Review section

Field	Value
Drug	Lytenava (bevacizumab-vikg)
Indication reviewed	Neovascular age-related macular degeneration
Therapeutic category	Ophthalmic vascular endothelial growth factor (VEGF) inhibitors (intravitreal anti-VEGF monoclonal antibody)
Manufacturer	Outlook Therapeutics
Regulatory status	Approved July 24, 2026
Data as of	September 28, 2026
Prepared by	To be completed by the reviewing plan
Review status	Draft for pharmacy and therapeutics committee review

Indications

Table 1. FDA-approved indications

Indications	Lytenava (bevacizumab-vikg)
“treatment of patients with neovascular (wet) age-related macular degeneration (nAMD)”	✓

Trial in which efficacy was established

“The efficacy of LYTENAVA for the treatment of neovascular (wet) age-related macular degeneration (nAMD) was demonstrated in a randomized, multi-center, masked, active-controlled study (NORSE TWO – NCT03834753).” (opens the prescribing information at this quote)

Age limit of the indication

“The safety and effectiveness of LYTENAVA in pediatric patients have not been established.” (opens the prescribing information at this quote)

Pharmacokinetics

Table 2. Pharmacokinetic parameters

Generic Name(s)	Bioavailability	Protein Binding	Metabolism	Excretion	Half-Life
Bevacizumab-vikg	Not reported	Not reported	Not reported	Not reported	Not reported

Systemic exposure after intravitreal injection

“Following intravitreal administration of LYTENAVA, the systemic exposure to bevacizumab-vikg is minimal.” (opens the prescribing information at this quote)
“In 14 subjects who received a single 1.25 mg dose of LYTENAVA, the serum bevacizumab-vikg concentration was assessed up to Day 4. The serum bevacizumab-vikg concentrations gradually increased over time, so the highest concentrations observed were approximately at Day 4 (the last collection time) ranging from 33 to 270 ng/mL, which was <1% of the Cmax after intravenous infusion of 2 mg/kg bevacizumab-vikg. However, due to the limited sample collection, Cmax or AUC could not be adequately characterized.” (opens the prescribing information at this quote)

Immunogenicity

“In a 52-week study, a total of 14 subjects who received LYTENAVA and were subsequently evaluated for immunogenicity did not show detectable ADA at any timepoint but the ADA assay sensitivity data in the presence of free drug was insufficient. However, due to the minimal systemic exposure to LYTENAVA following intravitreal injection, the risk of immunogenicity is not expected to be clinically significant.” (opens the prescribing information at this quote)

Drug interactions

Table 3. Major drug interactions

No evidence found.

Contents of the prescribing information, which list no drug interactions section

“6 ADVERSE REACTIONS 6.1 Clinical Trials Experience 8 USE IN SPECIFIC POPULATIONS” (opens the prescribing information at this quote)
“Sections or subsections omitted from the full prescribing information are not listed.” (opens the prescribing information at this quote)

Adverse drug events

Table 4. Adverse drug events reported in 1% or more of patients across five clinical trials

Adverse Event	Lytenava 1.25 mg (N = 601), %	Ranibizumab 0.5 mg (N = 345), %
Conjunctival hemorrhage	“4%”	“3%”
Eye pain	“2%”	“1%”
Vitreous floaters	“2%”	“1%”

Safety population and comparator in Table 4

“The data described below reflect exposure to LYTENAVA in 601 patients, in five clinical trials” (opens the prescribing information at this quote)
“Table 1 shows the most common ocular adverse reactions in LYTENAVA treated patients compared with ranibizumab 0.5 mg.” (opens the prescribing information at this quote)

Less common ocular adverse reactions

“Less common ocular adverse reactions reported in the study eye in <1% of patients treated with LYTENAVA were corneal abrasion, dry eye, eye irritation, and intraocular pressure increased.” (opens the prescribing information at this quote)

Warnings and precautions

“Intravitreal injections have been associated with endophthalmitis and retinal detachments. Proper aseptic injection technique should always be used when administering LYTENAVA.” (opens the prescribing information at this quote)
“Increases in intraocular pressure have been noted post-injection (up to 60 minutes) while being treated with LYTENAVA.” (opens the prescribing information at this quote)
“Although there was a low rate of arterial thromboembolic events (ATEs) observed in the LYTENAVA clinical trials, there is a potential risk of ATEs following intravitreal use of VEGF inhibitors. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause).” (opens the prescribing information at this quote)

Contraindications

“LYTENAVA is contraindicated in patients with ocular or periocular infections.” (opens the prescribing information at this quote)
“LYTENAVA is contraindicated in patients with active intraocular inflammation.” (opens the prescribing information at this quote)
“LYTENAVA is contraindicated in patients with known hypersensitivity to bevacizumab products or any of the ingredients in LYTENAVA. Hypersensitivity reactions may manifest as severe intraocular inflammation.” (opens the prescribing information at this quote)

Dosing and administration

Table 5. Usual dosing regimens

Generic Name	Usual Adult Dose	Usual Pediatric Dose	Availability
Bevacizumab-vikg	“The recommended dose for LYTENAVA is 1.25 mg (0.05 mL of 25 mg/mL) administered by intravitreal injection once monthly (approximately 28 days).”“LYTENAVA must only be administered by a qualified physician.”	“The safety and effectiveness of LYTENAVA in pediatric patients have not been established.”	“Injection: 1.25 mg (0.05 mL of 25 mg/mL) colorless to light brown, opalescent solution for intravitreal injection in a single-dose vial.”“Each carton (NDC 82491-025-10) contains LYTENAVA 1.25 mg (0.05 mL of 25 mg/mL bevacizumab-vikg solution) in a single-dose glass vial with a BLUE CAP.”

