In this episode of Evidence-Based Retina, Rishi Singh, MD, discusses the new FDA label for bevacizumab (LYTENAVA) in the treatment of wet age-related macular degeneration (AMD) with Bob Jahr, CEO of Outlook Therapeutics, Inc.
Outlook Therapeutics was established over 10 years ago and initially started as a biologics/biosimilar company. About 8 years ago, the company shifted its focus toward developing a novel, approved formulation of bevacizumab (LYTENAVA) specifically for treating wet AMD.
Indications for bevacizumab
The initial approved indication for bevacizumab is for wet AMD. However, the company has Special Protocol Assessments (SPAs) in place for diabetic macular edema (DME) and retinal vein occlusion (RVO), and plans for phase 3 trials.1
According to Bob Jahr, “Bevacizumab has been foundational for many ophthalmology patients for wet AMD over the years, and over 40% of patients get treated with a bevacizumab compounded product, so what we're very excited about is providing the first [an] FDA-approved one, but also the one that's gone through the rigor of the CMC and approval process for manufacturing.”
A closer look at the NORSE clinical trials
The clinical trial program included four trials for ONS-5010 (LYTENAVA), notably the pivotal NORSE TWO and confirmatory NORSE EIGHT trials.2,3 NORSE TWO was a 12-month phase 3 study with 228 patients, comparing ONS-5010 to ranibizumab.
“NORSE TWO is our pivotal trial, which demonstrated our effects against ranibizumab over a 12-month period, which really was the foundation of our submission to the FDA.”
Results showed that at month 11, 41% of ONS-5010 patients gained ≥15 letters in best-corrected visual acuity (BCVA) compared with 23% for ranibizumab, with a mean change in BCVA of 11.2 letters versus 5.8 letters.2 Safety profiles were comparable, with ocular adverse events in 45.1% of ONS-5010 patients and 41.7% of ranibizumab patients.
In NORSE EIGHT, ONS-5010 was non-inferior to ranibizumab, with a mean difference of -1.009 BCVA letters at week 12.3 Mean BCVA improved by 5.5 letters for ONS-5010 compared to 6.5 letters for ranibizumab, and central retinal thickness changes were similar between groups.
Although ONS-5010 did not meet the week 8 non-inferiority endpoint set by the FDA's SPA, BCVA improved steadily over time. Safety was good, with ocular adverse event rates similar to ranibizumab and no retinal vasculitis reported.3
FDA and global approval status
Despite past challenges, including a few complete response letters (CRLs), LYTENAVA received FDA approval for wet AMD on July 24th.4 Commercialization is expected to start in the second half of the year, with product availability projected by the end of the year at the latest.
The company has been in Europe for a couple of years and began commercializing about a year ago. It has launched in Germany, the UK, and Austria, with plans to expand further. The European label utilizes a "treat and extend" dosing protocol, offering physicians flexibility in customization.
Key takeaways
- On July 24, 2026, LYTENAVA (bevacizumab-vikg; ONS-5010) became the first FDA-approved ophthalmic formulation of bevacizumab for wet AMD in the US.4
- In NORSE TWO, 41% of ONS-5010 patients gained ≥15 letters in BCVA at month 11 versus 23% for ranibizumab.2
- NORSE EIGHT showed non-inferiority to ranibizumab at week 12, though the week 8 endpoint set by the FDA's SPA was not met.3
- Outlook holds SPAs for DME and RVO, supporting future indication expansion beyond wet AMD.
- LYTENAVA is already commercialized in Europe using treat-and-extend dosing, and Outlook plans to invest in a pre-filled syringe program.
Closing thoughts
Outlook plans to continually invest in a pre-filled syringe program to enhance convenience for both patients and practitioners. The company is committed to ensuring broad access and affordability while adhering to a rigorous FDA-approved manufacturing process. This approach aims to eliminate the quality and compounding variability that is often associated with off-label bevacizumab.
