Annexon, Inc. announced new phase 2 data and phase 3 developments from its ARCHER clinical program evaluating ANX007 for the treatment of geographic atrophy (GA).
Let’s start with a company refresh.
Annexon is a clinical-stage biopharmaceutical company based in Brisbane, California.
Its focus: Developing and advancing a new class of complement medicines to target inflammation in autoimmune, neurodegenerative, and ophthalmic diseases.
And how is it doing this?
By focusing in on the complement pathway and C1q, an initiator molecule of the classical pathway of the complement system responsible for removing functional synapses in disease, which in turn can lead to photoreceptor cell loss (such as what can occur in GA).
- More about this science: Annexon previously discovered that blocking C1q actually protects photoreceptor cell synapses and cell function.
- Thus: Inhibiting C1q at the start of the complement pathway could also stop downstream inflammation and tissue damage.
And how does this relate back to Annexon?
The company has developed a proprietary platform that works to inhibit this C1q activation via a pipeline of clinical assets targeting diseases within three therapeutic areas:
- Autoimmune (Guillain-Barré Syndrome [GBS])
- Neurodegeneration (Huntington's disease [HD])
- Ophthalmology (GA)
Gotcha. Now talk about this ANX007.
ANX007 is a clinical-stage investigational monoclonal non-pegylated antigen-binding fragment (Fab) antibody formulated to selectively inhibit (block) C1q and the entire complement pathway.
How it does this: By using a differentiated neuroprotective approach that protects photoreceptor cells and retinal function via intravitreal administration.
- Regulatory note: ANX007 has already been granted FDA Fast Track designation and has been given Priority Medicine (PRIME) designation in the European Union (EU).
Now the clinical data.
We’ll start with the company update on that phase 2 ARCHER trial—the first data we’ve reported on since Annexon released 12-month topline data in May 2023.
But first, a study refresh.
- The design: Randomized, multicenter, parallel-group, double-masked, 4-arm, sham-controlled phase 2 trial (NCT04656561)
- The participants: 270 GA patients (aged 50+; average age of 80)
- The dosages:
- 5 mg ANX007 every month (EM)
- 5 mg ANX007 every other month (EOM)
- Sham dosage either EM or EOM
- The duration: 12 months
- Primary outcome measure: rate of change in GA lesion growth from baseline in study eye (at 12 months)
And that topline data?
Statistical significance wasn’t reached for the primary endpoint at 12 months, unfortunately.
However: Patients receiving ANX007 when dosed EM demonstrated a 72% reduction in risk of >15-letter vision loss, while the EOM ANX007 group demonstrated a 48% reduction (compared to 59% in the sham group).
See here for more details.
So what are these latest findings?
Presented during the 42nd annual meeting of the American Society of Retina Specialists (ASRS) in July 2024, the company reported that ANX007 provided broad-based protection of vision vs sham-treated eyes. Specifically: Supporting the primary endpoint: A statistically significant and dose-dependent protection of vision, as measured via BCVA protection against ≥15-letter loss at Month 12.
- 21.3% (sham group) vs 5.6% ( ANX007 EM group); p = 0.0021
Plus: Also at Month 12, ANX007 demonstrated statistically significant protection of vision in low light conditions (low luminance visual acuity [LLVA]), as indicated by LLVA ≥15-letter loss
- 20.3% (sham group) vs. 7.6% (ANX007 EM group); p = 0.022
How did ANX007 perform in structural protection within the retina?
Annexon reported that ANX007 provided up to 60% of protection of photoreceptors vs sham (within the central 1.5 mm of the fovea; [p = 0.0319]) as well as 29% of protection of photoreceptors vs sham (p = 0.017) through Month 12.
Note: These were determined based on measurements by the ellipsoid zone (EZ).
Overall, “ANX007 demonstrated a trend of protection against RPE (retinal pigment epithelium) loss in the central foveal subfield,” the company stated.
- To be exact: 18% protection of RPE loss, p = 0.40
And the significance of this?
The latest findings indicate that ANX007 is the only GA-targeted investigational candidate evaluated in a randomized clinical trial (RCT) to demonstrate “significant protection of both visual acuity and key visual structures in regions of the eye essential for vision,” noted Douglas Love, Annexon president and CEO.
“These data shed new insights into the mechanism of ANX007 to potentially modify disease activity, leading to protection of vision loss in GA,” added Eleonora Lad, MD, PhD, vice chair of Clinical Research at Duke Eye Center and scientific advisor to Annexon.
Sounds promising… now let’s discuss this phase 3 trial.
Here’s what we know:
- The study name: ARCHER II
- The design: Global, randomized, double-masked, sham-controlled trial
- The participants: 630 patients (estimated) diagnosed with GA secondary to age-related macular degeneration (AMD)
- The setup: Randomized 2:1 to receive EM dosing of ANX007 or sham injections
- Study duration: 12 and 18 months from initiation of dosing
- Primary endpoint: Prevention of ≥15-letter loss of BCVA
- Secondary endpoints: Safety, LLVA, and photoreceptor integrity (measured via EZ)
Why are these outcome measures important?
Zeroing in on the primary endpoint, the company noted that patients with a BCVA ≥15-letter loss has previously been established as a functional endpoint for the basis of both FDA and EMA ophthalmic drug approvals.
- For example: SYFOVRE (pegcetacoplan injection; Apellis Pharmaceuticals) and IZERVAY (avacincaptad pegol intravitreal solution, Astellas Pharma US).
As a bonus: Annexon is also planning to initiate an injection-controlled study called ARROW, with the intent to evaluate preventing a BCVA ≥15-letter loss in the near future (no timeline as of now).
Gotcha. And when can we expect data from ARCHER II?
Topline data is expected by H2 2026, according to Annexon.