Author: Jeffrey Heier (United States)
Avacincaptad pegol, a polyethylene glycol-conjugated oligonucleotide, is a potent C5 inhibitor delivered via a 100 µl intravitreal injection. The 18-month results of GATHER1, a prospective, randomized, double-masked, multi-national, sham-controlled clinical trial evaluating avacincaptad pegol for the treatment of GA secondary to AMD, are reported here.
This study was a Phase 2/3 trial completed at 63 sites in the United States, Europe, and Israel.
Patients were randomized to avacincaptad pegol 1 mg, avacincaptad pegol 2 mg, avacincaptad pegol 4 mg or sham injection. In part 1, subjects were randomized to receive either 1 mg or 2 mg avacincaptad pegol or sham intravitreal (IVT) injections. In part 2, subjects received either 2 mg or 4 mg avacincaptad pegol or sham IVT injections. GA progression was evaluated as the change in lesion area as measured by fundus autofluorescence (FAF). Square-root transformation was applied to mitigate the impact of baseline factors on GA growth. Other assessments included visual function (best corrected visual acuity and low-luminance visual acuity) and safety.
A total of 286 subjects were enrolled in this study. The pre-specified primary efficacy endpoint was the mean rate of change in GA over 12 months, measured by FAF. The reduction in the mean rate of GA growth (square root transformation) over 12 months was 27.4% (P = 0.0072) for the avacincaptad pegol 2 mg cohort and 27.8%(P = 0.0051) for the avacincaptad pegol 4 mg cohort, both statistically significant, compared with the corresponding sham cohorts. This is the first study in this patient population to have data to 18 months. These data are descriptive in nature. The least-squares mean change from baseline to month 18 in square-root GA lesion area was 0.599 mm in sham-treated subjects vs 0.430 mm in avacincaptad pegol 2 mg-treated subjects (28% reduction; P < 0.0014). The least-squares mean change from baseline to month 18 in square-root GA lesion area was 0.559 mm in sham-treated subjects vs 0.391 mm in avacincaptad pegol 4 mg-treated subjects (30% reduction; P < 0.0021). There were no significant differences in best corrected visual acuity or low-luminance visual acuity between avacincaptad pegol and sham-treated subjects. Avacincaptad pegol was generally well tolerated after 18 months of administration, with no trial discontinuations.
Intravitreal avacincaptad pegol resulted in a statistically significant decrease in the rate of GA lesion growth over 18 months of treatment versus sham injection. GATHER2, a second pivotal clinical trial comparing avacincaptad 2 mg versus sham, has been initiated and is currently enrolling subjects.
Consultant (4DMT, Adverum, Aerie, Aerpio, Aldeyra, Allegro, Alzheon, Annexon, Apellis, Aprea, Asclepix, Aviceda, BVT, Dark Horse, DTx, Eloxx, Galimedix, Genentech, Graybug, Gyroscope, Iveric, jCyte, Kanghong, LensGen, NGM, Novartis, Ocular Therapeutix, OcuTerra, Oxurion, Palatin, Regeneron, Regenxbio, Stealth, Thea, Verseon, Vinci, Voyant) Research grants (Apellis, Asclepix, Bayer, Genentech, Graybug, Gyroscope, Hemera, Iveric, Kanghong, Kodiak, NGM, Notal Vision, Novartis, Regeneron, Regenxbio, Stealth)