Following the FDA's rejection of a third new drug application (NDA) for Aldeyra Therapeutics’ dry eye disease (DED) drop, the company intends to formally appeal the decision.
How: by submitting a formal dispute resolution request (FDRR).
The federal agency sent the company its third complete response letter (CRL) in a rejection of this latest attempt to secure regulatory approval.
Lots to debrief on here … first up: this drop.
You’re probably familiar with reproxalap, as the small-molecule modulator of reactive aldehyde species (RASP) has undergone quite the multi-year clinical journey up to this point.
If not, however, the following offers a quick rundown:
- Curious as to what exactly a RASP is? We explain here.
- Check out how Aldeyra’s RASP Modulator Platform impacts reproxalap's clinical effect.
- This debrief dives into how the drop works (and targets DED).
And you mentioned it’s already had three NDA submissions?
We did—and it has (we’ve covered them all, in fact).
See here for a full recap of these, with the first submitted in 2023.
What was the most recent update?
As we reported in March, the FDA issued yet another complete response letter (CRL) to Aldeyra regarding its latest attempt to secure regulatory approval.
The gist of that decision: Aldeyra said the FDA's third CRL found that the "totality of evidence from the completed clinical trials does not support the effectiveness of the product."
- See the full reasoning.
- Also check out that referenced clinical data.
Now to this FDRR.
First, a quick refresh: A formal dispute resolution request (FDRR) is a written appeal that a sponsor (Aldeyra, in this case) files when it disagrees with an FDA decision and wants it formally reviewed.
- The timing: This usually comes after a Type A meeting, when the issue (such as a rejected NDA) is still unresolved.
- The request goes to the next level up in the FDA's chain of command above the review division. Check out what’s typically included.
Speaking of timing … when does Aldeyra plan to submit its appeal?
Some time before the end of the year (Q4 2026), according to the company.
That goes for both FDRR submission as well as an expected meeting with the federal agency’s Office of New Drugs (OND)—the agency that will review Aldeyra’s FDRR.
Tell me more about this decision.
It followed two recent Type A and Type D meetings Aldeyra had with the FDA’s Division of Ophthalmology and the Office of Specialty Medicine
And once the FDRR is submitted, when would the FDA have an answer?
That’ll depend on “a number of factors,” including whether the deciding official requests additional information or determines “there’s a need to discuss the FDRR with internal or external experts or convene an advisory panel.”
At present, the exact “occurrence and timing” have not been established.
Did the company comment on the plan?
President and CEO Todd C. Brady, MD, PhD, noted that Aldeyra remains "steadfast" in its commitment to work with the FDA toward a reproxalap regulatory approval.
- “Based on the activity of reproxalap across a number of clinical trial designs, and against a backdrop of FDA dry eye disease product approvals that have applied considerable discretion, we are optimistic in the outcome of the FDRR,” he stated.
And of course, let’s also keep in mind that AbbVie, Inc. has an exclusive option to collaborate with Aldeyra on a U.S. commercialization of reproxalap.