Summary

No head-to-head trial has compared the axitinib intravitreal implant with aflibercept 8 mg, faricimab, the ranibizumab port delivery system, vorolanib intravitreal insert (DURAVYU, EYP-1901), or gene therapies. The only randomized comparisons are with aflibercept 2 mg: a single implant versus a single aflibercept 2 mg injection in SOL-1 (superiority), and implant every 24 weeks versus aflibercept 2 mg every 8 weeks in SOL-R (non-inferiority, results expected in the first quarter of 2028); SOL-R also includes an aflibercept 8 mg every 24 weeks arm with a planned Week 96 superiority comparison. Approved extended-durability comparators reached approval through non-inferiority trials against aflibercept 2 mg every 8 weeks (aflibercept 8 mg in PULSAR, 1009 treated participants; faricimab in TENAYA and LUCERNE, 1329 randomized participants) or monthly ranibizumab (port delivery system in Archway, 418 participants). Labeled maintenance intervals are every 8 weeks for aflibercept 2 mg, every 8 to 16 weeks for aflibercept 8 mg (every 20 weeks may be considered after one year), up to every 16 weeks for faricimab after 4 monthly doses, and refills every 24 weeks for the port delivery system, which carries a boxed warning for endophthalmitis and requires prior response to at least two anti-VEGF injections. SOL-1 enrolled participants selected for response to two aflibercept loading doses, with mean baseline BCVA of 80.8 and 79.2 letters, whereas the comparators' pivotal trials enrolled participants with lower baseline vision; cross-trial comparisons of durability or treatment burden are therefore limited, and the sponsor's own cross-trial treatment burden table is labeled as illustrative. Among other sustained-delivery tyrosine kinase inhibitors, the phase 3 LUGANO trial of vorolanib intravitreal insert did not meet its non-inferiority primary endpoint in the full dataset (August 2026). Gene therapies surabgene lomparvovec (ABBV-RGX-314) and 4D-150 are in phase 3, with topline data expected in the fourth quarter of 2026 and in 2027, respectively. Preclinical kinase-profiling studies sponsored by the developers of axitinib and vorolanib products reached different conclusions about axitinib inhibition of TIE2.

Competitive landscape described by the sponsor

“Anti-VEGF products that are currently approved by the FDA for the treatment of wet AMD include Vabysmo (faricimab), Eylea HD (aflibercept 8 mg), Lucentis (ranibizumab), Eylea (aflibercept 2 mg), Beovu (brolicizumab), and Susvimo (ranibizumab Port Delivery System).” (opens the source at this quote in a new tab)
“In addition, there are several companies pursuing gene therapies to treat wet AMD including, 4D Molecular Therapeutics, Adverum Biotechnologies, which was acquired by Eli Lilly and Company in 2025, and RegenxBio.” (opens the source at this quote in a new tab)

Aflibercept 2 mg (EYLEA): labeled nAMD dosing

“The recommended dose for EYLEA is 2 mg (0.05 mL of 40 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 days, monthly) for the first 3 months, followed by 2 mg (0.05 mL of 40 mg/mL solution) via intravitreal injection once every 8 weeks (2 months).” (opens the source at this quote in a new tab)
“Although not as effective as the recommended every 8 week dosing regimen, patients may also be treated with one dose every 12 weeks after one year of effective therapy.” (opens the source at this quote in a new tab)

Aflibercept 8 mg (EYLEA HD): labeled nAMD dosing

“The recommended dose for EYLEA HD is 8 mg (0.07 mL of 114.3 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 days +/- 7 days) for the first three doses, followed by 8 mg (0.07 mL of 114.3 mg/mL solution) via intravitreal injection once every 8 to 16 weeks, +/- 1 week.” (opens the source at this quote in a new tab)
“Extended dosing intervals (8 mg once every 20 weeks, +/- 1 week) may be considered after one year of successful response based on visual and anatomic outcomes.” (opens the source at this quote in a new tab)

