Duravyu (vorolanib intravitreal insert)

Wet age-related macular degeneration

Also known as EYP-1901

Manufacturer: EyePoint
Regulatory submission: NDA planned for the first half of 2027
Launch: Not announced
Last updated: September 19, 2026

Section

Clinical evidence

APEX

33 evidence topics · 5 sources

Objective

Study purpose: oral vorolanib (X-82) with as-needed anti-VEGF injections

“The safety and efficacy of X-82, an orally administered inhibitor of vascular endothelial growth factor (VEGF) and platelet-derived growth factor, was investigated for treatment of wet age-related macular degeneration (AMD) in a phase II clinical trial.” (opens the source at this quote in a new tab)

Relationship of X-82 to EYP-1901

“An oral formulation of vorolanib was previously studied in the phase II APEX Trial in patients with wAMD, which suggested its efficacy in wAMD.” (opens the source at this quote in a new tab)

Location and study date

Sites and registry dates

“This study was conducted at 39 sites in the United States. There were 36 sites that screened subjects and 3 sites that did not screen any subjects.” (opens the source at this quote in a new tab)

Field	Quoted record
Study start (actual)	“2015-03-16”
Primary completion (actual)	“2017-12-12”

Study design

Randomized, placebo-controlled dose-finding design

“This phase II, randomised, double-masked, placebo-controlled trial enrolled subjects with a prior diagnosis of exudative AMD having received at least two intravitreal injections of anti-VEGF therapy.” (opens the source at this quote in a new tab)
“At each 4-week interval visit for 52 weeks, subjects were to be assessed to determine if rescue treatment was needed with anti-VEGF therapy.” (opens the source at this quote in a new tab)

Early termination

“Interim analysis found study had achieved primary objective” (opens the source at this quote in a new tab)

“Due to gastrointestinal and hepatobiliary adverse events and the fulfilment of the primary endpoint, the trial was stopped prematurely after a second interim analysis.” (opens the source at this quote in a new tab)

Interim analyses and the Data Safety Monitoring Committee recommendation to terminate

“Based on a planned, unbiased, interim analysis conducted, once 90% of all subjects had reached their week 36 visit, it was concluded that the study had already achieved its primary endpoint of demonstrating non-inferiority in visual acuity of those on X-82 when compared with placebo.” (opens the source at this quote in a new tab)
“However, due to the relatively frequent occurrence of liver enzyme elevations, about 20% of the patients treated with X-82, and the number of patients discontinuing therapy due to AEs, ranging from 20% to 36% in the X-82 treated patients, the Data Safety Monitoring Committee recommended to the sponsor to terminate the trial due to an insufficient benefit to risk profile.” (opens the source at this quote in a new tab)
“The sponsor agreed with the recommendations, and all patients were subsequently discontinued from the study. A total of 28 (37%) of enrolled subjects were discontinued due to study termination.” (opens the source at this quote in a new tab)

Masking, trial duration, and monthly assessments

“Participants, physicians and care providers were all blinded to treatment arms.” (opens the source at this quote in a new tab)
“The duration of the trial was planned for 56 weeks with 52 weeks of treatment followed by 1 month off treatment.” (opens the source at this quote in a new tab)
“At each monthly visit, ETDRS BCVA assessment, ophthalmic examination, SD-OCT imaging, laboratory assessment, urinalysis, vital signs and an ECG were completed.” (opens the source at this quote in a new tab)
“Eligible patients showing a response to intravitreal anti-VEGF therapy and fulfilling all other study criteria returned on Day 1 to be randomised to a study treatment group and to receive another intravitreal anti-VEGF treatment.” (opens the source at this quote in a new tab)

Eligibility criteria

Key inclusion criteria

“Must have demonstrated a reduction in macular fluid or macular thickness in the study eye 14 days following an anti-VEGF injection at Screening Visit 1” (opens the source at this quote in a new tab)

