A California retinal specialist argues in a JAMA Ophthalmology viewpoint article that an independent panel of retinal specialists and statisticians should assess the data from clinical trials of Syfovre (pegcetacoplan) because of the lack of a complete FDA scientific analysis of the drug and of peer-reviewed publication.
An independent panel of retinal specialists and statisticians should assess the clinical trial data for Syfovre (pegcetacoplan injection) and provide an unbiased evaluation of the drug in light of the lack of peer-review publication and a complete FDA review, argues Ira Schachar, M.D., M.Sc., the author of an opinion piece published today in JAMA Ophthalmology.
Schachar also suggests that widespread use of Syfovre should wait until there is a complete FDA scientific analysis of the drug or a peer-reviewed publication of the study results. He says the data released by Apellis Pharmaceuticals raises methodological questions and he questions whether “repeated measures and missing data have been appropriately handled.” Schachar, who was an assistant professor at Stanford prior to joining the North Bay group, says in the one-page viewpoint piece that questions about the Syfovre statistics are “particularly important” because of the high dropout rates from two important, phase 3 trials for the drug called OAKS and DERBY.
When the FDA approved Syfovre in February 2023 it was the first FDA-approved treatment for geographic atrophy, one of the two forms of late-stage “dry” age-related macular degeneration. Geographic atrophy is leading cause of blindness. According to the American Academy of Ophthalmology (AAO), worldwide, more than 8 million people are affected by the condition.
Clinicians and professional societies have flagged safety concerns about Syfovre. In July 2023, the American Society of Retinal Specialists’ Research and Safety in Therapeutics committee issued a warning about six cases of retinal vasculitis associated with Syfovre.
In October, Amr Dessouki, M.D., a retinal specialist in Campbell, California, and his colleagues, reported a case series in JAMA Ophthalmology showing that nearly one-third of patients treated with Syfovre developed symptomatic floaters. At the AAO annual meeting in November, a retinal fellow at the Wolfe Eye Clinic in Iowa gave a presentation on five patients who experienced side effects from Syfovre, including a 96-year-old patient who experienced hemorrhagic occlusive vasculitis-type inflammation and was left with no light perception in the treated eye.
In August 2023, Apellis recommended that clinicians discontinue use of a certain type of needle in the Syfovre injections and stopped distributing that type of needle after it discovered “internal structural variations” in that needle. However, the company said a causal relationship had been established between that needle and the “rare events of retinal vasculitis.”
On Oct. 21, 2023, lead author Jeffrey S. Heier, M.D., of Ophthalmic Consultant of Boston, and his colleagues reported positive results from the OAKS and DERBY trials in Lancet and in the conclusion of the abstract they characterized the safety profile as “acceptable.”
Serious ocular treatment-emergent adverse events were reported in five (2%) of the 213 patients randomly assigned to monthly injections, four (2%) of 212 of those assigned to every other month injections, and one (less than 1%) of 211 patients assigned to the sham treatment in the OAKS trial, Heier and his colleagues reported.
In the DERBY trial, the number of serious ocular treatment-emergency adverse was similar: Four (2%) of 206 in the monthly treatment group, two (1%) of 208 in every other month groups, and two (1%) of 206 patients in the sham group, they reported.
The OAKS and DERBY trials were funded by Apellis, and graphic atrophy lesion growth were their primary end points. At 24 months, Syfovre monthly and every other month slowed geographic atrophy lesion growth by 22% and 18% in OAKS trial and by 19% and 16% in DERBY trial, respectively, compared with sham, Heier and his colleagues reported.
However, the choice of that end point has been controversial because it is anatomical measurement not a measurement of vision as experienced by patients. Heier and colleagues reported that there were no differences among the monthly treatment, every-other-month treatment or sham study groups in the OAKS and DERBY trial in key visual function end points at 24 months.