Phase 3 data support OTX-TKI's durability in wet AMD: 1 injection, 1 year

A novel intravitreal axitinib hydrogel demonstrated durable disease control in patients with treatment-naive neovascular age-related macular degeneration (AMD), with superior maintenance of visual acuity and anatomic outcomes compared with aflibercept 2 mg through 1 year. In a recent Ophthalmology Times® Rapid Readout, Arshad M. Khanani, MD, MA, FASRS, managing partner, director of clinical research and director of fellowship at Sierra Eye Associates and clinical professor at the University of Nevada, Reno School of Medicine, provided an overview of the SOL-1 phase 3 pivotal trial of OTX-TKI (Axpaxli; Ocular Therapeutix). Khanani was an investigator in the clinical trial.

Trial design and special protocol assessment

SOL-1 (NCT06223958) was designed to evaluate the efficacy and safety of OTX-TKI in treatment-naive patients with neovascular AMD. Patients with 20/80 or better vision received 2 loading doses of aflibercept 2 mg before randomization, with eligibility requiring either 20/20 vision or a 10-letter gain. At randomization, patients were assigned to receive 1 injection of OTX-TKI or aflibercept 2 mg, then followed monthly. The primary end point was the proportion of subjects maintaining vision (loss of fewer than 15 Early Treatment Diabetic Retinopathy Study letters) at week 36.

Khanani noted that SOL-1 is the first superiority trial evaluating maintenance of vision following a single injection of OTX-TKI vs a single injection of aflibercept 2 mg to assess the durability of each therapy. The study was designed in accordance with the 2023 US Food and Drug Administration (FDA) guidance, which requires the comparator arm to follow the same dosing schedule as the investigational treatment, without sham injections. The FDA assigned a special protocol assessment (SPA) to the study. “With acceptance of the SPA, study design, end points, and analysis plan cannot be changed,” he said. “Conducting a trial under a SPA helps to de-risk the regulatory process and possibly get a faster approval.”

He flagged an important interpretive consideration: Because patients entered randomization at peak visual acuity following 2 aflibercept loading doses, “the data from this trial need to be looked at in a different way.” He also noted that SOL-1 is a trial designed for regulatory approval and that “this is not how we practice.”

Primary and secondary end points

The primary end point was met. At week 36, 74.1% of patients treated with OTX-TKI maintained vision vs 55.8% with aflibercept (P = .0006). At week 52, those figures were 65.9% and 44.2%, respectively. “About two-thirds of patients going 1 year in terms of maintenance of visual acuity” was how Khanani framed the week 52 result, noting that the head-to-head comparison gave both agents the same opportunity.

On anatomic end points, the proportion of patients with central subfield thickness (CST) of 350 μm or less was 68.8% vs 52.9% at week 36 and 64.7% vs 43.6% at week 52. The proportion with 30 μm or less increase in CST from baseline was 55.9% vs 37.8%. OTX-TKI also delivered superior intraretinal and subretinal fluid control through week 52.

On rescue treatment, 74.7% of patients treated with OTX-TKI were rescue free at week 36 vs 56.4% with aflibercept, and 68.8% vs 47.7% at week 52. OTX-TKI also significantly delayed time to first rescue injection, with the Kaplan-Meier curve showing that aflibercept patients reached that end point approximately 24 weeks earlier.

Safety findings

There were no treatment- or procedure-related serious adverse events, no endophthalmitis, and no retinal vasculitis. Every case of inflammation was evaluated with fluorescein angiography to rule out vasculitis. Intraocular inflammation was mild to moderate and resolved with topical treatment.

The notable adverse event was vitreous floaters, reported in 12.4% of patients treated with OTX-TKI vs 1.2% with aflibercept, corresponding to the period when the hydrogel begins to dissolve, around weeks 30 to 36. “There was no impact on visual acuity, and all cases were mild to moderate, and these are not cases associated with intraocular inflammation, and these are not cases that were associated with cataract formation,” Khanani said. He characterized the overall safety profile as similar to currently available agents, with the exception of hydrogel dissolution–related floaters.

Overall assessment

Summarizing the data set, Khanani described OTX-TKI as a “novel, first-in-class tyrosine kinase inhibitor in a sustained delivery platform with a durability of 9 to 12 months in patients with wet AMD.” He expressed hope that the drug would be approved and improve real-world outcomes by addressing the treatment burden associated with frequent injections.