Prior treatment requirement and key exclusion criteria

“Prior to enrolment, subjects were required to have received injections at intervals of 8 weeks or less and to have consistent macular fluid that was responsive to anti-VEGF therapy.” (opens the source at this quote in a new tab)
“pars plana vitrectomy within 30 days, the presence of proliferative diabetic retinopathy, prior glaucoma surgery and/or any other underlying diseases potentially limiting best-corrected visual acuity (BCVA) were excluded” (opens the source at this quote in a new tab)
“a history of a cerebral vascular accident, transient ischemic attack, significant cardiac disease or evidence of active gastrointestinal disease were excluded.” (opens the source at this quote in a new tab)

Treatment

Treatment groups

“Subjects were randomised equally into four groups that received either daily 50mg, 100mg or 200mg dosages of X-82 or a placebo tablet.” (opens the source at this quote in a new tab)

Permitted as-needed anti-VEGF agents and duration of oral dosing

“Daily dosing was continued for 52 weeks followed by a 4-week observation period.” (opens the source at this quote in a new tab)
“Bevacizumab, ranibizumab and aflibercept were all allowed, based on investigator preference, but the drug had to remain unchanged from what the patient received prior to study enrolment and the drug remained the same for the duration of the trial.” (opens the source at this quote in a new tab)
“These agents remained unchanged to eliminate the potential for any unwanted effect in our study results that could be attributed to a switch in an anti-VEGF agent.” (opens the source at this quote in a new tab)

Criteria for as-needed anti-VEGF retreatment

“Patients received anti-VEGF therapy at the screening visit and returned within 14 days to document an adequate anatomic response to anti-VEGF therapy.” (opens the source at this quote in a new tab)
“As-needed treatment with anti-VEGF was permitted if there was any increase in macular fluid/thickness compared with SD-OCT at screening visit 2 or if there was new or increased macular hemorrhage secondary to nAMD.” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using visual acuity noninferiority to placebo as the primary endpoint

Registered primary outcome

“The primary outcome is the change in the visual acuity score from Day -1 to 52 weeks after randomization.” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Randomized and analyzed participants

“A total of 157 subjects were randomly assigned and treated in the study.” (opens the source at this quote in a new tab)

“Approximately 132 subjects will be randomized into one of the four arms (33 subjects per dose group).” (opens the source at this quote in a new tab)

Intention-to-treat and per-protocol participants with week 52 data

“Overall, the ITT population started with a mean visual acuity of 71.0 (n=157; Snellen 20/40) and ended with a mean of 72.3 (n=81; Snellen 20/40) at week 52.” (opens the source at this quote in a new tab)
“Overall, the PP population started with a mean ETDRS BCVA score of 71.7 letters (n=92; Snellen 20/40) and ended with a mean of 71.2 letters (n=68; Snellen 20/40) at week 52.” (opens the source at this quote in a new tab)

Description of analysis sets

Primary outcome population

“Analysis restricted to subjects who completed 52 weeks of treatment” (opens the source at this quote in a new tab)

Intention-to-treat and per-protocol analysis sets and major protocol deviations

“The ITT analysis included every patient that was randomised into the clinical trial. The PP population consisted of all ITT subjects without any major violation deviation of the protocol.” (opens the source at this quote in a new tab)
“The analyses of primary and secondary efficacy outcomes were performed on the PP population as a sensitivity analysis.” (opens the source at this quote in a new tab)
“Of those involved in ITT population analysis, 65% (102/157) were able to avoid major protocol deviations in dosing (defined as missing ≥15% of planned X-82 doses for the entire study)” (opens the source at this quote in a new tab)

Results

Participant disposition

Disposition by treatment group

Milestone	X-82 50 mg	X-82 100 mg	X-82 200 mg	Placebo
Started	“40”	“39”	“39”	“39”
Completed	“29”	“22”	“25”	“27”
Not completed	“11”	“17”	“14”	“12”

Reasons for premature discontinuation of study treatment

“Seventy-five (47.8%) subjects had study treatment prematurely discontinued for the following reasons: study termination (28 (37.3%) subjects), AE (27 (36.0%) subjects), withdrawal of consent (8 (10.7%) subjects), ‘other’ (5 (6.7%) subjects), SAEs (4 (5.3%) subjects), protocol deviation (1 (1.3%) subject), death (1 (1.3%) subject) and investigator decision (1 (1.3%) subject).” (opens the source at this quote in a new tab)

