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.
As Aviceda’s lead investigational candidate, AVD-104 is a glyco-immune therapeutic (GIT) and sialic acid-coated nanoparticle designed using the company's proprietary HALO nanotechnology platform to target a specific area of the innate immune response relating to AMD.
The goal: to potentially prevent dysregulated activity and activate cellular machinery within retinal tissue back into a reparative state.
Talk about this platform.
The High-Affinity Ligands of Sigelcs (HALO) platform incorporates glycobiology (the study of saccharides' structure, biology, and evolution) to modulate the innate immune system in order to develop immuno-oncology-focused therapeutics.
Gotcha. So what makes AVD-104 unique to 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.
In essence: The therapeutic’s dual mechanism of action “ resolves both macrophage/microglial- and complement-mediated inflammation,” according to Mohamed Genead, MD, Aviceda co-founder and CEO.
And its current clinical status?
Aviceda’s investigational new drug (IND) application for AVD-104 was cleared in April 2023, enabling the company to launch the phase 2 SIGLEC trial.
Along with this, Aviceda also submitted a Fast Track Designation application for AVD-104.
Now the SIGLEC study.
A total of 210 patients (aged 55+) have been enrolled in the phase 2 study(NCT05839041) since launching in June 2023.
The trial is divided into two parts:
- Part 1 Multicenter, open-label safety and dose escalation (experimental)
- Part 2 Multicenter, double-masked, randomized (active comparator)
Details on part 1, please.
In Part 1, 30 participants receive a single intravitreal injection of AVD-104 at one of three escalating doses and are then followed for a 3-month safety observation period.
Participants also 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.
And the primary outcome?
The 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.
Any secondary outcomes?
Nope, not for part 1.
Now, didn’t Aviceda already release data from this study?
Indeed they did. Back in October 2023, the company presented positive data on AVD-104 during the EURETINA congress that was based on the first three months of the trial (part 1). Click that link (above) to read our coverage.
So what’s the latest update?
According to Aviceda, 30 participants completed the trial, with all patients tolerating the single dosage of AVD-104 and no drug-related ocular or systemic adverse reaction reported.
How did GA lesion progression perform?
There was a greater reduction in GA lesion progression observed for 3 months when compared to “historical standard-of-care outcomes,” the company stated.
And BCVA changes?
Following a single AVD-104 injection, investigators noted significant BCVA gains that were sustained by the end of the 3-month period.
What else?
Aviceda also reported that the junctional zone hypoautofluorescence—”an imaging biomarker of rapid disease progression”—was:
- Independently graded from fundus autofluorescence imaging
- Notably decreased in eyes receiving AVD-104 doses during the study period
Expert feedback on these results?
Aviceda’s CMO and Senior Vice President David Callanan, MD, expressed the company’s enthusiasm over the latest data.
“We are excited to see signs of significant visual & 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,”he stated.
So what’s next?
Part 2 of the trial is expected to enroll an estimated 300 patients who will be dosed for up to 12 months.
Participants will be divided into three dose groups:
- High dose of AVD-104 (n = 82)Bimonthly injections for the first 12 months, followed by monthly injections 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 of AVD-104 (n = 82)Monthly injections for all 24 months.
- Sham (avacincaptad pegol) (n = 82)Monthly injections for all 24 months.
- Active comparator (2 mg avacincaptad pegol) (n = 41)Monthly injections for all 24 months.
And what’s being measured?
The primary outcome is rate of change in GA area at month 12, as measured by fundus autofluorescence (FAF).
Secondary outcomes include change from baseline in best-corrected visual acuity (BCVA) at month 12, as assessed with the Early Treatment of Diabetic Retinopathy Study (ETDRS) VA.
When can we expect new data?
Per Clinical Trials, the phase 2/3 study is slated for completion by July 2026, so we’ve likely got some time before topline data may be released.
And the bigger picture of this potential therapy?
While AVD-104 wouldn’t potentially become the first (or even second) FDA-approved GA therapy, it does have the opportunity to be the first GA therapy to target key upstream pathways that include macrophage inhibition and complement cascade amplification.