Aflibercept 8 mg: PULSAR phase 3 results at Week 48

“Aflibercept 8q12 and 8q16 showed non-inferior BCVA gains versus aflibercept 2q8 (mean BCVA change from baseline +6·7 [SD 12·6] and +6·2 [11·7] vs +7·6 [12·2] letters).” (opens the source at this quote in a new tab)

Faricimab (VABYSMO): labeled nAMD dosing

“The recommended dose for VABYSMO is 6 mg (0.05 mL of 120 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 ± 7 days, monthly) for the first 4 doses, followed by optical coherence tomography and visual acuity evaluations 8 and 12 weeks later to inform whether to give a 6 mg dose via intravitreal injection on one of the following three regimens: 1) Weeks 28 and 44; 2) Weeks 24, 36 and 48; or 3) Weeks 20, 28, 36 and 44.” (opens the source at this quote in a new tab)

Faricimab: TENAYA and LUCERNE phase 3 results

“BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [-1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [-1·7 to 1·8]).” (opens the source at this quote in a new tab)

Ranibizumab port delivery system (SUSVIMO): indication, dosing, and boxed warning

“Neovascular (wet) Age-related Macular Degeneration (AMD) who have previously responded to at least two intravitreal injections of a VEGF inhibitor (1.1).” (opens the source at this quote in a new tab)
“The recommended dose of SUSVIMO (ranibizumab injection) is 2 mg (0.02 mL of 100 mg/mL solution) continuously delivered via the SUSVIMO implant with refills every 24 weeks (approximately 6 months). (2.2)” (opens the source at this quote in a new tab)
“The SUSVIMO implant has been associated with an up to 3-fold higher rate of endophthalmitis than monthly intravitreal injections of ranibizumab.” (opens the source at this quote in a new tab)

Ranibizumab port delivery system: Archway phase 3 results

“Adjusted mean change in BCVA score from baseline averaged over weeks 36 and 40 was +0.2 letters (standard error [SE], 0.5 letters) in the PDS Q24W arm and +0.5 letters (SE, 0.6 letters) in the monthly ranibizumab arm (difference, -0.3 letters; 95% confidence interval, -1.7 to 1.1 letters).” (opens the source at this quote in a new tab)
“Prespecified ocular adverse events of special interest were reported in 47 patients (19.0%) in the PDS Q24W arm and 10 patients (6.0%) in the monthly ranibizumab arm, which included, in the former arm, 4 (1.6%) endophthalmitis cases, 2 (0.8%) retinal detachments, 13 (5.2%) vitreous hemorrhages, 6 (2.4%) conjunctival erosions, and 5 (2.0%) conjunctival retractions.” (opens the source at this quote in a new tab)

Vorolanib intravitreal insert (DURAVYU, EYP-1901): LUGANO phase 3 topline results

“Despite the outperformance in key secondary endpoints, the primary endpoint of change from baseline in best corrected visual acuity (BCVA) versus 2 mg aflibercept on-label control was not achieved in the full dataset, confounded by this asymmetric cohort.” (opens the source at this quote in a new tab)
“54% of DURAVYU patients were supplement-free up to Week 56” (opens the source at this quote in a new tab)
“The Company anticipates potentially filing an NDA for DURAVYU for the potential treatment of wet AMD in the first half of 2027.” (opens the source at this quote in a new tab)

Suprachoroidal axitinib (CLS-AX): phase 1/2a OASIS trial

“Up to 1.0 mg CLS-AX, a highly potent TKI targeted to the suprachoroidal space (SCS) via the SCS Microinjector, was well tolerated, with stable mean visual acuity and mean CST.” (opens the source at this quote in a new tab)

Axitinib-based products in development

“Several axitinib-based therapies are in development for wet AMD and other retinal diseases, including Axpaxli (also known as Ocular Therapeutix-TKI, Ocular Therapeutix), CLS-AX (Clearside Biomedical), AR-14034 (Alcon), and GLK-401 (Glaukos).” (opens the source at this quote in a new tab)

Gene therapy: surabgene lomparvovec (ABBV-RGX-314) pivotal trial timing

“REGENXBIO expects to announce topline data with AbbVie from the ATMOSPHERE® and ASCENT® pivotal trials of sura-vec using subretinal delivery in Q4 2026.” (opens the source at this quote in a new tab)