Baseline characteristics

Age and baseline visual acuity by treatment group

Characteristic	X-82 50 mg, 40 participants	X-82 100 mg, 39 participants	X-82 200 mg, 39 participants	Placebo, 39 participants
Age, mean, years	“75.7”	“73.5”	“75.0”	“75.9”
Best corrected visual acuity, mean, letters	“72.3”	“71.2”	“71.9”	“68.8”

Efficacy results

Primary endpoint and anti-VEGF injection counts

“The primary endpoint of non-inferiority of visual acuity compared with placebo was demonstrated in all groups receiving X-82 (p<0.001).” (opens the source at this quote in a new tab)
“There was a dose-dependent trend in the number of injections over a 52-week period, with the 50 mg (n=40), 100 mg (n=39), 200 mg (n=39) and placebo (n=39) group requiring 6.7, 6.0, 4.7 and 8.1 injections, respectively.” (opens the source at this quote in a new tab)

Registry primary outcome: completers at week 52

Group	Participants analyzed	Mean (SD) change in visual acuity, letters
X-82 50 mg	“23”	“0.2(4.14)”
X-82 100 mg	“19”	“-0.9(6.57)”
X-82 200 mg	“17”	“1.7(5.58)”
Placebo	“22”	“-0.3(10.63)”

Noninferiority estimates by dose and proportion losing fewer than 15 letters

“demonstrated a non-inferiority of visual acuity at the week 52 visit in all groups receiving X-82 when compared with placebo (−4.02 letters in the 50 mg group (p<0.000001), −1.71 letters in the 100 mg group (p<0.000001) and −2.33 letters in the 200 mg group (p<0.000001)).” (opens the source at this quote in a new tab)
“The negative estimates indicate less loss (or better maintenance) of visual acuity compared with placebo.” (opens the source at this quote in a new tab)
“Those in the 50 mg, 100 mg, 200 mg and placebo groups had a mean change from baseline in visual acuity of −0.4, −0.9, 0.3 and −0.5 letters at Week 52, respectively.” (opens the source at this quote in a new tab)
“Overall, 95.6% (87/91) of all patients lost fewer than 15 ETDRS letters by week 52.” (opens the source at this quote in a new tab)

Participants requiring no further anti-VEGF injection and median time to first injection

“Interestingly, there were several instances in which patients did not require another anti-VEGF injection after the final screening treatment was completed.” (opens the source at this quote in a new tab)
“This was more common in those receiving X-82 (7.5% (3/40), 10.3% (4/39) and 20.5% (8/39) in the 50 mg, 100 mg and 200 mg groups, respectively) than those receiving placebo (2.6% (1/39)) but was not statistically analysed and also does not take into account follow-up time.” (opens the source at this quote in a new tab)
“The median time to first anti-VEGF injection was 4.3 weeks for placebo-treated patients and 7.9, 8.1 and 8.4 weeks for patients administered 50 mg, 100 mg or 200 mg of X-82, respectively” (opens the source at this quote in a new tab)

Per-protocol anti-VEGF injection counts by dose

“In the per-protocol group, an average of 6.3 injections were required per year.” (opens the source at this quote in a new tab)
“Looking at the individual groups, there was a dose-dependent trend to less as-needed anti-VEGF injections in patients receiving X-82 compared with sham: 6.4 injections in the 50-mg group, 5.1 injections in the 100-mg group, 4.8 injections in the 200-mg group, and 8.1 injections in the sham group.” (opens the source at this quote in a new tab)

Subretinal fluid on optical coherence tomography at screening and week 52

“In the placebo group, 56.4% (22/39) of patients were noted to have subretinal fluid on SD-OCT during the screening visit 2, while 81.8% (18/22) had presence of subretinal fluid at 52 weeks.” (opens the source at this quote in a new tab)
“In contrast, at the screening visit 2, 60% (24/40) of the 50 mg group, 51.3% (20/39) of the 100 mg group and 56.4% (22/39) of the 200 mg group had subretinal fluid on SD-OCT, while 78.3% (18/23), 52.6% (10/19) and 41.2% (7/17) of the 50 mg, 100 mg and 200 mg groups, respectively, had subretinal fluid on imaging on the week 52 follow-up.” (opens the source at this quote in a new tab)

Fellow eye conversion to exudative AMD by 52 weeks

“In the placebo group, 12.5% (3/24) of subjects with unilateral disease at baseline developed exudative AMD in their fellow eyes by 52 weeks, compared with 3.8% (1/26), 0% (0/27) and 0% (0/23) in the 50 mg, 100 mg, and 200 mg X-82 groups, respectively.” (opens the source at this quote in a new tab)

Health-related quality of life and patient-reported outcomes

No evidence found.

