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Annexon releases topline data for phase 2 GA study

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Annexon, Inc. released topline data from the phase 2 ARCHER trial assessing ANX007 for the treatment of geographic atrophy (GA).

Give me some company background.

Based in Brisbane, California, Annexon is a clinical-stage biopharmaceutical company that is developing and advancing a new class of complement medicines to target inflammation in autoimmune, neurodegenerative, and ophthalmic diseases.

Go on …

Annexon’s focus lies in the complement pathway and its discovery of C1q, an initiator of the classical complement pathway in the immune system that is responsible for removing functional synapses in disease—leading to photoreceptor cell loss (GA).

The company previously found that blocking C1q actually protects photoreceptor cell synapses and cell function.

Now talk about ANX007.

ANX007 is a clinical-stage investigational monoclonal antibody antigen-binding fragment (Fab) formulated to be intravitreally administered.

The proposed mechanism of action includes a differentiated neuroprotective approach that is designed to protect photoreceptor cells and retinal function by blocking C1q and the entire classical complement pathway,

Now talk about this trial.

The randomized, multicenter, parallel-group, double-masked, 4-arm, sham-controlled phase 2 ARCHER trial (NCT04656561) enrolled 270 patients (ages 50+; average age of 80) stratified by GA lesion size, location, and choroidal neovascularization (CNV) in the fellow eye at enrollment.

To note, patients were nearly equally split between foveal (49.4%) and non-foveal (57.3%) groups, with 96% of candidates that were enrolled from the United States.

And the dosages?

Patients were randomly assigned to receive 5 mg ANX007 on a monthly basis (n = 89); the same dosage of ANX007 every other month (n = 92); or a sham dosage monthly or every other month (pooled n = 89) for 12 months.

A 6-month off-treatment period followed.

What was measured?

The primary outcome included rate of change in GA lesion growth from baseline (measured by fundus autofluorescence [FAF]) in the study eye for 12 months.

Any pre-specified measures?

Yup! They include changes from baseline in:

  • Best-corrected visual acuity (BCVA)
  • Low-luminance BCVA
  • Low-luminance visual acuity (VA) deficit

Findings?

Patients receiving monthly ANX007 exhibited: a 72% reduction in risk of >15-letter vision loss (p=0.006), while those receiving ANX007 every-other-month treatment showed a 48% reduction in risk of >15-letter vision loss (p=0.064); and a 59% reduction in risk of >15-letter loss (p=0.008) was noted for the pooled treatment group.

Subsequently, patients treated monthly and every-other-month with ANX007 might have less measurable vision loss.

According to Annexon, “changes from baseline is a widely accepted functional endpoint of [BCVA].

What about the primary endpoints?

Statistical significance was not reached for the mean rate of change in GA lesion area (versus sham) at 12 months:

  • Monthly ANX007 group = 6.2% reduction (p = 0.526)
  • Every-other-month ANX007 group = 1.3% reduction (p = 0.896)
  • Pooled group = 3.7% reduction (p = 0.673)

See here for additional data.

Any adverse events?

For ANX007-treated patients, three serious adverse events (SAEs) of endophthalmitis were noted (related to the injection procedure and not the actual treatment).

Further, three SAEs of intraocular inflammation (treatment-related) and one SAE of retinal artery occlusion (treatment-related) were observed.

The study authors noted that none of the four SAEs were related to retinal vasculitis.

What about the follow-up period?

The 6-month off-treatment data is still ongoing; results will be reported along with the final data report after the study’s completion.

Significance?

According to Annexon, the data is the first demonstration that a complement-based therapy can protect against vision loss (GA) in a 12-month trial.

So what’s next?

According to Annexon CEO Douglas Love, “Protecting against vision loss for patients with GA is the ultimate clinical goal.”

He further stated, “Based on the ARCHER trial results, we plan to engage with regulators to determine the optimal path forward to bring ANX007 to patients as expeditiously as possible.”