Aviceda Therapeutics has commenced Part 2 of the Phase II/III SIGLEC trial, assessing AVD-104 for geographic atrophy (GA) resulting from age-related macular degeneration (AMD). The first subject has been dosed in this double-masked, multicenter, randomized, controlled trial, which will compare AVD-104 with avacincaptad pegol over a 12-month period, with an option for an additional 12-month extension.
Advancing AVD-104 for GA Treatment
David Callanan, MD, Aviceda’s chief medical officer and senior vice president, stated that the rapid initiation of Part 2, including site activation and enrollment, was based on the efficacy and safety observed in Part 1, suggesting AVD-104 as a potentially disease-modifying treatment. Part 1 of SIGLEC indicated a positive safety profile for AVD-104, with GA patients showing improvements in best-corrected visual acuity (BCVA) at 3 months.
The trial will evaluate the efficacy and safety of AVD-104 against avacincaptad pegol in treating GA. Participants will receive either a low or high dose of AVD-104 or the active comparator. The primary endpoint is the variation in the growth rate of the GA area at 12 months, measured by fundus autofluorescence.
AVD-104's Novel Dual Mechanism
According to Mohamed Genead, MD, cofounder and CEO of Aviceda, current GA treatments only address complement dysregulation. AVD-104, however, targets both macrophage/microglial-mediated inflammation and the complement pathway. Genead suggests that if this dual-mechanism approach proves safe and effective, it could lead to a paradigm shift in GA treatment.
Trial Design and Previous Findings
Part 2 of the SIGLEC trial is designed as a multi-center, double-masked, randomized, controlled study to assess the safety and efficacy of AVD-104 and avacincaptad pegol for GA secondary to AMD. Patients will be dosed for 12 months, with an option to continue for another 12 months. Participants will receive either low-dose AVD-104, high-dose AVD-104, or the active comparator. The primary endpoint will measure the difference in growth rate of the GA area in patients treated with AVD-104 versus those receiving the active comparator at 12 months, as measured by fundus autofluorescence. The trial will also explore and compare numerous other visual functional and anatomic efficacy measures between AVD-104 and the active comparator.
Part 1 of the SIGLEC trial was a multi-center, open-label safety and dose-escalation trial involving 30 patients who received a single intravitreal injection of AVD-104 and were followed for 3 months. All patients tolerated the single dose of AVD-104 at month 3, with no drug-related ocular or systemic severe adverse reactions observed.
Preclinical and Clinical Evidence
Aviceda reports that AVD-104 has demonstrated robust in-vitro/vivo efficacy, inhibiting both inflammatory and complement pathways, with potential for every 4-6 month dosing. AVD-104 has also shown anti-neovascular activity equivalent to aflibercept (Eylea) in an ocular CNV model.
Earlier in the year, Aviceda announced positive topline data from Part 1 of the Phase 2/3 SIGLEC trial, showing positive safety and efficacy outcomes observed 3 months after a single dose of AVD-104. Callanan noted the company was pleased to see signs of significant visual and functional improvement and rapid reduction in the rate of GA lesion growth with a positive overall safety profile following a single dose of AVD-104.
