Outlook Therapeutics, Inc. has resubmitted its Biologics License Application (BLA) for its investigational wet age-related macular degeneration (AMD) treatment: ONS-5010 (bevacizumb-vikg).
This news follows less than 2 months after the biopharmaceutical company was issued a second company response letter (CRL) from the FDA in regards to its second BLA submission attempt.
First, refresh me on this therapeutic.
As we’ve previously (and continuously) reported, Outlook’s candidate is formulated with bevacizumab, a recombinant humanized monoclonal antibody (mAb).
- Generally speaking, the mAB works by identifying and binding to vascular endothelial growth factor (VEGF) to prevent the formation, growth, and spread of potential tumors.
And in wet AMD: This rundown explains how bevacizumab works in ONS-5010 to neutralize the VEGF’s biologic activity and treat the retinal disease.
How is it delivered?
Via an intravitreal (IVT) injection administered on a monthly basis.
And its performance in clinical trials?
The formulation was originally evaluated in three studies:
- Two registrational trials (NORSE ONE and NORSE TWO)
- One open-label trial (NORSE THREE)
See here for details on these.
You said “originally” … does that mean there were more studies?
Following that initial BLA rejection, yes: NORSE EIGHT.
- Click here to learn about that randomized, controlled, parallel-group, masked, noninferiority study (including positive 12-week findings reported earlier this year that found ONS-5010 demonstrated noninferiority to ranibizumab).
Now to ONS-5010’s quest for regulatory approval …
Interestingly enough, ONS-5010 has already received regulatory clearance in the European Union and United Kingdom under the name LYTENAVA.
But in the United States: The formulation’s first two BLAs went down like this:
- A CRL issued in August 2023 following an initial BLA submission in 2022
- Check out our prior reporting on the candidate’s ongoing saga with the FDA for specific reasoning behind the agency’s rejections.
- A second CRL was issued in September 2025 following a second BLA acceptance in April 2025
What was the reason for the agency’s most recent CRL?
Despite the BLA submission including—as requested by the FDA—additional clinical data from the NORSE EIGHT trial plus chemistry, manufacturing, and controls (CMC) information, the agency wanted more confirmatory evidence of ONS-5010’s efficacy.
See our coverage for more on this.
And how does this newest (third?) submission address these issues?
No specifics were provided.
In announcing this news, Outlook shared that the resubmission came after the company received “the official minutes from the FDA Type A meeting” that was conducted in September.
- To note: A Type A meeting with the FDA is held at a company’s request when there’s a stalled development or clinical hold (such as a rejected BLA, in this instance).
As CEO Bob Jahr stated, following the company’s “productive” meeting with the FDA, “We believe this resubmission will resolve the outstanding issue highlighted in the CRL we received in August.”
So … now we wait?
Yup, now we wait. The FDA is expected to provide a response (either an acceptance or rejection) to this third BLA within 60 days of its submission.