Summary: dosing and administration of vorolanib intravitreal insert compared with approved therapies

In the phase 3 program, vorolanib intravitreal insert 2.7 mg is given by in-office intravitreal injection every 6 months after aflibercept loading, and it requires no cold storage. Approved labeling for aflibercept 2 mg recommends monthly injections for 3 months followed by injections every 8 weeks. Aflibercept 8 mg is given monthly for 3 doses followed by every 8 to 16 weeks, with extension to every 20 weeks considered after 1 year of successful response. Faricimab is given monthly for 4 doses followed by one of three regimens with intervals of up to 16 weeks. Ranibizumab 0.5 mg is given monthly, with less frequent regimens described as not as effective. The ranibizumab port delivery system is refilled every 24 weeks but requires surgical implantation in an operating room and carries a boxed warning for endophthalmitis. The sustained-release TKI axitinib intravitreal hydrogel (AXPAXLI) is investigational; its sponsor plans an NDA submission in the fourth quarter of 2026. No head-to-head trials of vorolanib intravitreal insert against aflibercept 8 mg, faricimab, ranibizumab, the port delivery system, or axitinib intravitreal hydrogel were identified; the phase 3 comparator was aflibercept 2 mg every 8 weeks.

Sponsor description of approved wet AMD therapies

“There are multiple short acting effective and safe treatments for wet AMD available on the market, including large molecule anti-VEGF IVT drugs marketed under the brands names Lucentis, Eylea, Eylea HD, Vabysmo, Beovu, and Avastin (off label).” (opens the source at this quote in a new tab)
“These treatments are injected in a physician’s office either monthly, bi-monthly or in some patients every three to four months, which can cause inconvenience and often leads to reduced compliance and poor outcomes.” (opens the source at this quote in a new tab)
“The branded drug, SUSVIMO™, a port delivery technology for ranibizumab, was approved by the FDA in 2021 for the treatment of wet AMD and requires an initial surgical placement of the port.” (opens the source at this quote in a new tab)

Aflibercept 2 mg: labeled dosing in wet AMD

“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: labeled dosing in wet AMD

“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)

Faricimab: labeled dosing in wet AMD

“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)

Ranibizumab 0.5 mg: labeled dosing in wet AMD

“LUCENTIS 0.5 mg (0.05 mL of 10 mg/mL solution) is recommended to be administered by intravitreal injection once a month (approximately 28 days).” (opens the source at this quote in a new tab)
“Although not as effective, patients may also be treated with one dose every 3 months after 4 monthly doses.” (opens the source at this quote in a new tab)

Ranibizumab port delivery system: labeled dosing, surgical requirement, and boxed warning

“The recommended dose of SUSVIMO (ranibizumab injection) is 2 mg (0.02 mL of 100 mg/mL solution) continuously delivered via the SUSVIMO ocular implant with refills administered every 24 weeks (approximately 6 months).” (opens the source at this quote in a new tab)
“The SUSVIMO ocular implant must be surgically implanted in the eye or removed from the eye (if medically necessary) in an operating room using aseptic technique.” (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)

Axitinib intravitreal hydrogel (AXPAXLI): formulation and development status

“Ocular Therapeutix, Inc. (Ocular Therapeutix) is developing AXPAXLI which utilizes axitinib, a TKI, formulated in a hydrogel and delivered through an intravitreal injection.” (opens the source at this quote in a new tab)

“New Drug Application (NDA) submission for AXPAXLI in wet AMD planned for Q4 2026, with FDA alignment confirmed in May 2026 Type C meeting minutes.” (opens the source at this quote in a new tab)
“Following these changes, topline SOL-R results are now expected in the first quarter of 2028.” (opens the source at this quote in a new tab)

Axitinib intravitreal hydrogel (AXPAXLI): SOL-1 and SOL-R designs and SOL-1 results

