Registered study objective

“This is a phase 2 randomized, double -masked study comparing the efficacy of EYP-1901 at 2 dose levels: 2060 microgram (mcg) and 3090 mcg against aflibercept.” (opens the source at this quote in a new tab)

Role of DAVIO 2 in the development program

“the DAVIO 2 clinical trial was designed to support the initiation of Phase 3 clinical trials based on feedback received from the U.S. Food and Drug Administration (FDA) at a Type C meeting last year.” (opens the source at this quote in a new tab)

Post hoc analysis objective: supplemental injection patterns

“OBJECTIVE: Understand patterns of supplemental injections in DAVIO 2” (opens the source at this quote in a new tab)

Sites and study period

“This Phase 2 prospective, randomized, double-masked study was conducted in previously treated subjects with wet age-related macular degeneration (wAMD) at 39 sites in the United States between 30 June 2022 and 24 April 2024.” (opens the source at this quote in a new tab)

Registry dates

Field	Quoted record
First submitted	“2022-05-09”
Results first posted	“2025-10-02”

Completion of enrollment

“The trial exceeded its original target of 144 patients, enrolling a total of 160 patients.” (opens the source at this quote in a new tab)

Registered design

Field	Quoted record
Allocation	“Randomized”
Interventional model	“Parallel Assignment”
Primary purpose	“Treatment”
Study periods	“This study consists of a screening period (up to 14 days) and treatment period (56 weeks).”

Masking and on-label comparator

“Design: Multi-center, randomized, double-masked trial in patients with previously treated wet AMD” (opens the source at this quote in a new tab)
“Aflibercept on-label control required by FDA” (opens the source at this quote in a new tab)

Prespecified supplemental aflibercept criteria

“BCVA reduction ≥5 letters from best on-study measurement due to wet AMD AND CST increase ≥75 µm from lowest on-study measurement” (opens the source at this quote in a new tab)
“BCVA reduction ≥10 letters from best on-study measurement due to wet AMD” (opens the source at this quote in a new tab)
“CST increase ≥100 µm from lowest on-study measurement from 2 consecutive visits” (opens the source at this quote in a new tab)
“Vision-threatening hemorrhage, new or worsening, due to wet AMD” (opens the source at this quote in a new tab)

Definition of supplemental therapy

“Supplemental therapy was any unscheduled injection of aflibercept, whether or not a subject had met rescue criteria.” (opens the source at this quote in a new tab)
“For either of the EYP-1901 arms, any aflibercept injection following the Week 8 visit was supplemental therapy.” (opens the source at this quote in a new tab)

Design changes between the 2022 plan and the conducted trial

“Diagnosed within past 9 months” (opens the source at this quote in a new tab)
“Central subfield thickness > 400 µm” (opens the source at this quote in a new tab)
“Retinal pigment epithelium detachment thickness > 300 µm” (opens the source at this quote in a new tab)

“Diagnosed with wAMD at any time” (opens the source at this quote in a new tab)
“Excluded CST >350 µm, IRF >25 µm, RPED >400 µm” (opens the source at this quote in a new tab)

Key inclusion criteria

“Documented diagnosis of wAMD in the study eye, with disease onset any time prior to the Screening Visit.” (opens the source at this quote in a new tab)
“Previously treated with at least 2 anti-VEGF intravitreal injections (that is, bevacizumab, ranibizumab, aflibercept or faricimab) for wAMD per standard of care in the study eye within 6 months prior to the Screening Visit.” (opens the source at this quote in a new tab)
“Best corrected visual acuity (BCVA) early Treatment Diabetic Retinopathy Study (ETDRS) letter score of 35 letters (20/200 Snellen equivalent) to 85 letters (20/20 Snellen equivalent) in the study eye at the Screening Visit and on Day 1.” (opens the source at this quote in a new tab)