Gene therapy: 4D-150 pivotal trial timing

“Completed enrollment for 4D-150 4FRONT-2 wet AMD Phase 3; topline data expected in H2 2027” (opens the source at this quote in a new tab)

Sponsor cross-trial treatment burden comparison at approximately 1 year

Product and trial	Reduction versus aflibercept 2 mg, loading doses included	Reduction versus aflibercept 2 mg, loading doses not included
Faricimab, TENAYA/LUCERNE phase 3	“14% (6.4 vs 7.4)”	“46% (2.4 vs 4.4)”
Aflibercept 8 mg, PULSAR phase 3	“29% (5.49 vs 7.7)”	“47% (2.49 vs 4.7)”
4D-150, PRISM phase 2b	“50% (3.97 vs 8)”	“51% (2.97 vs 6)”
Axitinib intravitreal implant, SOL-1 with SOL-R rescue criteria	“56% (3.95 vs 9)”	“72% (1.95 vs 7)”

“Results intended to be illustrative as the analysis is subject to the limitations of cross-trial comparisons, including different enrollment and rescue criteria.” (opens the source at this quote in a new tab)

Baseline vision in SOL-1 compared with other nAMD phase 3 trials

“SOL-1 Evaluates a Distinct nAMD Cohort with Excellent Baseline Vision” (opens the source at this quote in a new tab)
“mean BCVA: 52 to 62 letters” (opens the source at this quote in a new tab)

Hydrogel compared with other polymer implant platforms

“Hydrogel PLA/PLGA PVA” (opens the source at this quote in a new tab)
“Redosing interval 6-12 months1 N/A 6 months3” (opens the source at this quote in a new tab)
“Vehicle persistence 8-9 months1 Months to years2 18 to 24 months4” (opens the source at this quote in a new tab)

Durability and treatment burden across sustained-delivery TKIs: independent reviews

“Out of all the drugs explored in this section, thus far, EYP 1901, OTX-TKI and CLS-AX have shown good safety but moderate durability signals on PhI/IIa studies on nAMD patients who are sub-optimal responders to standard of care.” (opens the source at this quote in a new tab)

“Tyrosine kinase inhibitors delivered via intravitreal or suprachoroidal implants (e.g. EYP-1901, OTX-TKI, and CLS-AX) show potential for twice-yearly or less frequent dosing.” (opens the source at this quote in a new tab)

Proportion of PULSAR participants maintaining extended aflibercept 8 mg intervals to week 48

“A total of 251 (79%) of 316 patients in the aflibercept 8q12 group and 239 (77%) of 312 patients in the aflibercept 8q16 group maintained their assigned dosing regimen up to week 48. Overall, 523 (83%) of 628 patients who received aflibercept 8 mg maintained at least 12-week dosing intervals up to week 48.” (opens the source at this quote in a new tab)
“The minimum interval for all patients was 8 weeks, and dosing intervals could not be extended within the first year of treatment.” (opens the source at this quote in a new tab)

Baseline vision and eligibility differences that limit cross-trial comparison with PULSAR

“the mean baseline BCVA ETDRS letter score was 59·6 (SD 13·3), approximately Snellen equivalent 20/63” (opens the source at this quote in a new tab)
“Furthermore, the PULSAR study enrolled patients with a larger total lesion size of up to 12 disc areas and required foveal involvement, whereas patient eligibility in TENAYA and LUCERNE was restricted to those with lesion sizes of up to 9 disc areas without foveal involvement.” (opens the source at this quote in a new tab)
“Differences between trials in the criteria used to implement regimen modifications, the timepoints at which dose-modification criteria were assessed, and in study populations, limit cross-trial comparisons.” (opens the source at this quote in a new tab)