“The superiority primary endpoint was met with 74.1% of subjects in the AXPAXLI (0.45 mg) arm maintaining vision at Week 36, a 17.5% risk difference (p=0.0006), compared to the aflibercept (2 mg) arm.” (opens the source at this quote in a new tab)
“Subjects in the first arm receive a single dose of AXPAXLI (0.45 mg) at Day 1 and are re-dosed at Weeks 24, 48, and 72.” (opens the source at this quote in a new tab)
“Subjects in the third arm receive a single dose of aflibercept (8 mg) at Day 1 and are re-dosed at Weeks 24, 48, and 72, aligned with the AXPAXLI treatment arm for adequate masking.” (opens the source at this quote in a new tab)

Novel retinal delivery therapies: published comparison table

Product	Mechanism of action	Duration of action	Phase of development
Vorolanib insert (EYP-1901)	“TKI: inhibition of all isoforms of VEGFR and PDGFR”	“Six months or longer”	“Phase 3”
Axitinib hydrogel insert (OTX-TKI)	“TKI: VEGFR-1, VEGFR-2, VEGFR-3 inhibition”	“Six months or longer”	“Phase 3”
Ranibizumab port delivery system	“VEGF-A inhibition”	“Up to 24 weeks”	“FDA approved”
Tarcocimab tedromer (KSI-301)	“VEGF-A, VEGF-B, PIGF inhibition”	“Up to six months”	“Phase 3”

Sponsor-described differentiation from other sustained-delivery products

“Only sustained-delivery TKI with Phase 3 repeat-dose safety” (opens the source at this quote in a new tab)

Head-to-head comparisons with aflibercept 8 mg, faricimab, ranibizumab, the port delivery system, or axitinib intravitreal hydrogel

No evidence found.

Axitinib intravitreal hydrogel (OTX-TKI): phase 1b rescue-free proportion and visual acuity at week 52

“By week 48, 67% of AXPAXLI-treated patients remained rescue-free, but this declined to 33% by week 52, suggesting a waning therapeutic effect near the end of the implant’s duration of action.” (opens the source at this quote in a new tab)
“There was an 89% reduction in anti-VEGF treatment burden at week 52 in the OTX-TKI arm.” (opens the source at this quote in a new tab)
“Mean change in BCVA at week 52 was –1.0 (6.0) letters in the OTX-TKI group and +2 (7.2) letters in the aflibercept group.” (opens the source at this quote in a new tab)

Sunitinib microparticle depot (GB-102): dose discontinued for anterior chamber migration and program discontinued

“After an interim safety analysis, the 2-mg GB-102 dose was discontinued after the initial dose because of a higher incidence of AEs. These AEs included anterior chamber microparticle migration and associated visual impairment and IOP elevation.” (opens the source at this quote in a new tab)
“The primary end point, median time to first supportive therapy, was 5 months in the 1-mg group. Moreover, 62% and 48% of patients did not require supportive therapy for at least 4 and 6 months, respectively.” (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)

Independent review: relative position of sustained-delivery platforms and uncertainty about pan-VEGF inhibition

“Intravitreal agents such as OTX-TKI and EYP-1901 have demonstrated encouraging durability and safety profiles in early-phase trials.” (opens the source at this quote in a new tab)
“Approaches like suprachoroidal CLS-AX may offer targeted posterior segment drug delivery with reduced anterior segment and systemic exposure.” (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.” (opens the source at this quote in a new tab)
“However, the clinical value of pan-VEGF inhibition remains uncertain.” (opens the source at this quote in a new tab)

Faricimab phase 3 trials: durability not compared with extended-interval aflibercept

“one limitation of the TENAYA and LUCERNE trials is the lack of direct comparison of durability of faricimab relative to the standard of care because the comparator in these studies was administered according to a fixed 8-week dosing regimen” (opens the source at this quote in a new tab)
“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)

Aflibercept 8 mg: injections through week 48 and limits of direct comparison with aflibercept 2 mg

“Patients who completed the week 48 visit received a mean of 6·1 injections in the aflibercept 8q12 group, 5·2 injections in the 8q16 group, and 6·9 injections in the 2q8 group.” (opens the source at this quote in a new tab)
“The limitations of this study included the inability for direct comparison at several timepoints between the aflibercept 8 mg and 2 mg groups after week 16 due to the different dosing regimens.” (opens the source at this quote in a new tab)

Duravyu (vorolanib intravitreal insert)

Product comparison