Key ocular exclusion criteria

“Central subfield thickness (CST) >350 micrometer (mcm) in the study eye at the Screening Visit or Day 1.” (opens the source at this quote in a new tab)
“Previous treatment with intravitreal corticosteroid injection or device implantation in the study eye.” (opens the source at this quote in a new tab)

Key systemic exclusion criteria

“Myocardial infarction within 6 months prior to screening or New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled atrial fibrillation, uncontrolled angina, cardiomyopathy, ventricular arrhythmias or other cardiac conditions which, in the judgment of the investigator, could make the subject inappropriate for entry into this study.” (opens the source at this quote in a new tab)
“Glycated hemoglobin (HbA1c) greater than 7% at the Screening Visit.” (opens the source at this quote in a new tab)

Treatment arms

Arm	Quoted record
Aflibercept 2 mg	“Subjects received aflibercept 2 mg intravitreal injection on Day 1 and at Week 4 followed by intravitreal injection of aflibercept 2 mg and sham injection at Week 8 and then aflibercept 2 mg intravitreal injection once every 8 weeks up to Week 56.”
EYP-1901 2060 mcg	“Subjects received aflibercept 2 mg intravitreal injection on Day 1 and at Week 4 followed by intravitreal injection of aflibercept 2 mg and EYP-1901 2060 mcg injection at Week 8 and then intravitreal sham injection once every 8 weeks up to Week 56.”
EYP-1901 3090 mcg	“Subjects received aflibercept 2 mg intravitreal injection on Day 1 and at Week 4 followed by intravitreal injection of aflibercept 2 mg and EYP-1901 3090 mcg injection at Week 8 and then intravitreal sham injection once every 8 weeks up to Week 56.”

Relation of the phase 2 doses to the phase 3 dose

“EYP-1901 dosing likely 1 or 2 inserts (vs 2 or 3 in DAVIO 2)” (opens the source at this quote in a new tab)

“The dose investigated in phase 3 trials is 2.7 mg (two inserts of 1.343 mg each) administered in a single injection.” (opens the source at this quote in a new tab)

Primary endpoint

“Average Change in Best Corrected Visual Acuity (BCVA) From Baseline Averaged Over Weeks 28 and 32” (opens the source at this quote in a new tab)

Noninferiority margin

“The lower limit of the non-inferiority margin is defined as a -4.5 letters by the FDA with 5 letters representing one line on the eye chart.” (opens the source at this quote in a new tab)

Secondary endpoints

“Secondary endpoints include safety, change in CST as measured by OCT, the number of eyes that remain free of supplemental anti-VEGF injections, and number of aflibercept injections in each group.” (opens the source at this quote in a new tab)

Post hoc BCVA time-in-range analysis

“TIR was defined as the cumulative duration in days between visits during which the BCVA absolute letter score remained at or above the threshold” (opens the source at this quote in a new tab)
“≥ 69 letters (~20/40 SE, minimum driving requirement in most US states)” (opens the source at this quote in a new tab)

Planned and enrolled participants

“Originally designed to enroll 144 patients, the trial enrolled 160 patients in total due to strong investigator and patient interest.” (opens the source at this quote in a new tab)

“A total of 161 subjects were randomized in the study.” (opens the source at this quote in a new tab)

Participants by analysis population

Population	Aflibercept 2 mg	EYP-1901 2060 mcg	EYP-1901 3090 mcg
Started	“54”	“53”	“54”
Baseline and primary endpoint analysis (full analysis set)	“54”	“50”	“52”

Full analysis and safety sets as registered

“Full Analysis Set (FAS) included all randomized subjects who received at least 1 dose of study treatment.” (opens the source at this quote in a new tab)
“The Safety analysis set included all subjects who received at least 1 dose of study treatment.” (opens the source at this quote in a new tab)

Full analysis set as presented at congresses

“Values reflect baseline characteristics of Full Analysis Set (n=156), defined as patients who received both Day 1 and Week 8 treatments.” (opens the source at this quote in a new tab)

