AXPAXLI (axitinib intravitreal implant)

As of September 2026, the axitinib intravitreal implant (AXPAXLI, OTX-TKI) is investigational and not approved in any country; if approved, it would be the first tyrosine kinase inhibitor commercialized for nAMD. The evidence establishes that, in the SOL-1 phase 3 trial of 342 treated participants, a single 450 µg implant was superior to a single aflibercept 2 mg injection in maintaining vision (loss of fewer than 15 letters) at Week 36 (74.1% versus 55.8%) and at Week 52 (65.9% versus 44.2%), with higher rescue-free rates at Week 52 (68.8% versus 47.7%). Through Week 52, safety data from 170 implant-treated participants showed more ocular adverse events in the study eye (52.9% versus 33.7%), more vitreous floaters (12.4% versus 1.2%), and intraocular inflammation in 7 participants, with no endophthalmitis, retinal vasculitis, retinal detachment, or implant migration to the anterior chamber in the implant arm.

Several questions are not answered by the current evidence. SOL-1 compared one dose of each agent rather than the implant with labeled aflibercept 2 mg maintenance dosing, and its key secondary endpoints of BCVA change from baseline were not reported as met. The estimated 72% reduction in injection burden is a post hoc projection against a modeled on-label regimen. Non-inferiority to aflibercept 2 mg every 8 weeks with repeat dosing every 24 weeks will be tested in SOL-R, with topline results expected in the first quarter of 2028, and no trial has compared the implant with aflibercept 8 mg, faricimab, or the port delivery system. SOL-1 enrolled treatment-naive participants selected for response to aflibercept loading, with mean baseline BCVA of 80.8 and 79.2 letters compared with 52 to 62 letters in other registration trials and 97.7% and 98.8% White participants, so applicability to previously treated eyes, eyes with poorer vision, and more diverse populations is uncertain; only the 21-participant U.S. phase 1 trial, using a different formulation, enrolled previously treated participants. Efficacy and safety after redosing, intraocular pressure outcomes, patient-reported outcomes, and long-term effects on fibrosis and macular atrophy have not been reported; SOL-X, an open-label extension with an estimated 850 participants, has an estimated primary completion date of 2030-08-01. No results have been published in peer-reviewed journals or posted to ClinicalTrials.gov, and company sources differ on analysis labels, p-values, SOL-R enrollment (631 versus 640 participants), the SOL-R primary endpoint timepoint, and SOL-R topline timing.

The regulatory timeline is as follows. The FDA issued a Special Protocol Assessment agreement letter for the SOL-1 trial design on October 30, 2023, with modification agreement letters on January 22, 2024 and February 24, 2025. SOL-1 randomization was completed in December 2024, and the Week 52 database lock occurred on February 5, 2026. After a May 2026 Type C meeting, the planned NDA is expected to include SOL-1 Week 52 efficacy and safety data, interim Week 52 safety data for a subset of SOL-R participants, and confirmatory evidence, to reach safety information for a minimum of 300 participants with at least one year of treatment; SOL-R efficacy data are not part of the submission. Following a September 2026 pre-NDA meeting, the company plans to submit the NDA in the fourth quarter of 2026 under the 505(b)(2) pathway, which it states may shorten FDA review by up to 60 days, to submit SOL-1 Year 2 safety data at the 120-day safety update to support repeat dosing, and describes a potential launch in 2027 if approved. No FDA expedited program designation, European Medicines Agency submission, or other ex-U.S. regulatory filing was identified.

Key evidence gaps for P&T committee review are the absence of a price, cost-effectiveness analysis, or budget impact model; the absence of peer-reviewed full results and independently verified analyses; the absence of repeat-dosing efficacy data and of safety data beyond Week 52; the lack of comparison with labeled or extended-interval anti-VEGF regimens and with other sustained-delivery options; limited data in previously treated participants; and the absence of patient-reported outcome data. Health technology assessments of other longer-interval anti-VEGF agents have linked acceptable pricing to the lowest-cost comparator, and U.S. economic models show that value depends on the injection frequency achieved in practice, which is lower than in registration trials.