Outlook Therapeutics announced the FDA has accepted its resubmission of a biologics license application (BLA) for ONS-5010 (bevacizumab-vikg), an ophthalmic formulation intended for the treatment of wet age-related macular degeneration (AMD).
Let’s start with Outlook.
The New Jersey-based biopharmaceutical company’s sole purpose involves developing and bringing to the U.S. commercial market the first FDA-approved bevacizumab formulation targeting wet AMD and two other retinal disease indications:
- Diabetic macular edema (DME)
- Branch retinal vein occlusion (BRVO)
And notably: The company has already secured regulatory approval for bevacizumab in the European Union (EU) and United Kingdom (UK) for this eyedrop—making it the first bevacizumab ophthalmic formulation in those regions.
Tell me about this solution.
Also referred to as LYTENAVA (in the EU and UK), ONS-5010 is formulated to be delivered via intravitreal (IVT) injection in a monthly dosing schedule.
Zeroing in on its active ingredient: Bevacizumab is a recombinant humanized monoclonal antibody (mAb).
- What it does: Selectively binds with a high affinity all isoforms (similar proteins with different genes) of human vascular endothelial growth factor (VEGF).
Explain how ONS-5010 works.
The formulation’s mechanism of action (MOA) is divided into two parts.
During the injection: The mAB neutralizes the biologic activity of the VEGF by blocking it from binding to receptors (which are located on the endothelial cell surface).
Following injection: This leads to a reduction in:
- Endothelial cell proliferation
- Vascular leakage
- New blood vessel formation in the retina
Got it. So talk to me about why this is a "resubmission."
This BLA acceptance is redemption for Outlook after the FDA sent a company response letter (CRL) and declined to approve its previous BLA submission for OSN-5010 in August 2023.
- The reasoning behind the rejection: Several issues were highlighted (see here).
And keep in mind: Prior to that rejection, Outlook had submitted a BLA in March 2022 before voluntarily withdrawing it in May 2022 to provide additional info requested by the FDA, resubmitting it in August 2022, after which it was accepted in October 2022.
Now to the subject at hand: What is this new BLA based on?
To start: Additional CMC information the FDA requested from the company back in August 2023 (in its CRL).
As a refresher: The agency had informed Outlook that to meet the FDA’s requirement for a “second adequate and well-controlled clinical trial” of ONS-5010, it would need to conduct a “non-inferiority study evaluating ONS-5010 versus ranibizumab in a 12 week study of treatment naïve patients with a primary efficacy endpoint at 8 weeks.”
- Enter in: the NORSE EIGHT clinical trial, a randomized, controlled, parallel-group, masked, noninferiority study (NCT06190093)
Talk about that clinical study.
To note: While ONS-5010 was previously studied in three trials (NORSE ONE, TWO, and THREE), efficacy and safety data included in the NORSE EIGHT study were key to this updated BLA submission.
A quick look at its setup:
- Participants: Approximately 400 (aged 50+) newly diagnosed with wet AMD
- Dosings: 1:1 randomization to receive IV-administered injections at Day 1, Weeks 4 and 8
- 1.25 mg ONS-5010
- 0.5 mg ranibizumab
- Primary outcome measure: Effectiveness of IVT injections of ONS-5010 versus ranibizumab to prevent vision loss (baseline to Week 8)
And the positive findings?
Reported in February 2025, ONS-5010 demonstrated noninferiority to ranibizumab at Week 12—with a mean difference between the two of:
- 1.009 BCVA letters with a 95% confidence interval of (-2.865, 0.848)
Notably:
- ONS-5010 was “generally well-tolerated” with overall ocular adverse events comparable to that of ranibizumab.
- Safety results demonstrated across the study’s entire duration were consistent with those reported in previous NORSE trials, including no cases of retinal vasculitis reported in either study arm.
Definitely sounds promising … so what does this BLA acceptance mean?
The FDA has classified the BLA as a Class 2 review (a more extensive review period for BLA submissions)—giving the agency a 6-month review period (from the date of resubmission) of the application.
The resubmission date: Feb 28.
And when can we expect a decision?
The agency set a Prescription Drug User Fee Act (PDUFA) goal date of Aug. 27, 2025.
Lastly: What’s the potential significance of this formulation?
As Outlook noted: “If approved, [OSN-0150] will be branded as LYTENAVA (bevacizumab-vikg) in the United States for the treatment of wet AMD and is expected to receive 12 years of regulatory exclusivity.”
- Meaning: This exclusivity would prevent any generic versions of bevacizumab-vikg from being approved and marketed in the U.S. for that time period.