Participants excluded from the full analysis set

“One patient was randomized but later determined to be a screen failure and never received treatment.” (opens the source at this quote in a new tab)
“Five patients (3 in the EYP-1901 2 mg group and 2 in the EYP-1901 3 mg group) did not receive their Week 8 treatment.” (opens the source at this quote in a new tab)

Primary analysis model

“Mixed Model for Repeated Measures (MMRM)” (opens the source at this quote in a new tab)

Handling of missing visit data in supplement-free analyses

“Response at each visit calculated for only patients with nonmissing data at that visit.” (opens the source at this quote in a new tab)

Median time to first supplemental injection: censoring

“The upper limit of the 95% confidence interval for the median was not available due to an insufficient number of observed events (ie, the first supplemental aflibercept injections) occurring after the median time point.” (opens the source at this quote in a new tab)

Disposition through week 56

Milestone or reason	Aflibercept 2 mg	EYP-1901 2060 mcg	EYP-1901 3090 mcg
Started	“54”	“53”	“54”
Completed	“52”	“47”	“52”
Not completed	“2”	“6”	“2”
Adverse event: ocular, study eye	“0”	“1”	“0”
Adverse event: non-ocular	“0”	“1”	“0”
Lost to follow-up	“1”	“0”	“0”
Protocol deviation	“0”	“2”	“0”
Withdrawal by subject	“1”	“0”	“1”
Death	“0”	“2”	“0”
Discontinued study without receiving study drug	“0”	“0”	“1”

Discontinuations up to week 32

“Patient discontinuation up to week 32 was low at 4%.” (opens the source at this quote in a new tab)

Demographics: full analysis set

Characteristic	Aflibercept 2 mg, 54 participants	EYP-1901 2060 mcg, 50 participants	EYP-1901 3090 mcg, 52 participants
Age, mean (SD), years	“75.9(7.59)”	“76.4(6.66)”	“75.4(7.19)”
Female	“29”	“32”	“35”
White	“53”	“50”	“51”

Ocular characteristics and prior treatment: full analysis set

Characteristic	EYP-1901 2 mg, 50 participants	EYP-1901 3 mg, 52 participants	Aflibercept every 8 weeks, 54 participants
BCVA, mean (range), letters	“73.9 (52–84)”	“74.9 (46–85)”	“73.4 (41–85)”
CST, mean (range), µm	“264.5 (192–400)”	“262.9 (186–345)”	“265.7 (178–348)”
Duration of neovascular AMD, mean (range), years	“2.0 (0.1–7.9)”	“2.2 (0.2–10.8)”	“2.2 (0.2–20.2)”
Anti-VEGF injections per 12 months, normalized mean (range)	“9.8 (2–13)”	“10.0 (2–13)”	“9.5 (2–13)”

Summary: DAVIO 2 efficacy through week 56

DAVIO 2 randomized 161 participants; the full analysis set included 156 (54 aflibercept 2 mg every 8 weeks, 50 EYP-1901 2060 mcg, 52 EYP-1901 3090 mcg). For the primary endpoint (BCVA change averaged over weeks 28 and 32), the registry reports least-squares mean changes of 1.17, 1.05, and 0.87 letters, with differences versus aflibercept of -0.12 letters (95% CI, -2.48 to 2.24) for 2060 mcg and -0.31 letters (95% CI, -2.63 to 2.02) for 3090 mcg; both lower confidence limits were above the -4.5-letter noninferiority margin. EyePoint's topline release reported differences of -0.3 and -0.4 letters. At week 56, mean BCVA change was 1.1 letters with aflibercept, 0.3 letters with 2060 mcg, and -1.9 letters with 3090 mcg. Up to week 32, 62.5% and 63.5% of EYP-1901 participants received no supplemental aflibercept, compared with 94.3% of aflibercept participants; at week 56, the proportions were 42.6%, 46.2%, and 82.7%. The normalized number of aflibercept injections through week 56 was 3.45 and 3.36 in the EYP-1901 arms and 6.33 in the aflibercept arm.

