Data supports biologic activity of APL-2 in reducing the growth rate of geographic atrophy
CRESTWOOD, Ky. and CAMBRIDGE, Mass. - Apellis Pharmaceuticals, Inc. (Nasdaq:APLS), a clinical-stage biopharmaceutical company developing a platform of novel therapeutic compounds for the treatment of autoimmune diseases, today 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 six 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 six 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,” commented Cedric Francois, MD, PhD, founder and chief executive officer of Apellis. “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 22nd. 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 six 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.
APL-2 is designed to inhibit the complement cascade centrally at C3, and may have the potential to treat a wide range of complement-mediated diseases more effectively than is possible with partial inhibitors of complement. APL-2 is a synthetic cyclic peptide conjugated to a polyethylene glycol (PEG) polymer that binds specifically to C3 and C3b, effectively blocking all three pathways of complement activation (classical, lectin, and alternative). In addition to the FILLY trial in GA, Apellis is currently evaluating APL-2 in two clinical trials for systemic administration in paroxysmal nocturnal hemoglobinuria (PNH). Interim data from these trials demonstrated meaningful improvements in lactate dehydrogenase and hemoglobin levels in previously untreated patients as well as patients who are suboptimal responders to eculizumab, the current standard of care in the treatment of PNH. Phase 3 studies are planned in GA and PNH, and future clinical studies of APL-2 are anticipated in other diseases in which complement is implicated.
About geographic atrophy (GA)
GA is an advanced form of age-related macular degeneration (AMD), a disorder of the central portion of the retina, known as the macula, which is responsible for central vision and color perception. GA is a chronic, progressive condition that leads to central blind spots and permanent loss of vision. Based on published studies, we estimate that approximately one million people have GA in the United States alone. There are currently no approved treatments for GA.
Apellis Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on the development of novel therapeutic compounds for the treatment of a broad range of life-threatening or debilitating autoimmune diseases based upon complement immunotherapy through the inhibition of the complement system at the level of C3. Apellis is the first company to advance chronic therapy with a C3 inhibitor into clinical trials. For additional information about Apellis and APL-2, please visit http://www.apellis.com.
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