Amid Favorable Results, Questions About Syfovre’s Safety | ASRS 2023

Questions about its safety continued to roil the prospects of Syfovre (pegcetacoplan injection) today even as favorable results from an open-label, extension study showed the new drug for geographic atrophy seems to have a stronger effect the longer it was used.

Two weeks ago, the ASRS Research and Safety in Therapeutics (ReST) committee issued a warning about six cases of retinal vasculitis associated with Syfovre, a heralded treatment because it is the first FDA-approved one for geographic atrophy, a late-stage type of macular degeneration that affects about 1 million people in the U.S.

Yesterday, the drug’s maker, Apellis Pharmaceuticals, issued a news release that said the company had identified seven cases of retinal vasculitis associated with its drug and was investigating another. The company said its review had not identified any quality issues with manufacturing processes or contamination and that the side effect was not associated with any particular manufacturing lot. The company also said in the news release that there had been no changes in the formulation between the product used in clinical trials and the product distributed after the FDA approved the treatment on Feb 17., 2023. No cases of retinal vasculitis were reported among the clinical trials that led to Syfovre’s approval.

Nathan Steinle, M.D., presenting the Gale extension study results for Syfovre (pegcetacoplan injections) results today at the meeting of the American Society of Retina Specialists in Seattle. He said that retinal vasculitis is an "extremely rare event" that occurs once in every 10,000 injections

Nathan Steinle, M.D., a retina specialist at California Retina Consultants in central California, said during his presentation of the first six months of the extension study, called Gale, that the “totality of the data show this is an extremely rare event” that and that retinal vasculitis occurs once in every 10,000 injections.

During the question period after his presentation at the American Society of Retina Specialists annual scientific meeting, Steinle was asked whether the rate per total injections was “falsely reassuring” because most of the cases have occurred after first injections and therefore first injections should be the denominator when figuring the rate. Steinle said “any which way you cut the data” it seemed to be about the same rate.

But Steinle said as a result of the news about the instances of retina vasculitis, he had changed his personal practice so he doesn’t treat both eyes with Syfovre on the same day.

Another panelist, Sunir J. Garg, M.D., a retina specialist at Wills Eye Hospital in Philadelphia, said he also had gotten more cautious, treating one eye at a time and would perhaps hold off on treating some patients with Syfovre until more data is reported.

The Gale extension study includes 83% of the patients that had volunteered to participate in the Oaks and Derby trials that led to Syfovre’s approval, according to Steinle. People who were treated with Syfovre in those trials, either on a monthly or every other month basis, are continuing with those regimens in the Gale study. The people who were treated with a sham (placebo) treatment have been “crossed over” to receive Syfovre. Steinle emphasized that all the participants in the Gale study are receiving the active treatment, Syfovre.

Steinle showed data comparing the rate of geographic atrophy lesion growth among the Gale participants relative to a projection of what the growth would have been if they had continued on the sham. The data presented by Steinle show a 24% reduction in lesion growth relative to the projected sham at 30 months among those receiving a monthly injection and a 21% reduction in those receiving a Syfovre injection every other month. He noted that the relative reduction in lesion growth increased with time, so it was greater in the 24-30 month period of the trial that it was earlier on.

Steinle also presented data for the 272 participants who were switched from sham to Syfovre that showed a 15% reduction in the growth of geographic atrophy lesions after the study volunteers were treated with Syfovre instead of the sham.