Primary endpoint: BCVA change averaged over weeks 28 and 32

Statistic	Aflibercept 2 mg	EYP-1901 2060 mcg	EYP-1901 3090 mcg
Least-squares mean change, letters	“1.17”	“1.05”	“0.87”
Least-squares mean difference vs aflibercept, letters	Not applicable	“-0.12”	“-0.31”
95% CI lower limit	Not applicable	“-2.48”	“-2.63”
95% CI upper limit	Not applicable	“2.24”	“2.02”
P value	Not applicable	“0.919”	“0.795”

Primary endpoint: company-reported topline result

“Statistical non-inferiority in change in BCVA (at a confidence interval of 95%) compared to aflibercept control, at weeks 28 and weeks 32 combined. The 2mg and 3mg doses were only -0.3 and -0.4 letters different, respectively, versus on-label aflibercept.” (opens the source at this quote in a new tab)

BCVA mean change from baseline at weeks 32 and 56

Visit	Aflibercept 2 mg	EYP-1901 2060 mcg	EYP-1901 3090 mcg
Baseline, mean letters	“73.4”	“73.9”	“74.9”
Week 32, mean change, letters	“1.6”	“1.0”	“0.8”
Week 56, mean change, letters	“1.1”	“0.3”	“-1.9”

Categorical BCVA change at weeks 32 and 56

Category, percentage of participants	Aflibercept 2 mg, 53 participants	EYP-1901 2060 mcg, 48 participants	EYP-1901 3090 mcg, 52 participants
Week 32, gain of 5 or more letters	“34.0”	“25.0”	“21.2”
Week 32, loss of 5 or more letters	“13.2”	“20.8”	“11.5”
Week 32, loss of 15 or more letters	“1.9”	“0”	“1.9”
Week 56, gain of 5 or more letters	“32.7”	“23.4”	“15.4”
Week 56, loss of 5 or more letters	“23.1”	“23.4”	“32.7”
Week 56, loss of 10 or more letters	“11.5”	“10.6”	“13.5”
Week 56, loss of 15 or more letters	“7.7”	“4.3”	“3.8”

Categorical BCVA change at month 7/8: company-reported

“No EYP-1901 patients had loss of ≥15 letters” (opens the source at this quote in a new tab)

Participants without supplemental aflibercept

Visit, percentage of participants	Aflibercept 2 mg, 53 participants	EYP-1901 2060 mcg, 48 participants	EYP-1901 3090 mcg, 52 participants
Up to week 32	“94.3”	“62.5”	“63.5”
Up to week 56	“82.7”	“42.6”	“46.2”

Median time to first supplemental aflibercept injection after week 8

Statistic	EYP-1901 2060 mcg, 50 participants	EYP-1901 3090 mcg, 52 participants
Median, weeks	“37.00”	“40.79”
95% CI	“(20.14 to NA)”	“(20.00 to NA)”

Normalized aflibercept injections, including loading doses

Visit, mean (SD)	Aflibercept 2 mg, 54 participants	EYP-1901 2060 mcg, 50 participants	EYP-1901 3090 mcg, 52 participants
Week 32	“3.23(0.357)”	“2.06(0.583)”	“2.13(0.747)”
Week 56	“6.33(0.754)”	“3.45(1.738)”	“3.36(1.854)”

Treatment burden compared with the pre-trial period

“89% and 85% reduction in treatment burden, respectively, for the 2mg and 3mg EYP-1901 doses.” (opens the source at this quote in a new tab)

