Apellis Reviewing Retinal Vasculitis Cases in Pegcetacoplan-Treated GA Patients

Apellis Pharmaceuticals provided an update over the weekend regarding the occurrence of retinal vasculitis among patients treated with pegcetacoplan intravitreal (IV) injection (SYFOVRE), the company’s complement inhibitor therapy indicated to treat geographic atrophy (GA).¹

A total of 7-8 cases of the rare adverse event occurred since the therapy had been made available after its February approval by the US Food and Drug Administration (FDA)—2 each in April and May, 3 in June, and a potential other case being evaluated by Apellis—the company stated in a release Monday. Four of the 7 cases were occlusive.

“Apellis has been conducting a thorough evaluation following these reported events, including a review of the SYFOVRE manufacturing process and drug product and of the safety data from the Company’s phase 3 clinical trials of SYFOVRE,” the company stated. “There were no changes in the formulation of the product between phase 3 clinical trials and commercial supply.”

Thus far, the company has observed no indication of issue within the drug product’s manufacturing nor clinical profile that would associate with the risk of developing retinal vasculitis. They noted that zero events of retinal vasculitis were reported by investigators nor independent reviewers of pegcetacoplan’s pivotal phase 3 trial data.

A sight-threatening condition, retinal vasculitis may be characterized by a series of local or systemic inflammatory disorder complications driving retinal vessel inflammation. It is estimated to occur in 1 - 2 patients per 10,000 annually.²

Cedric Francois, MD, PhD, co-founder and chief executive officer of Apellis, stressed safety remaining “the top priority” of the company during this review stage.

“Following 68,000 commercial vials distributed and 23,000 clinical trial injections to date, these events continue to be very rare,” Francois said in the company’s statement. “Additionally, as part of our ongoing review, we have seen no indication that drug product or manufacturing issues contributed to these events.”¹

The company presented new data regarding pegcetacoplan’s clinical efficacy and safety during the American Society of Retina Specialists (ASRS) 2023 Annual Meeting in Seattle this weekend. In one such report from the GALE long-term extension trial, pegcetacoplan was associated with ≤45% reduction in nonsubfoveal GA lesion growth versus IV sham injection between months 24 - 30.³

Presenting investigator Nathan Steinle, MD, of California Retina Consultants, discussed Apellis’ report in an interview with HCPLive. Steinle stressed the familiarity of pegcetacoplan among investigators and prescribers, and its supporting database including ≤23,000 injections administered in clinical trials.

“So we have a very large database to look to, to see how patients respond to this molecule,” Steinle said. “It's a very well-known molecule to us.”

That said, Steinle did note the need for vigilance with new molecules entering the market, such as the first-in-class pegcetacoplan.

“With any molecules that come forward, of course, we're looking for these very rare events,” he said. “And the overall calculated incidence of this vasculitis up to this point is in the order of 1 in 10,000 injections, making it exceedingly rare.”

The ASRS Research and Safety in Therapeutics Committee acknowledged physician reports of mild-to-moderate intraocular inflammation, along with retinal vasculitis, among patients treated with pegcetacoplan approximately 2 weeks ago.

“The etiology of these events is unclear, and outcomes in these patients are still evolving,” the ASRS committee wrote. “The ASRS urges practitioners to carefully inspect the eye for any sign of intraocular inflammation prior to injection of Syfovre and to defer administration when any concern signs of inflammation are present.”⁴

The FDA is anticipated to make a New Drug Application (NDA) ruling on competitor complement inhibitor avacincaptad pegol from Iveric Bio for the treatment of GA later this month.⁵

References

1. ^{Apellis. Apellis Provides Update on Review of Rare Safety Events with SYFOVRE® (pegcetacoplan injection) for Geographic Atrophy. News release. Published July 29, 2023. https://investors.apellis.com/news-releases/news-release-details/apellis-provides-update-review-rare-safety-events-syfovrer}
2. ^{Okeefe GD, Kim LA, Agarwal A, Tripathy K, et al. Retinal Vasculitis. American Academy of Ophthalmology; EyeWiki. Last updated on June 17, 2023. https://eyewiki.aao.org/Retinal_Vasculitis#:~:text=Retinal%20vasculitis%20can%20be%20an,immune%2C%20inflammatory%20or%20neoplastic%20disorders.}
3. ^{Iapoce C. Nathan Steinle, MD: Long-Term Efficacy of Pegcetacoplan in GALE Extension Study. HCPLive. Published June 30, 2023. https://www.hcplive.com/view/nathan-steinle-md-long-term-efficacy-pegcetacoplan-gale-extension-study}
4. ^{@surgeonretina.First-in-class newly FDA approved dry #maculardegeneration drug #Syfovre linked to RARE cases of severe inflammation via @asrsdocs “In addition to cases of mild-moderate intraocular #inflammation… reports have also included [6] cases of severe intraocular inflammation, #retina#vasculitis, occlusive retinal vasculitis.” #Ophthalmology. July 15, 2023. Accessed July 31, 2023. https://twitter.com/surgeonretina/status/1680364644563550209?s=46}
5. ^{Kunzmann K. 6 FDA Decisions Expected Before 2024. HCPLive. Published July 5, 2023. https://www.hcplive.com/view/6-fda-decisions-expected-before-2024}