Summary of Cancellation for Syfovre (pegcetacoplan)

The purpose of this New Drug Submission (NDS) was to obtain market authorization for Syfovre (pegcetacoplan) 15 mg solution for intravitreal injection, for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration.

The sponsor submitted drug quality, pre-clinical and clinical components. The submission was reviewed using the international review work-sharing model with the Access Consortium. Health Canada reviewed the Clinical Module, the Australian Therapeutic Goods Administration (TGA) reviewed the Quality Module, and SwissMedic reviewed the Non-Clinical Module. All agencies, and the United Kingdom’s Medicines and the Healthcare products Regulatory Agency (MHRA), participated as peer reviewers of all modules.

The pivotal safety and efficacy of Syfovre was evaluated in two near-identical phase 3 international, randomized, double-masked, sham controlled pivotal studies (study 303 [DERBY] and study 304 [OAKS]). 839 patients with GA (with or without subfoveal involvement) were treated with intravitreal (IVT) pegcetacoplan 15 mg/0.1 mL either monthly (PM: DERBY – 206; OAKS – 213) or every other month (PEOM: DERBY – 208; OAKS – 212) and compared to 419 patients in a pooled sham control group (DERBY – 207; OAKS – 212) for 24 months. The primary efficacy endpoint for both DERBY and OAKS was to assess the change in the rate of GA lesion growth from baseline as measured by fundus autofluorescence (FAF) at month 12. The key secondary efficacy endpoints encompassed all functional visual testing at month 24, including best corrected visual acuity (BCVA), reading speed, a functional reading independence composite score and mesopic microperimetry (OAKS only). The safety dataset for the two pivotal studies included the same number of patients as listed above and was evaluated at 12 months and again at 24 months.

The Sponsor received a Notice of Non-compliance (NON) on December 22, 2023. In the response to NON (submitted June 26, 2024), to address the major objections pertaining to both efficacy and safety identified from the initial pivotal studies (DERBY and OAKS), the Sponsor submitted interim results from study 305 (GALE) which was a phase 3, open-label, multicenter, interventional long-term extension study. GALE was designed primarily as a safety extension study. This study derived patients from DERBY and OAKS, but also from the phase 1b study 103. Patients either continued their same dosing regimen from their entry study (in either the PM or PEOM group) or crossed-over from a sham group to treatment group (i.e. SM to PM or SEOM to PEOM). These crossover patients made up the new “sham” groups but were also undergoing active treatment, with a start time of treatment at 24 months after their original trial enrollment. A total of 782 patients from DERBY and OAKS were included in the analysis (n = 241 PM; n = 268 PEOM; crossed-over PM n = 129 and crossed-over PEOM n = 144).

At the time of the cancellation, the review of the submission was complete. Health Canada had identified ongoing deficiencies in the data that would have precluded issuing an approval. The Sponsor chose to cancel their submission.

There is no expected impact for patients using SAP or in clinical trials.

Requests for special access to Syfovre will continue to be considered on a case-by-case basis.  For more information about the Special Access Programme refer to the programme’s web site:  http://www.healthcanada.gc.ca/sap  or http://www.santecanada.gc.ca/pas