Additional SOL-1 analyses show delayed CSFT worsening with AXPAXLI

New 52-week analyses from the phase 3 SOL-1 trial suggest that the investigational intravitreal therapy AXPAXLI (OTX-TKI) may offer extended durability and sustained anatomic control in patients with neovascular (wet) age-related macular degeneration (AMD), a finding that could have implications for treatment burden in this chronic disease.

The data, presented at the 14th Annual Vit-Buckle Society meeting, expand on previously reported topline results and include post hoc analyses evaluating central subfield thickness (CSFT) progression and visual outcomes. While the primary endpoint of the superiority trial—maintenance of visual acuity at week 36—has already been reported as positive, these additional analyses focus on durability metrics that are increasingly relevant in retina practice.

Trial design and key findings

SOL-1 (NCT06223958) is a randomized, double-masked, active-controlled phase 3 trial evaluating a single intravitreal dose of AXPAXLI (0.45 mg) compared with aflibercept (2 mg) following a standardized loading phase. The study enrolled 344 treatment-naïve patients with wet AMD across more than 100 sites in the United States and Argentina.

The trial met its primary endpoint, with 74.1% of patients in the AXPAXLI arm maintaining vision (defined as <15-letter loss in best-corrected visual acuity [BCVA]) at week 36, compared with the aflibercept arm (risk difference, 17.5%; P = .0006). At week 52, 65.9% of AXPAXLI-treated patients maintained vision, corresponding to a 21.1% risk difference versus aflibercept (P < .0001).

Post hoc analyses presented at the meeting focused on time to anatomic worsening. From week 8 onward, median time to a ≥30 µm increase in CSFT was 39 weeks in the AXPAXLI group versus 16 weeks with aflibercept (hazard ratio [HR], 0.7; descriptive P = .0028). For a ≥75 µm increase, median time was 46 weeks versus 24 weeks, respectively (HR, 0.5; descriptive P < .0001). These findings suggest a lower risk of recurrent disease activity over time with AXPAXLI, although the analyses were not prespecified.

Visual acuity outcomes appeared broadly consistent with prior anti-VEGF studies, with greater gains observed in patients with worse baseline vision. In the lowest BCVA quartile, mean improvement reached +11.8 ETDRS letters at week 52 with AXPAXLI versus +8.5 letters with aflibercept. Patients with near-normal baseline vision demonstrated minimal change, reflecting a ceiling effect commonly observed in AMD trials.¹

Notably, a high proportion of patients remained free of rescue therapy: 81% at week 24, 75% at week 36, and 66% at week 52. Among these patients, visual gains achieved during the loading phase were largely maintained.

Safety profile

The safety findings reported to date appear consistent with the known profile of intravitreal therapies. No cases of endophthalmitis or retinal vasculitis were reported in the trial. Vitreous floaters, attributed to the hydrogel delivery system, were observed but resolved over time (mean ~20 weeks) and did not appear to adversely affect vision.

However, longer-term safety data, including outcomes through week 104, remain pending and will be important in assessing the full risk profile.

Clinical context

Wet AMD remains a leading cause of irreversible vision loss in older adults, driven by pathologic angiogenesis mediated largely by vascular endothelial growth factor (VEGF).² Current standard-of-care therapies—including aflibercept, ranibizumab, and faricimab—require frequent intravitreal injections, often every 4 to 8 weeks, although extended dosing intervals are possible in some patients.³

Treatment burden remains a major challenge in real-world settings, where undertreatment is associated with worse visual outcomes.⁴ As such, durable therapies capable of maintaining disease control with fewer injections represent a key unmet need.

Mechanism and drug background

AXPAXLI is a bioresorbable intravitreal hydrogel formulation delivering axitinib, a multi-target tyrosine kinase inhibitor with anti-angiogenic activity. Unlike monoclonal antibody–based anti-VEGF therapies, axitinib inhibits multiple receptor pathways involved in angiogenesis, including VEGF receptors.⁵ The hydrogel platform is designed for sustained drug release over several months, potentially reducing injection frequency.

Axitinib is currently approved in systemic oncology indications, but its intravitreal use remains investigational.⁶

Interpretation and limitations

The SOL-1 findings suggest that AXPAXLI may offer extended durability compared with aflibercept, particularly in terms of anatomic stability and reduced need for rescue therapy. However, several caveats warrant consideration.

First, many of the durability findings are derived from post hoc analyses and should be interpreted as hypothesis-generating. Second, the trial design includes a loading phase with aflibercept prior to randomization, which may influence early outcomes and complicate comparisons with real-world treatment patterns. Third, head-to-head comparisons with newer agents such as faricimab are not available.

Additionally, while the sponsor has indicated plans to pursue regulatory approval based on a single pivotal trial, this approach remains under evolving regulatory guidance and may require further validation.

Next steps

Patients in SOL-1 will continue to be followed through week 104 to assess long-term safety and durability. Regulatory discussions with the US Food and Drug Administration are ongoing regarding a potential new drug application.

Further confirmatory studies and real-world data will likely be necessary to establish the role of AXPAXLI within the treatment landscape.

References

1. Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006;355(14):1432-1444. https://www.nejm.org/doi/full/10.1056/NEJMoa062655

2. Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration. Lancet Glob Health. 2014;2(2):e106-e116. https://doi.org/10.1016/S2214-109X(13)70145-1

3. Heier JS, Khanani AM, Quezada Ruiz C, et al. Efficacy, durability, and safety of faricimab in neovascular AMD (TENAYA and LUCERNE). Lancet. 2022;399(10326):729-740. https://doi.org/10.1016/S0140-6736(22)00018-6

4. Holz FG, Tadayoni R, Beatty S, et al. Multi-country real-life experience of anti-VEGF therapy for wet AMD. Br J Ophthalmol. 2015;99(2):220-226. https://bjo.bmj.com/content/99/2/220

5. Hu-Lowe DD, Zou HY, Grazzini ML, et al. Nonclinical antiangiogenesis and antitumor activities of axitinib. Mol Cancer Ther. 2008;7(3):665-674. https://aacrjournals.org/mct/article/7/3/665/93366

6. US Food and Drug Administration. Axitinib (INLYTA) prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202324lbl.pdf

7. ClinicalTrials.gov. A study to evaluate OTX-TKI (AXPAXLI) in subjects with wet AMD (SOL-1). https://clinicaltrials.gov/study/NCT06223958