Apellis Pharmaceuticals‘ plans to begin the Phase III trial of its complement C3 inhibitor candidate APL-2 for treatment of geographic atrophy received a boost last week when it was announced that 18-month Phase II results confirmed the previously reported 12-month results: that treatment sustained the effect of slowing the growth of geographic atrophy (GA) lesions.
Rishi Singh, MD, staff surgeon at the Cole Eye Institute of the Cleveland Clinic, reported the updated FILLY trial results last week at the Macula Society meeting in Beverly Hills, CA. “APL-2, when given monthly or even every other month, demonstrated statistically significant differences in GA growth over 18 months as compared to placebo patients despite no treatment for six months,” Dr. Singh says.
The Phase II FILLY trial involved three dosing groups: the sham group (n=81); and two active groups that received APL-2 injections either every other month (n=79) or monthly (n=86) for 12 months. From month 12 to 18, subjects received no injections. At 18 months, imaging showed a continued effect of APL-2 to slow lesion growth, with a 16.3% reduction with every-other-month treatments and 20.4% reduction with monthly injections compared to the sham group. Mean lesion size at 18 months was 0.49 mm2 for the sham, 0.41 mm2 for every other month, and 0.39 mm2 for the monthly group. At 12 months, mean lesion size was 0.34 mm2 for sham, 0.28 mm2 for every other month, and 0.26 mm2 for monthly.
In terms of visual outcomes, Dr. Singh reports that the differences between groups were not statistically significant at 18 months: losses of 6.4 letters for sham, 8.8 letters for every other month, and 7.7 letters for monthly treatment. “Upon discontinuation of APL-2 at month 12, the treatment effect declines,” he says.
Dr. Singh notes that 21% of the every-other-month treatment group had new onset exudation at 18 months versus 9% for the monthly group and 1% for sham. Otherwise, the safety profile was similar across all three treatment groups.
He offers three possible explanations for the exudation associated with APL-2: the agent induces a vascular epithelial growth factor (VEGF)-like effect in the absence of new blood vessel growth (neovascularization); APL-2 induces neovascularization and exudation; or APL-2 induces exudation for neovascularization that existed before treatment but was undetected.
“The risk/benefit profile at 18 months supports the decision to move to Phase III testing,” says Dr. Singh.
Apellis previously announced that, following discussions with FDA in December, it has finalized the Phase III protocol for APL-2 for treatment of GA. Phase III, 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 III trials will be similar in design to the Phase II FILLY trial, including the eligibility criteria and primary endpoint of GA lesion growth at 12 months. Patients whose treatment eye develops exudative age-related macular degeneration (AMD) will continue to be treated with APL-2 along with VEGF inhibitors, the current standard of care for exudative AMD.
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