“EYP-1901 reduced treatment burden by ≥80% over 12 months vs pre-trial treatment” (opens the source at this quote in a new tab)
“63% at 6 months after EYP-1901 dosing” (opens the source at this quote in a new tab)
“44% at 12 months after EYP-1901 dosing” (opens the source at this quote in a new tab)
“About one-third of aflibercept q8W arm patients met criteria and received supplemental treatment” (opens the source at this quote in a new tab)

Reasons for supplemental injections up to week 32

“24% (12/50) of EYP-1901 2 mg patients” (opens the source at this quote in a new tab)
“31% (16/52) of EYP-1901 3 mg patients” (opens the source at this quote in a new tab)
“Received supplemental injections per prespecified criteria” (opens the source at this quote in a new tab)

“12% (6/50) of EYP-1901 2 mg patients” (opens the source at this quote in a new tab)
“6% (3/52) of EYP-1901 3 mg patients” (opens the source at this quote in a new tab)
“Received supplemental injections while never meeting prespecified criteria” (opens the source at this quote in a new tab)
“SRF increased: Accounted for half of injections not meeting any criteria” (opens the source at this quote in a new tab)

Anatomic outcomes at weeks 32 and 56

Measure	Aflibercept 2 mg	EYP-1901 2060 mcg	EYP-1901 3090 mcg
CST, baseline mean, µm	“265.7”	“264.5”	“262.9”
CST, week 32 mean change, µm	“5.4”	“17.8”	“10.6”
CST, week 56 mean change, µm	“8.1”	“12.2”	“16.7”
No detectable intraretinal fluid in the central subfield, week 32, %	“62.3”	“52.1”	“51.9”
No detectable intraretinal fluid in the central subfield, week 56, %	“59.6”	“59.6”	“51.9”

Subgroup: eyes without supplemental treatment through month 8

“Among patients who did not receive supplemental injections, BCVA results were similar across arms” (opens the source at this quote in a new tab)
“Among patients who did receive supplemental injections, BCVA was stable with EYP-1901 through Month 8” (opens the source at this quote in a new tab)

Arm	Supplement-free subgroup size
EYP-1901 3 mg	“EYP-1901 3 mg, n=33”
EYP-1901 2 mg	“EYP-1901 2 mg, n=30”
Aflibercept every 8 weeks	“Aflibercept q8W, n=46”

Subgroup: supplement-free eyes, BCVA difference versus aflibercept at month 7/8

Arm	Mean change in BCVA vs aflibercept
EYP-1901 2 mg	“DURAVYU 2mg +0.6”
EYP-1901 3 mg	“DURAVYU 3mg +0.1”

Post hoc time-in-range analysis through week 32

“One dose of EYP-1901 3 mg maintained vision ≥ 69 letters for 28 of 32 weeks” (opens the source at this quote in a new tab)
“In supplement-free patients, BCVA TIR results were similar across arms” (opens the source at this quote in a new tab)

Participants with treatment-emergent adverse events through week 56

Category	Aflibercept 2 mg, 54 participants	EYP-1901 2060 mcg, 50 participants	EYP-1901 3090 mcg, 52 participants
Any TEAE, study eye	“30”	“30”	“30”
Any TEAE, fellow eye	“21”	“11”	“20”
Any TEAE, systemic	“40”	“28”	“39”
Serious TEAE, study eye	“2/54 (3.70%)”	“0/50 (0.00%)”	“4/52 (7.69%)”
Serious TEAE, fellow eye	“1/54 (1.85%)”	“0/50 (0.00%)”	“0/52 (0.00%)”
Serious TEAE, systemic	“6/54 (11.11%)”	“6/50 (12.00%)”	“9/52 (17.31%)”
All-cause mortality, systemic	“0/54 (0.00%)”	“2/50 (4.00%)”	“0/52 (0.00%)”

Study eye serious adverse events: endophthalmitis

Event, study eye	Aflibercept 2 mg	EYP-1901 2060 mcg	EYP-1901 3090 mcg
Endophthalmitis	“2/54 (3.70%)”	“0/50 (0.00%)”	“3/52 (5.77%)”
Non-infectious endophthalmitis	“0/54 (0.00%)”	“0/50 (0.00%)”	“1/52 (1.92%)”

