An Ophthalmic Drug Used for 20 Years Through “External Compounding” Finally Has an FDA-Approved Version

Bevacizumab has long been familiar in the treatment of wet age-related macular degeneration. What is unusual is that it has primarily been used off-label for intravitreal injection after pharmacies divided the intravenous cancer formulation into smaller doses. On July 24, the U.S. Food and Drug Administration (FDA) approved Outlook Therapeutics’ Lytenava (bevacizumab-vikg), giving a bevacizumab formulation manufactured specifically for intravitreal injection authorization for the U.S. market for the first time.

Wet macular degeneration results from the growth and leakage of abnormal blood vessels beneath the retina and can rapidly damage central vision. Lytenava inhibits vascular endothelial growth factor A (VEGF-A), reducing new blood vessel formation and vascular permeability. The approved dose is 1.25 mg per eye, administered by intravitreal injection approximately every 28 days. The company expects to make it available in the United States by the end of 2026.

What this approval changes first is the product’s regulatory identity, rather than its mechanism of action. Ophthalmologists have more than 20 years of experience using repackaged bevacizumab, but the original product was designed for intravenous cancer treatment. Lytenava, by contrast, has an ophthalmology-specific manufacturing process, single-use vials, and formal prescribing information, while its manufacturing and quality systems are also subject to ongoing FDA oversight. Whether it can replace existing repackaged products will still depend on pricing, insurance reimbursement, and healthcare institutions’ purchasing decisions.

The efficacy evidence presents two different pictures. In the randomized NORSE TWO trial, after 11 months of treatment, 41.7% of patients in the Lytenava group gained at least 15 letters on a visual acuity chart, compared with 23.1% in the ranibizumab group. However, dosing frequency differed between the two groups: Lytenava was administered monthly, while the comparator was administered monthly for the first three months and then once every three months. The results therefore cannot be interpreted simply as showing the direct superiority or inferiority of the two drugs under the same treatment regimen.

Another trial, NORSE EIGHT, enrolled 400 people and used the same once-every-four-weeks dosing schedule, but it did not meet the prespecified noninferiority criterion. At week 8, the mean improvements in visual acuity with Lytenava and ranibizumab were 3.3 and 4.5 letters, respectively; the lower bound of the 95% confidence interval for the adjusted difference between the two groups exceeded the trial’s specified margin. The FDA ultimately granted approval, but this negative result reminds the medical community that a product’s formal ophthalmic status does not mean it has been proven noninferior to existing therapies in every comparative setting.

The safety risks largely remain consistent with the known issues associated with intravitreal injections and anti-VEGF therapy, including endophthalmitis, retinal detachment, increased intraocular pressure after injection, and potential arterial thromboembolic events. The most common adverse reaction listed in the prescribing information is conjunctival hemorrhage. The product must not be used in patients with ocular or periocular infections, active intraocular inflammation, or hypersensitivity to bevacizumab products. For clinical practice, the real test will be whether a product with more standardized manufacturing and labeling can, at an acceptable cost, change long-established prescribing practices despite inconsistent efficacy evidence.