (hypopyon). Fluorescein angiography showed clear signs of peripheral vascular nonperfusion and vasculitis, said Witkin.

Sixteen days later, further deterioration had occurred, as the patient had macular whitening and vision had declined to light perception. The final classification of the patient's condition was panuveitis with retinal occlusive vasculitis.

Two days after ReST received the initial report, drug manufacturer Apellis Pharmaceuticals contacted ReST to discuss safety concerns. During the next week, ReST received additional reports of pegcetacoplan-associated retinal inflammation and vascular occlusion. ReST and Apellis officials met July 12 to discuss the cases, and on July 15, ASRS sent a memo to its membership, alerting ophthalmologists of the adverse events.

In the memo, ReST noted that all the cases to date had arisen 7-13 days after the initial dose of pegcetacoplan. The memo stated that the etiology remained unclear and that patient outcomes continued to evolve.

The total number of reports of pegcetacoplan-associated intraocular inflammation reviewed by ReST has reached 21, said Witkin. Classifications assigned to the cases included 17 cases of panuveitis, seven cases of retinal vasculitis, and seven of occlusive vasculitis.

Apellis estimated that 68,000 vials of pegcetacoplan have been distributed to date. In response to a question from the audience, Witkin said the number of vials used to date remains unclear.

ReST also has received 23 reports of intraocular inflammation related to use of faricimab (Vabysmo). In 12 cases, the inflammation was classified as panuveitis and two were classified as retinal occlusive vasculitis. Globally, Roche/Genentech has received 218 reports of intraocular inflammation related to faricimab treatment, nine classified as retinal vasculitis and four as retinal occlusive vasculitis. According to Witkin, the company has distributed an estimated 1,180,000 vials of faricimab worldwide, 900,000 in the U.S.

Current ReST Committee chair Richard Kaiser, MD, of Thomas Jefferson University in Philadelphia, said the Apellis and its safety team "have been very open and transparent in working with ReST to see if we can understand the root cause of this and really figure out what's going on."

In a that coincided with Witkin's report, Apellis stated that there is "No indication that drug product or manufacturing issues contributed to rare events of retinal vasculitis...Zero events were reported in clinical trials, following more than 23,000 clinical trial injections to date."

"Additionally, as part of our ongoing review, we have seen no indication that drug product or manufacturing issues contributed to these events," said Apellis CEO Cedric Francois, MD, PhD, in the release. "We will continue to collaborate with the retina community to deliver a safe, effective treatment for GA [geographic atrophy]."

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