Faricimab dosing-interval distribution at week 48 in TENAYA and LUCERNE

“At week 48, approximately 80% of faricimab-treated patients in both TENAYA and LUCERNE were on 12-week or 16-week dosing intervals, with 107 (34·0%) patients in TENAYA and 104 (32·9%) patients in LUCERNE on extended dosing regimens of every 12 weeks, and 144 (45·7%) patients in TENAYA and 142 (44·9%) patients in LUCERNE on 16-week dosing” (opens the source at this quote in a new tab)

Comparator choice and masking-related limits on durability comparison in the faricimab trials

“The registrational phase 3 trials of faricimab for nAMD were not designed for head-to-head comparison of faricimab’s durability versus aflibercept because extended fixed 12-week or fixed 16-week dosing regimens have not been studied in double-masked phase 3 registrational trials for aflibercept.” (opens the source at this quote in a new tab)
“Fixed 8-week aflibercept dosing, which was used in the pivotal phase 3 trials of aflibercept, was therefore the most appropriate regimen against which to evaluate noninferiority of a new treatment, especially considering the potential for extended dosing with faricimab at up to 16-week repeating intervals.” (opens the source at this quote in a new tab)
“Finally, the assessment of the potential for faricimab to reduce treatment burden and improve quality of life might also be limited by the fact that at the time of the primary analysis, all patients returned for monthly visits to maintain masking.” (opens the source at this quote in a new tab)

Injections and treatment completion over 2 years in TENAYA and LUCERNE

“Of 1326 patients treated across TENAYA/LUCERNE, 1113 (83.9%) completed treatment” (opens the source at this quote in a new tab)
“Moving to the T&E regimen during year 2 resulted in significantly fewer injections of faricimab compared with aflibercept Q8W dosing (median, 10 injections vs. 15 injections from baseline through year 2; 3 injections vs. 6 injections during the year 2 T&E phase); however, per the design of the study, aflibercept was given at fixed intervals throughout the 2-year study period.” (opens the source at this quote in a new tab)

Sustained-delivery tyrosine kinase inhibitor platforms compared: independent review

“EYP-1901 is a sustained-delivery implant that combines Durasert E with a multikinase pan-VEGF inhibitor vorolanib. The implant is designed to release vorolanib at near zero order kinetics for 9 months and to be completely bioerodible.” (opens the source at this quote in a new tab)
“Among these emerging therapies, platforms combining intravitreal sustained-release technology with pan-VEGF inhibition (eg, EYP-1901, OTX-TKI, CLS-AX) currently appear the most balanced in terms of efficacy, safety, and durability. However, the clinical value of pan-VEGF inhibition remains uncertain.” (opens the source at this quote in a new tab)
“Despite evidence suggestive of the beneficial biologic effect of X-82, the phase 2 trial was terminated early because of concerns regarding elevated liver enzyme elevations and high study discontinuation rate because of AEs.” (opens the source at this quote in a new tab)
“At this time, the sponsor has discontinued further investigation of GB-102.” (opens the source at this quote in a new tab)

Endophthalmitis risk attributed to the implantation procedure and to indwelling devices

“Review of the case details including surgical videos identified 8 cases where the surgical procedures may have contributed to the risk of developing endophthalmitis.” (opens the source at this quote in a new tab)
“A large scleral incision (>3.5 mm) resulting in an inadequate seal around the implant, may increase the risk of endophthalmitis occurring soon after the PDS surgery.” (opens the source at this quote in a new tab)
“Notably, these rates are similar to what has been observed for FA implants versus systemic therapy (1.3% vs. 0%, respectively) over 24 months in patients with noninfectious uveitis.” (opens the source at this quote in a new tab)

Vision course after implantation in Archway

“Patients treated with the PDS Q24W experienced a transient and reversible postsurgical drop of approximately 1 ETDRS line in vision after implant insertion, with vision returning to baseline by week 8.” (opens the source at this quote in a new tab)
“A similar proportion of patients in the PDS Q24W arm (80.5%) and the monthly ranibizumab arm (82.2%) showed a BCVA of 69 letters or better at the average of weeks 36 and 40 (Table S5, available at www.aaojournal.org).” (opens the source at this quote in a new tab)

AXPAXLI (axitinib intravitreal implant)

Product comparison