Annexon provides update on ARCHER II global registrational program in geographic atrophy

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Annexon Inc announced patient dosing was initiated in the global pivotal Phase 3 ARCHER II trial evaluating ANX007 for the treatment of geographic atrophy (GA), the only GA pivotal program utilizing visual protection as the global regulatory-aligned primary endpoint.

In a news release, the company also announced new data regarding protection of vision and vision-related retinal structure from the Phase 2 ARCHER trial, supporting the disease-modifying potential of ANX007 for the treatment of GA.

These data were recently presented at the American Society of Retina Specialists (ASRS) Annual Scientific meeting.

GA is a chronic, progressive neurodegenerative disease that is the leading cause of blindness for over 8 million elderly people worldwide, resulting in the loss of independence and major disruption in their daily lives. Although there are 2 currently FDA-approved treatments to slow disease progression in GA, there are currently no approved treatments indicated to protect vision in GA.¹

Douglas Love, president and CEO of Annexon, pointed out that ANX007 is the only investigational medicine for GA to date to show in a randomized clinical trial significant protection of both visual acuity and key visual structures in regions of the eye essential for vision.

“These data underscore ANX007’s potential best-in-class profile and make all the more exciting the initiation of the ARCHER II global, pivotal Phase 3 study designed to treat patients impacted by this devastating disease at a vulnerable stage in their lives,” Love said in the news release. “Assuming success in the ARCHER II trial, ANX007 has the potential to be the first GA therapy approved to protect vision.”

According to the company’s news release, ARCHER II is a global, randomized, sham-controlled Phase 3 trial with topline data expected in the second half of 2026. The ANX007 registrational program has received regulatory alignment with both the FDA and the European Medicines Agency (EMA) on key study elements, including on using, for the first-time in GA, best corrected visual acuity (BCVA) protection against ≥15-letter loss as the primary outcome measure (equivalent to 3 lines on a standardized eye chart).

In ARCHER II, ANX007 will be compared to sham control in a well-powered study with a robust safety database that is expected to enroll approximately 630 patients. ANX007 is the only therapeutic candidate for GA to date to receive Priority Medicine (PRIME) designation in the European Union, and has been granted Fast Track designation from the FDA.

Eleonora Lad, MD, PhD, vice chair of Clinical Research at Duke Eye Center added that treatments for GA have primarily focused on addressing lesion growth by measuring protection of the retinal pigment epithelium (RPE), supportive cells that do not detect light across the retina.

“Unfortunately, current treatments have not translated to protection of clinically meaningful vision for patients,” she said in the news release. “The new analyses of the Phase 2 ARCHER trial are very encouraging, demonstrating protection of photoreceptors in the central fovea, the region of the retina needed for important activities such as reading, driving and seeing faces. These data shed new insights into the mechanism of ANX007 to potentially modify disease activity, leading to protection of vision loss in GA.”

Data highlights from the ARCHER Phase 2 analyses

ANX007 provided broad-based protection of vision vs. sham-treated eyes

• Statistically significant and dose dependent protection of vision measured by best corrected visual acuity (BCVA) protection against ≥15-letter loss at month 12, which represents three lines on the standard Early Treatment of Diabetic Retinopathy Study (ETDRS) eye chart and is a widely accepted clinically meaningful assessment of visual acuity (21.3% (sham) vs. 5.6% (ANX007 monthly); p = 0.0021)
• Statistically significant protection of vision in low light conditions, low luminance visual acuity (LLVA) at month 12, which is an important assessment of visual performance for everyday activity (LLVA ≥15-letter loss at month 12: 20.3% (sham) vs. 7.6% (ANX007 monthly); p = 0.022)

ANX007 provided structural protection in regions of the retina critical for visual acuity

• Photoreceptors are neurons in the retina responsible for detecting light, and thus protecting their structure is essential for protecting vision
• ANX007 provided up to 60% protection of photoreceptors compared to sham within the central 1.5 mm of the fovea, as measured by ellipsoid zone (EZ) through 12 months (p = 0.0319*)
• ANX007 provided 29% protection of photoreceptors across the full retinal field as measured by EZ through 12 months (p = 0.017*)
• ANX007 demonstrated a trend of protection against RPE loss in the central foveal subfield, the region where RPE loss best correlates with vision loss (18% protection of RPE loss, p = 0.40*). RPE loss is a measure that lags behind photoreceptor loss.

*nominal p-value

Moreover, the company noted that data indicate intravitreal administration of ANX007 fully stops C1q and activation of its inflammatory pathway. In the Phase 2 ARCHER trial, ANX007 was shown to preserve vision on multiple measures and provided significant structural protection within the retina, particularly of photoreceptors in the central fovea that are important to visual acuity.

Additionally, ANX007 was generally well-tolerated through month 12, with no increase in choroidal neovascularization (CNV) rates between the treated and sham arms and no events of retinal vasculitis reported. ANX007 has been granted Fast Track designation from the FDA and is the first therapeutic candidate for the treatment of GA to receive Priority Medicine (PRIME) designation in the European Union, which provides early and proactive support to developers of promising medicines that may offer a major therapeutic advantage over existing treatments or benefit to patients without treatment options.¹

Annexon is now planning to initiate a global pivotal Phase 3 ARCHER II trial in mid-2024, with a pivotal Phase 3 head-to-head ARROW trial against a pegcetacoplan injection, or SYFOVRE, planned in the second half of 2024. The trials are designed to confirm these Phase 2 ARCHER findings, specifically the protection ANX007 provides against vision loss.²

Plans for an injection-controlled study, ARROW, to assess the prevention of ≥15-letter loss of BCVA, are also ongoing.

Reference:

1. Annexon Biosciences. Annexon Provides Update on ARCHER II Global Registrational Program in Geographic Atrophy. GlobeNewswire News Room. Published August 5, 2024. Accessed August 5, 2024. https://www.globenewswire.com/news-release/2024/08/05/2924242/0/en/Annexon-Provides-Update-on-ARCHER-II-Global-Registrational-Program-in-Geographic-Atrophy.html

2. Annexon presents new neuroprotection data showing ANX007 protects vision and vision-associated structures in geographic atrophy at ARVO 2024 annual meeting. News release. Annexon. May 7, 2024. Accessed May 8, 2024. https://ir.annexonbio.com/news-releases/news-release-details/annexon-presents-new-neuroprotection-data-showing-anx007