VEGF Inhibitor Implant Preserves Visual Acuity, Retinal Anatomy in Wet AMD

DENVER — A sustained-release VEGF inhibitor implant outperformed standard anti-VEGF therapy for maintaining visual acuity in neovascular, or wet, age-related macular degeneration (AMD), showed a randomized trial reported here.

Among patients with good baseline visual acuity, 74.1% maintained that status at 36 weeks with the axitinib implant OTX-TKI as compared with 55.8% taking standard-dose aflibercept (Eylea). The advantage in favor of the implant persisted out to 52 weeks (65.9% vs 44.2%). Three-fourths of patients randomized to OTX-TKI required no rescue anti-VEGF therapy at 36 weeks versus 56.4% of patients randomized to aflibercept. A similar proportion of patients in both groups maintained improvements in best-corrected visual acuity (BCVA) and central subfield thickness (CST) at 36 weeks.

The results showed that upfront improvements in visual and anatomical measurements are maintained in a higher proportion of patients treated with the axitinib implant, said Patricio G. Schlottmann, MD, of the Charles Ophthalmic Center in Buenos Aires, at the Association for Research in Vision and Ophthalmology meeting.

“This is the first trial to demonstrate durability of more than 9 months,” he noted. “This is unmatched durability. Anatomic stability was achieved to sustain disease control, and the treatment was very well tolerated.”

Providing context for the results, Schlottmann explained that the study population had good baseline visual acuity — a mean BCVA of 70 letters — as compared with contemporary trials of anti-VEGF therapy for AMD. In this type of patient population, maintaining visual acuity has greater clinical significance as compared with patients who have worse baseline visual acuity.

“After two loading doses, they reached a visual acuity of 80,” he said. “Let me remind you that 85 is full 20/20 vision, so these patients had very little room to keep gaining vision.”

During a discussion that followed the presentation, an unidentified member of the audience asked about the 25% of patients who did not have durable maintenance of baseline visual acuity and whether specific characteristics were associated with lack of treatment effect.

“We recognized these patients early on as ones that will need to be rescued, regardless of the treatment they receive,” said Schlottmann. “We don’t have any biomarkers if that is what you are looking for. We have a massive amount of data, and we can look into that.”

OTX-TKI is a hydrogel delivery platform consisting of a bioresorbable polymer matrix combined with the VEGF tyrosine kinase inhibitor axitinib. The oral formulation of axitinib (Inlyta) has FDA-approved indications in renal cell carcinoma. The implant is designed to achieve sustained release of the drug to maintain intraocular levels with complete bioresorption. A phase I study of the intravitreal implant showed a 90% reduction in the frequency of injections for AMD, which provided the basis for the phase III randomized SOL-1 trial comparing OTX-TKI and aflibercept 2 mg in patients with AMD and preserved visual acuity.

Eligible patients had previously untreated choroidal neovascularity associated with AMD, a BCVA of at least 54 letters (~20/80 Snellen equivalent), and a CST of 500 µm or less. All patients received two doses of aflibercept 4 weeks apart and then were reassessed for randomization, which was limited to patients who had a BCVA improvement of ≥10 letters or a BCVA of ≥84 letters plus a CST ≤350 µm.

The primary endpoint was maintenance of visual acuity at 36 weeks, defined as a <15-letter loss from baseline. Follow-up continued to 52 weeks. Patients received rescue treatment if BCVA decreased by 15 letters or more or if they developed new macular hemorrhage. Data analysis included 344 randomized patients, 328 of whom completed 52 weeks of follow-up.

Schlottmann pointed out that the study population had “excellent” visual acuity from the outset, averaging about 70 letters at enrollment and about 80 letters at randomization. CST averaged 303 µm at screening and 219-227 µm at randomization.

Significantly more patients randomized to OTX-TKI met the primary endpoint, an absolute difference of almost 20% (P=0.0006). At 52 weeks, 66% of patients in the OTX-TKI arm had maintained BCVA compared with 44% of the aflibercept group (P<0.0001). Three-fourths of patients randomized to OTX-TKI had received no rescue treatment by 36 weeks as compared with 56% of the aflibercept group (P=0.0006).

Anatomical improvement was maintained in the OTX-TKI group, averaging 219 µm at randomization and 238 µm at 36 weeks. Corresponding numbers in the control arm were 227 and 258 µm.

About 11% to 12% of patients in each arm had at least one non-ocular serious adverse event (AE), and fewer than 1% of patients in both arms combined had ocular serious AEs involving the study eye.