Apellis Pharmaceuticals will provide an update with 18-month data on its phase 2 trial (FILLY) of its complement C3 inhibitor, APL-2, in patients with geographic atrophy (GA) associated with age-related macular degeneration (AMD).
The company previously reported that APL-2 met its primary endpoint of reducing the growth rate of the GA lesion (measured as square root transformation of GA lesion area) compared to sham after 12 months of treatment. APL-2 administered monthly via intravitreal injection showed a 29% (P = 0.008) reduction in the rate of GA lesion growth compared to sham after 12 months of treatment. With every other month administration of APL-2, a 20% (P = 0.067) reduction was observed. Statistical significance was defined as P < 0.1 for this study. After the 12 month dosing period, subjects were followed for a further 6 months without treatment. During this period of non-treatment, the GA lesions in the previously treated groups grew at a rate similar to sham. Subjects previously treated with monthly APL-2 showed only a 12% reduction over the 6-month period compared to sham, while those previously treated with every other month APL-2 showed a 9% reduction compared to sham.
Rishi Singh, MD, Staff Surgeon at the Cole Eye Institute at the Cleveland Clinic, said, “The 18-month results of the FILLY trial support the positive effect seen at 12 months. In the FILLY trial, APL-2 significantly reduced the growth of GA, and may for the first time offer these patients hope of preserving their vision. We eagerly anticipate the start of the phase 3 trials.”
No changes in the safety profile were observed in the 12-18 month period. Over the full 18-month study period, a total of 26 cases of exudative AMD were reported by the investigators. These were seen more frequently in the APL-2-treated patients (18 in the monthly treatment group, 7 in the every other month treatment group and 1 in the sham control group). No negative impact on visual acuity was observed.
“Geographic atrophy is a blinding disease, and today there are no approved treatment options for patients,” Cedric Francois, MD, PhD, founder and chief executive officer of Apellis, said in a company news release. “We are pleased that the 18-month data support that the statistically significant effect we observed in the first 12 months of the study was the result of the biological activity of APL-2.”
The 18-month results of the FILLY trial will be presented by Dr. Singh at the 41st Annual Meeting of the Macula Society in Beverly Hills, CA at 11:17 AM PST on Thursday, February 22. The data presented by Dr. Singh will be made available on the Apellis web site at the time of the presentation.
The company previously announced that, following discussions with FDA in December, it has finalized its phase 3 protocol for APL-2 for the treatment of GA. The phase 3 program, planned to begin in the second half of 2018, will consist of two identical 600-patient prospective, multicenter, randomized, double-masked, sham-injection controlled studies to assess the efficacy and safety of multiple intravitreal (IVT) injections of APL-2 in patients with GA. The phase 3 trials will be similar in design to the phase 2 FILLY trial, including the eligibility criteria and primary endpoint of GA lesion growth at 12 months. Patients whose treatment eye develops exudative AMD will continue to be treated with APL-2 along with VEGF inhibitors, the current standard of care for exudative AMD.
About the FILLY trial
The FILLY trial is a 246-patient phase 2 multicenter, randomized, single-masked, sham-controlled clinical trial of APL-2 in patients with GA conducted at over 40 clinical sites, located in the United States, Australia, and New Zealand. APL-2 was administered as an intravitreal injection in the study eye monthly or every other month for 12 months, followed by 6 months of monitoring without active treatment until month 18. Eyes were evaluated for GA by fundus autofluorescence photographs (FAF). The rate of GA area growth was measured from baseline to month 18. The primary efficacy endpoint was the change in GA lesion size from baseline to month 12, compared to sham.