Safety results

Authors' benefit-risk conclusion

“Given the limited tolerability and safety issues observed, X-82 does not have a sufficient benefit to risk profile in treatment of patients with AMD.” (opens the source at this quote in a new tab)

Selected adverse events with oral X-82

Event	X-82 50 mg	X-82 100 mg	X-82 200 mg	Placebo
Serious adverse events, total	“6/40 (15.00%)”	“7/39 (17.95%)”	“3/39 (7.69%)”	“2/39 (5.13%)”
Alanine aminotransferase increased	“8/40 (20.00%)”	“11/39 (28.21%)”	“9/39 (23.08%)”	“2/39 (5.13%)”
Diarrhoea	“1/40 (2.50%)”	“4/39 (10.26%)”	“9/39 (23.08%)”	“2/39 (5.13%)”
Dysgeusia	“3/40 (7.50%)”	“5/39 (12.82%)”	“10/39 (25.64%)”	“0/39 (0.00%)”
Hair color change	“2/40 (5.00%)”	“10/39 (25.64%)”	“13/39 (33.33%)”	“0/39 (0.00%)”

Discontinuation of oral vorolanib development in AMD

“The APEX Trial was stopped prematurely due to gastrointestinal and hepatobiliary AEs associated with oral vorolanib use such as elevated liver enzymes, and due to the fulfillment of the primary endpoint (noninferiority to placebo).” (opens the source at this quote in a new tab)
“EYP-1901 was developed as a localized, intravitreal, sustained-delivery formulation of vorolanib in an attempt to reduce the injection burden of wAMD treatment and also reduce systemic adverse effects of vorolanib.” (opens the source at this quote in a new tab)

Treatment-emergent adverse events, severity, discontinuations, and death

“Overall, 148 (94.3%) subjects experienced at least one treatment-emergent adverse event (TEAE) and 74 (47.1%) subjects experienced one treatment-related TEAE.” (opens the source at this quote in a new tab)
“A total of 16 (10.2%) subjects overall experienced at least one severe TEAE, with 4 (2.5%) of these subjects having a TEAE that was considered related to study treatment.” (opens the source at this quote in a new tab)
“In total, 39 (24.8%) subjects experienced at least one TEAE leading to permanent discontinuation of study treatment (8 (20.0%), 12 (30.8%), 15 (38.5%) and 4 (10.3%) subjects in the 50 mg, 100 mg, 200 mg and placebo groups, respectively).” (opens the source at this quote in a new tab)
“One (2.6%) subject died during the study (sudden cardiac death) during treatment with X-82 (100 mg), which was not considered related to study treatment.” (opens the source at this quote in a new tab)

Early termination for sustained hepatic abnormalities by dose

“In several instances, these elevations resolved without any intervention; however, 5.0% (2/40), 15.4% (6/39) and 17.9% (7/39) in the 50 mg, 100 mg and 200 mg groups, respectively, required early termination of the trial secondary to sustained hepatic abnormalities.” (opens the source at this quote in a new tab)
“No patients from the placebo group required early termination for liver enzyme elevations.” (opens the source at this quote in a new tab)

Study limitations

Summary

APEX evaluated daily oral vorolanib (X-82) at 50, 100, and 200 mg, not the intravitreal insert, so its efficacy results do not transfer directly to EYP-1901; its relevance to this report is the systemic adverse event profile of vorolanib at oral exposures. The trial randomized 157 participants and was stopped early after a second interim analysis, with 103 of 157 participants (65.6%) completing the study. The registry primary outcome analysis was restricted to participants who completed 52 weeks of treatment. The comparator was placebo plus as-needed anti-VEGF injections rather than a fixed-interval anti-VEGF regimen. Statements here are drawn from the full publication and the registry record.