The FDA has accepted Outlook Therapeutics, Inc’s submission of a formal dispute resolution request (FDRR) in regard to the rejected new drug application (NDA) for ONS-5010 (LYTENAVA; bevacizumab-vikg) to treat wet age-related macular degeneration (AMD).
Lots to catch up on here …
Indeed. For the sake of brevity:
- Click here for details on this wet AMD candidate.
- See here for a look at its supporting clinical data.
Also important to keep in mind: LYTENAVA has been the subject of … not one, not two, but … three complete response letters (CRLs) following the FDA’s rejection(s) of Outlook’s three BLAs.
- Coverage on the first, second, and third (sent in in January 2026) CRLs can be found here, here, and here, respectively.
Yikes. Can the gist of those letters be summed up?
For the first two CRLs, the FDA essentially asked Outlook for more clinical data to support LYTENAVA’s submission packages.
For this third and most recent CRL: Though additional data was included, the agency said it still didn’t address the “lack of substantial evidence of effectiveness” stipulated in prior CRLs.
- See here for some background on this efficacy data the FDA is requesting.
And the company’s response to that?
Outlook essentially stated that it believes the data included in its most recent BLA submission “provides the required evidence to support approval of the (LYTENAVA)” in the U.S.
… which brings us to this update?
Indeed. The company shared that, since its December 2025 receipt of that third CRL, it has met with the FDA “on multiple occasions.”
Included among these: A formal Type A meeting, held on March 2, to address LYTENAVA’s stalled product development program; the result was Outlook’s submission of an FDRR (and another meeting with the FDA).
Can we get a refresher on what an FDRR is?
This is basically a formal, written appeal from a sponsor (such as Outlook) to the FDA when it disagrees with the federal agency’s decision or feedback and wants a formal review.
Importantly: When the sponsor is still in disagreement on the FDA’s position and the issue (such as a rejected NDA submission) remains unresolved, an FDRR is sent to the next level up the FDA command chain following the Type A meeting.
And what does it entail?
An FDRR will typically include:
- The FDA action or decision in question
- A history of meetings with the FDA (such as a Type A meeting)
- The sponsor’s disagreement
- Scientific and regulatory rationale
- A proposed resolution the sponsor is seeking
- Supporting documentation (clinical data)
As for who it’s sent to: That would be the next level up in the FDA’s chain of command, such as the Center for Disease Evaluation and Research (CDER) or the Center for Biologics Evaluation and Research (CBER).
Do we know what was included in Outlook’s FDRR?
The company’s submission consisted of a comprehensive presentation that detailed existing clinical, functional, and pharmacodynamic data as well as safety findings.
Outlook believes this data will “collectively support the efficacy and safety” of LYTENAVA for wet AMD treatment.
So what happens once submitted?
Providing the FDRR’s contents are deemed appropriate, the FDA will acknowledge receipt (as it just did in Outlook’s situation).
From there, an independent review will be conducted of the original FDA decision as well as the sponsor’s arguments and clinical data.
And the timeframe for this?
It can vary, ranging anywhere from 30 calendar days (once an FDRR is accepted) to beyond.
This may change depending on the complexity of the issue or if additional meetings are needed.
… and in Outlook’s case?
Not only has the FDA accepted this FDRR, but it has also “granted a meeting with the deciding official to be conducted in April 2026.”
No specific date was provided.
So we can expect a decision any day now, right?
Potentially.
And speaking of potential: If LYTENAVA is eventually approved by the FDA, it stands to become the first on-label bevacizumab product specifically formulated for intravitreal (IVT) retinal use in the U.S.