Aviceda Therapeutics announced positive data from an ongoing phase 2/3 clinical data on AVD-104 for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
Refresh me on AVD-104.
AVD-104 is glyco-immune therapeutic (GIT) and sialic acid-coated nanoparticle that targets a specific area of the innate immune response relating to AMD.
The goal: Potentially prevent dysregulated activity and activate cellular machinery within retinal tissue back into a reparative state.
How is this different from other GA treatments?
Unlike previous treatments which attempt to shutdown humoral components of the innate immune response in order to target AMD, AVD-104 focuses on the cellular and humoral aspects of inflammatory processes within AMD leveraging an effective and well-tolerated delivery system.
Anything else to know before we talk clinical data?
You betcha there is.
Back in April 2023, the FDA cleared Aviceda’s investigational new drug (IND) application for AVD-104, enabling the company to launch a phase 2 trial (more on that in a moment).
Also of note: per the FDA’s request, Aviceda submitted a Fast Track Designation application for AVD-104 in March 2023 (coverage here).
Now talk about this phase 2 trial.
Launched in June 2023, the phase 2 SIGLEC trial (NCT05839041) has enrolled 210 patients (ages 55 and older) and is divided into two parts:
- Part 1 → Multicenter, open-label safety and dose escalation (experimental)
- Part 2 → Multicenter, double-masked, randomized (active comparator)
Give me more on these two parts.
Part 1 includes 24 participants receiving a single intravitreal injection of AVD-104 at one of three escalating doses. Additionally, all patients will be followed for 3 months for safety observation.
Participants will have the opportunity to receive high-dose monthly injections of AVD-104 (and be followed for safety), but only once 50% of patients in part 2 of the study reach the 6-month mark.
Part 2 includes three groups: Low-dose AVD-104 (n = 70), high-dose AVD-104 (n = 70), and sham injections (n = 70).
- High dose → Monthly injections for the first 12 months. For months 13-24, 50% of the group will be randomized to every-other-month (EOM) injections, while 50% will continue monthly injections.
- Low dose → Monthly injections for all 24 months.
- Sham → Monthly injections for all 24 months.
What’s being measured?
Two primary outcomes:
- Part 1 → Number of patients who experience a dose-limiting toxicity corresponding to a category of 3 or greater (on the National Cancer Institute Common Terminology Criteria for Adverse Events) for a 3-month period.
- Part 2 → Rate of change in GA area at month 12, as measured by fundus autofluorescence (FAF).
- Secondary outcome: change from baseline in best-corrected visual acuity (BCVA) at month 12, as assessed with the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity.
Gotcha. So which part is this new data from?
The first 3 months of phase 1.
Now what’s the new data saying?
Per Aviceda, the data indicates continued safety for AVD-104, with no drug-related adverse events (AEs) or serious AEs (so far, that is):
- 3 months (cohorts 1 and 2)
- 2 months (cohort 3)
- 1 month (cohort 4)
Further, there have been no evidence of any significant dose-limiting toxicity and no reports of:
- Drug-related ocular inflammation
- Retinal vasculitis
- Choroidal neovascularization
- Infection
- Optic nerve abnormalities
When can we expect new data?
Per Clinical Trials, the phase 2 study is slated for completion by July 2026… updated data will likely be released in 2024.
Significance?
AVD-104 has the potential to be the first GA therapy to target key upstream pathways including macrophage inhibition and complement cascade amplification.
These findings, “Modulation of Macrophages and Complement Dysfunction in Nonexudative AMD utilizing Novel Sialic-acid Coated Nanoparticles,” were presented by Baruch Kuppermann, MD, chair of the Department of Ophthalmology at University of California Irvine, director of the Gavin Herbert Eye Institute, and the Roger F. Steinert Endowed Chair in Ophthalmology, during the 23rd EURETINA Congress held in Amsterdam, Netherlands, from October 4–7, 2023.