“For the events of endophthalmitis in the Serious Adverse Events (SAE) table, none were considered related to EYP-1901. In the aflibercept treatment group, these events were considered related to the injection procedure or were not treatment-related. In the EYP-1901 treatment group, these events were considered related to the supplemental injection procedure (with aflibercept), the paracentesis for aqueous humor collection, or were not treatment-related.” (opens the source at this quote in a new tab)

Study eye serious adverse events: investigator-reported timing (November 2023 data cut)

“Retinal detachment at week 1; one week after initial aflibercept injection, prior to EYP-1901 injection” (opens the source at this quote in a new tab)
“Bacterial endophthalmitis at week 32; two days after anterior chamber paracentesis in a patient using CPAP” (opens the source at this quote in a new tab)
“Non-infectious endophthalmitis at week 29; seven days after aflibercept injection” (opens the source at this quote in a new tab)
“Retinal tears at week 36; four weeks after aflibercept injection” (opens the source at this quote in a new tab)

Selected non-serious adverse events

Event	Aflibercept 2 mg	EYP-1901 2060 mcg	EYP-1901 3090 mcg
Visual acuity reduced, study eye	“3/54 (5.56%)”	“1/50 (2.00%)”	“8/52 (15.38%)”
Vitreous floaters, study eye	“1/54 (1.85%)”	“2/50 (4.00%)”	“6/52 (11.54%)”
Hypertension, systemic	“4/54 (7.41%)”	“2/50 (4.00%)”	“7/52 (13.46%)”

Company-reported safety findings through end of study

“No EYP-1901–related ocular SAEs or systemic SAEs” (opens the source at this quote in a new tab)
“No insert migration into the anterior chamber” (opens the source at this quote in a new tab)
“No cases of retinal occlusive vasculitis” (opens the source at this quote in a new tab)
“Six participants with ocular study eye SAEs – none deemed related to EYP-1901” (opens the source at this quote in a new tab)

Systemic and ocular exposure to EYP-1901

Matrix and visit	EYP-1901 2060 mcg	EYP-1901 3090 mcg
Plasma, week 20, mean, pg/mL	“23.206”	“27.121”
Plasma, week 56, mean, pg/mL	“7.733”	“10.392”
Aqueous humor, week 20, mean, ng/mL	“17.426”	“25.066”
Aqueous humor, week 32, mean, ng/mL	“11.890”	“19.813”

Summary

DAVIO 2 was a phase 2 trial with 50 to 54 participants per arm in the full analysis set, conducted at 39 sites in the United States, with 154 of 156 participants (98.7%) reported as White. Eligibility required a documented anatomic response to prior anti-VEGF therapy, at least 2 anti-VEGF injections in the prior 6 months, and CST of 350 µm or less, so treatment-naive eyes and eyes with greater baseline exudation were not studied. All arms received aflibercept loading at day 1, week 4, and week 8, including an aflibercept injection given with the EYP-1901 insert at week 8. The tested doses (2060 mcg and 3090 mcg, single administration) differ from the 2.7-mg dose given every 6 months in phase 3. The primary endpoint was measured 20 to 24 weeks after insert administration; the week 56 BCVA, supplement-free, and injection-count outcomes are descriptive secondary outcomes without reported hypothesis tests. Company presentations defined the full analysis set as participants who received both day 1 and week 8 treatments, whereas the registry describes it as participants who received at least 1 dose, and company-reported differences for the primary endpoint (-0.3 and -0.4 letters) differ from the registry least-squares differences (-0.12 and -0.31 letters). Several subgroup and time-in-range analyses were post hoc. No peer-reviewed full publication of DAVIO 2 was identified; most results come from sponsor press releases, sponsor-funded congress presentations, and the registry record.