Ocular Therapeutix enrolls first patient in SOL-X long-term extension trial for AXPAXLI

Ocular Therapeutix has initiated a long-term extension trial evaluating the investigational intravitreal therapy AXPAXLI in patients with neovascular (wet) age-related macular degeneration (AMD), marking a step toward assessing extended durability and safety beyond prior phase 3 studies. The first patient has been enrolled in the SOL-X trial, an open-label extension designed to follow participants from earlier pivotal studies for an additional 3 years.

The development reflects ongoing efforts to address a central challenge in wet AMD management: maintaining consistent vascular endothelial growth factor (VEGF) suppression while reducing treatment burden. Current anti-VEGF therapies, although highly effective, often require frequent intravitreal injections and are associated with real-world undertreatment and suboptimal long-term outcomes.¹,²

Trial overview

SOL-X is a multicenter, 36-month, open-label extension study enrolling patients who have completed 2 years of follow-up in the phase 3 SOL-1 or SOL-R trials. Participants will receive AXPAXLI at fixed 24-week intervals, with scheduled assessments every 12 weeks and additional visits as needed. Supplemental anti-VEGF injections may be administered at investigator discretion.

The primary objective is to evaluate long-term safety. Secondary and exploratory endpoints include visual acuity outcomes, as well as the incidence and progression of fibrosis and macular atrophy—complications increasingly recognized as contributors to vision loss despite anti-VEGF therapy.³ The study also includes an analysis of outcomes in patients who initially received aflibercept in the parent trials, potentially informing the effects of delayed initiation of AXPAXLI.

Results from SOL-1, a phase 3 study, have been described by the sponsor as demonstrating extended durability and disease control; however, peer-reviewed data remain limited, and independent validation is pending. Without published efficacy and safety outcomes, interpretation of the magnitude and clinical relevance of these findings remains constrained.

Clinical context

Wet AMD is a leading cause of irreversible vision loss in older adults, characterized by choroidal neovascularization driven by VEGF signaling.⁴ Intravitreal anti-VEGF agents—including ranibizumab, aflibercept, and faricimab—have transformed management but require frequent administration, often every 4 to 8 weeks in clinical practice.¹

Real-world studies suggest that treatment burden contributes to reduced adherence, with patients receiving fewer injections than in clinical trials, leading to inferior visual outcomes.² Moreover, long-term complications such as geographic atrophy and subretinal fibrosis remain areas of unmet need, even with effective VEGF suppression.³

Therapies designed to extend dosing intervals or provide sustained drug delivery have therefore become a major focus of retinal research. Approaches include port delivery systems, gene therapy, and biodegradable implants.

Drug background

AXPAXLI is an investigational, bioresorbable hydrogel implant delivering axitinib, a multi-target tyrosine kinase inhibitor that inhibits VEGF receptors and other angiogenic pathways. Axitinib is approved systemically for renal cell carcinoma but is being repurposed here for localized intraocular delivery.⁵

The hydrogel platform is designed to provide sustained drug release over several months, potentially enabling dosing intervals of 6 months or longer. This approach differs mechanistically from monoclonal antibody–based anti-VEGF therapies by targeting intracellular signaling pathways downstream of VEGF receptor activation.

Earlier-phase studies of OTX-TKI have suggested prolonged suppression of disease activity with reduced injection frequency, although these findings are based on relatively small cohorts.⁶ Robust phase 3 data are still emerging.

Interpretation and expert perspective

The initiation of a long-term extension study is consistent with regulatory and clinical expectations for chronic ophthalmic therapies, particularly those intended to modify disease trajectory or reduce treatment burden. Demonstrating sustained efficacy and safety over multiple years will be critical, especially given concerns about cumulative adverse effects such as intraocular inflammation or retinal toxicity.

The inclusion of endpoints related to fibrosis and macular atrophy reflects a growing recognition that anatomic control alone may not fully capture long-term visual outcomes. Whether continuous VEGF suppression can mitigate these processes remains an open question, with mixed evidence from existing anti-VEGF regimens.³

Importantly, the open-label design and lack of a comparator arm in SOL-X will limit causal inference. Outcomes will need to be interpreted in the context of prior randomized data from SOL-1 and SOL-R, as well as real-world benchmarks.

Limitations and next steps

Key limitations include the absence of published phase 3 results at the time of this report, limiting independent assessment of AXPAXLI’s efficacy and safety profile. Additionally, open-label extension studies are subject to selection bias, as participants who tolerate and respond to therapy are more likely to enroll.

Future steps will include peer-reviewed publication of SOL-1 and SOL-R results, as well as regulatory discussions if efficacy and safety outcomes support approval. Long-term data from SOL-X may also inform optimal timing of therapy initiation and its role relative to existing anti-VEGF agents.

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://doi.org/10.1056/NEJMoa062655

2. Ciulla TA, Pollack JS, Williams DF. Visual acuity outcomes and anti–vascular endothelial growth factor therapy intensity in neovascular age-related macular degeneration patients: a real-world analysis. Ophthalmol Retina. 2020;4(1):19-30. https://doi.org/10.1016/j.oret.2019.08.013

3. Jaffe GJ, Ying GS, Toth CA, et al. Macular atrophy in neovascular age-related macular degeneration. Ophthalmology. 2016;123(9):1936-1945. https://doi.org/10.1016/j.ophtha.2016.05.028

4. Lim LS, Mitchell P, Seddon JM, Holz FG, Wong TY. Age-related macular degeneration. Lancet. 2012;379(9827):1728-1738. https://doi.org/10.1016/S0140-6736(12)60282-7

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

6. Dugel PU, Singh RP, Koh A, et al. Phase 1 study of OTX-TKI (axitinib implant) in neovascular age-related macular degeneration. Ophthalmol Retina. 2021;5(8):769-778. https://doi.org/10.1016/j.oret.2020.11.015

7. ClinicalTrials.gov. A study to evaluate the long-term safety and efficacy of OTX-TKI in subjects with wet AMD (SOL-X). https://clinicaltrials.gov/study/NCT07516132