Annexon Eyes Q4 2026 Phase III Readout for Vision-Preserving GA Drug

Annexon NASDAQ: ANNX said it expects to report the month-15 primary-endpoint analysis from its Phase III ARCHER II trial of vonaprument in geographic atrophy, or GA, during the fourth quarter of 2026. The company is testing the C1q-targeting treatment with vision preservation, rather than lesion growth, as its primary efficacy focus.

Chief Executive Officer Douglas Love said ARCHER II was designed to replicate functional findings from the company’s Phase II ARCHER study. The Phase III trial enrolled 659 patients, randomized 2-to-1 between active treatment and sham, and evaluates confirmed loss of 15 letters of best-corrected visual acuity at both month 15 and month 24.

“ARCHER II is a highly differentiated Phase III study with vision as the primary endpoint,” Love said, adding that the study is larger, longer and more highly powered than the Phase II trial.

Focus on Vision Loss in Geographic Atrophy

Geographic atrophy is an advanced form of dry age-related macular degeneration that can lead to irreversible vision loss. Retina specialist Roger Goldberg of Bay Area Retina Associates said existing FDA-approved GA therapies, SYFORVE and IZERVAY, have demonstrated an ability to slow lesion growth but have not established vision preservation in their pivotal studies.

Goldberg said patients are primarily concerned with functional consequences of the disease, including recognizing faces, driving, reading and maintaining independence, rather than changes in lesion size. He cited an estimated 1.5 million people with GA in the U.S., more than 2.5 million in Europe and over 8 million globally.

According to Goldberg, only about 10% of U.S. GA patients are currently treated, in part because of the absence of demonstrated functional benefit from available therapies and safety considerations. He said a treatment that can reduce the risk of meaningful vision loss could change discussions between clinicians and patients and potentially support treatment adherence.

Phase II Data and Mechanistic Rationale

Annexon’s vonaprument is designed to inhibit C1q, a component of the classical complement pathway that the company says contributes to neuroinflammation and the loss of neuronal synapses. In GA, the company’s strategy is to protect retinal photoreceptors and synapses, which are central to visual acuity.

Lloyd Clark, Annexon’s senior vice president of ophthalmology strategy and innovation, said the Phase II ARCHER study showed a 27% reduction in ellipsoid-zone loss across the macula compared with sham. The ellipsoid zone, measured by optical coherence tomography, is used as an indicator of photoreceptor health.

Clark also highlighted Phase II data showing a dose-dependent effect on confirmed 15-letter vision-loss events. In the monthly-treatment group, the company reported a 73% reduction in the risk of clinically significant vision loss relative to sham.

In subgroup analyses discussed during the event, patients with foveal retinal pigment epithelium atrophy had confirmed 15-letter loss rates of 25% in the sham arm and 5.9% in the monthly-treatment arm. Clark said the trial also showed differences in patient groups defined by low-luminance visual deficit, a measure associated with photoreceptor function.

The company noted that the final six months of the Phase II study involved off-treatment follow-up. Clark said vision loss resumed at similar rates in all groups during that period, without treated eyes “catching up,” which he characterized as evidence consistent with a disease-modifying effect.

ARCHER II Design, Readout and Regulatory Plan

The company completed enrollment two months ahead of schedule and enrolled 30 more patients than planned. It said discontinuation rates through the first 12 months were in the mid-single digits, below the roughly 15% discontinuation rate reported in its Phase II study.

ARCHER II excludes patients with visual acuity worse than 20/100, a population Clark said has limited remaining vision to lose under the trial’s endpoint. Annexon said the Phase III population otherwise closely resembles the Phase II cohort, including the proportions of patients with foveal disease and lower low-luminance visual deficit.

Annexon plans to first conduct a single analysis across all 659 patients and announce either a positive result or continued masking in the fourth quarter of 2026. If the total analysis is positive, the company expects to conduct two pre-specified sub-analyses and announce those results in the first quarter of 2027.

• A positive total-study analysis would support the company’s proposed European regulatory pathway.
• Positive results across the total analysis and both sub-analyses would lead Annexon to unmask the study, provide detailed data and prepare regulatory filings.
• If any analysis is not positive, the study would remain masked through month 24 to preserve the integrity of the later endpoint.

Love said Annexon has FDA Fast Track designation in the U.S. and PRIME designation in Europe for the program. The company said it is aligned with European regulators on a single-study approval approach, while the FDA requested pre-specified sub-analyses intended to satisfy the agency’s convention of two studies.

Commercial Positioning

Love said Annexon intends to position vonaprument as a potential replacement for currently approved therapies and as a driver of broader GA treatment adoption if the trial is successful. He said the company believes bilateral disease could expand the commercial opportunity beyond patient counts alone.

Goldberg said local intravitreal treatment may be more familiar to retina specialists than systemic therapies, particularly because of potential systemic safety and management considerations in an older patient population. He added that, if approved, vonaprument would likely be most relevant for patients with remaining functional vision to preserve rather than those with either very advanced disease or very early, asymptomatic lesions.

Annexon also said it has expanded its ophthalmology organization, including the return of Dr. Don Fong to lead ophthalmology clinical development and the appointment of Jake Schumacher to lead the ophthalmology franchise.

About Annexon (NASDAQ:ANNX)

Annexon, Inc NASDAQ: ANNX is a clinical-stage biotechnology company developing therapies for diseases associated with abnormal activation of the classical complement pathway. The company's approach is designed to selectively inhibit complement activity while preserving the immune system's ability to perform essential functions.

Annexon's pipeline has included ANX005, a monoclonal antibody targeting C1q, the initiating protein of the classical complement pathway. The company has evaluated ANX005 in immune-mediated and neuroinflammatory disorders, including Guillain-Barré syndrome.

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