See the current prescribing information for full details.

Devices, preparation, and single-eye use

“A 5-micron sterile filter needle (18-gauge x 1½-inch), a 1-mL syringe (with marking to measure 0.05 mL), and a 30-gauge x ½-inch sterile injection needle are needed.” (opens the prescribing information at this quote)
“The glass vial is for one-time use in one eye only.” (opens the prescribing information at this quote)
“Each single-dose vial should only be used for the treatment of a single eye. If the contralateral eye requires treatment, a new vial should be used and the sterile field, syringe, gloves, drapes, eyelid speculum, filter needle, and injection needles should be changed before LYTENAVA is administered to the other eye.” (opens the prescribing information at this quote)

Injection procedure and post-injection monitoring

“The intravitreal injection procedure should be carried out under controlled aseptic conditions, which include the use of sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide should be given prior to injection.” (opens the prescribing information at this quote)
“Prior to and 30 minutes following the intravitreal injection, patients should be monitored for elevation in intraocular pressure using tonometry.” (opens the prescribing information at this quote)

Effectiveness

Table 6. Comparative clinical trials

Study and Drug Regimen	Study Design and Demographics	Study Size and Duration	End Points	Results
NORSE TWO (NCT03834753): “randomized to LYTENAVA 1.25 mg (N=113) administered once monthly for 1 year or ranibizumab 0.5 mg (N=115) administered once monthly for 3 months (Days 0, 30, and 60) followed by once every 3 months for 1 year (Days 150 and 240)”	“a randomized, multi-center, masked, active-controlled study”“adult patients with nAMD”“Patient ages ranged from 54 to 98 years, with a median age of 79 years.”	“LYTENAVA 1.25 mg (N=113)”“ranibizumab 0.5 mg (N=115)”“once monthly for 1 year”	Primary: “The primary efficacy endpoint was the proportion of patients who gained ≥ 15 Best Corrected Visual Acuity (BCVA) letters from baseline to Month 11 as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score.”Secondary: “The pre-specified secondary efficacy endpoint of mean change in BCVA from baseline to Month 11”	Patients gaining ≥15 letters, n/N (%): Lytenava “45/108 (41.7)”Ranibizumab “24/104 (23.1)”Risk difference: “0.1859”95% CI: “0.0442, 0.3086”“The difference observed between the study drug groups was significant, in favor of LYTENAVA”Mean change in BCVA: “favored LYTENAVA once monthly compared to ranibizumab administered once monthly for 3 months then every 3 months”
NORSE EIGHT (NCT06190093): “randomized (1:1) to LYTENAVA 1.25 mg or ranibizumab 0.5 mg, administered every 4 weeks for 3 total doses (Day 0, Week 4, and Week 8)”	“a multicenter, randomized, masked, controlled study”	“400 adult patients with nAMD”“every 4 weeks for 3 total doses (Day 0, Week 4, and Week 8)”	Primary: “The primary efficacy endpoint was the mean change in baseline BCVA as measured by ETDRS score at Week 8 using a non-inferiority (NI) margin of -3.5 letters.”	“At Week 8, the LYTENAVA group had a mean increase in BCVA of 3.3 compared to a mean increase of 4.5 in the ranibizumab group. The LS mean difference and 95% CI was -2.3 (-4.0, -0.5).”“NORSE EIGHT did not meet its pre-specified NI margin of -3.5 letters in mean change from baseline BCVA at Week 8 compared to ranibizumab.”“LYTENAVA showed an increase from baseline in BCVA at Week 12 consistent with NORSE TWO.”

Abbreviations: BCVA=best corrected visual acuity; CI=confidence interval; ETDRS=Early Treatment Diabetic Retinopathy Study; LS=least squares; nAMD=neovascular age-related macular degeneration; NI=non-inferiority

Age of patients in the Phase 3 trials

“In the three completed Phase 3 clinical studies, approximately 70% (238/341) of patients treated with LYTENAVA were ≥ 65 years of age and approximately 47 % (160/341) were ≥ 75 years of age. No overall differences in efficacy or safety were seen with increasing age in these studies” (opens the prescribing information at this quote)

NORSE TWO eligibility, comparator regimen, p-value, and mean change in visual acuity, from the trial publication, which the prescribing information does not state

“Treatment-naïve nAMD patients aged 50 years and older with a best-corrected distance visual acuity (BCVA) of 25 to 67 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and evidence of disease activity were included.” (opens the source at this quote in a new tab)
“Patients randomized to ONS-5010 received monthly intravitreal doses of 1.25 mg of ONS-5010, bevacizumab-vikg (Outlook Therapeutics) for 12 months. Patients randomized to ranibizumab received 0.50 mg of ranibizumab on days 0, 30, 60, 150, and 240 based on the PIER study dosing regimen.” (opens the source at this quote in a new tab)
“Respectively, 41.7% and 23.1% of patients gained ≥ 15 letters (3 lines) of visual acuity, with a risk difference of 0.1859 [95% CI = 0.0442, 0.3086]; P = 0.0052. The change in BCVA from baseline to 11 months was found to be 11.2 ± 12.19 and 5.8 ± 14.80 ETDRS letters, respectively.” (opens the source at this quote in a new tab)

NORSE EIGHT Week 12 comparison, from the sponsor, which the prescribing information does not quantify

“The difference in mean BCVA between ONS-5010 and ranibizumab was -1.009 letters (95% confidence interval, -2.865, 0.848), meeting the noninferiority margin at Month 3 (p=0.0043)” (opens the source at this quote in a new tab)