Aldeyra Therapeutics, Inc. has resubmitted its new drug application (NDA) for 0.25% reproxalap ophthalmic solution, a potential treatment for dry eye disease (DED).
This submission follows previous FDA concerns over the company’s initial NDA submission of reproxalap in 2022—and new phase 3 data supporting its second try.
Let’s start with a refresh on reproxalap.
Important to know: The candidate is Aldeyra’s first-in-class, small-molecule modulator of a reactive aldehyde species (RASP).
- About RASP: This class of molecules can be elevated in ocular and systemic inflammatory disease as well as cause:
- Decrease in tear production
- Conjunctival hyperemia
- Change in lipid tear composition
- Increased ocular inflammation
- Learn about the company’s RASP Modulator Platform
How long does it take to work?
Previous study data on reproxalap for DED found that it demonstrated signs of activity ranging from within minutes of administration to up to 12 weeks.
Speaking of clinical data …
Reproxalap originally underwent clinical investigation in over 2,000 patients in five well-controlled studies.
The crux of those findings: Safety and efficacy results supported its impact on:
- Ocular dryness symptom score
- Ocular redness
- Schirmer test
- Schirmer test ≥10 mm responder analysis
Plus: The candidate is also undergoing clinical trials for allergic conjunctivitis (with topline phase 3 data released in June 2023.
And more recent data?
In August 2024, Aldeyra reported positive phase 3 results from a randomized, double-masked, vehicle-controlled dry eye chamber study.
The details: Reproxalap achieved the study’s sole primary endpoint—ocular discomfort from 80 to 100 minutes in the dry eye chamber—and was found to be well tolerated.
- As far as adverse events (AEs): The most commonly reported was mild and transient instillation site discomfort.
- Plus: No treatment-related discontinuations occurred among participants.
And what was significant about these findings?
The company noted that reproxalap became (to its knowledge) “the first investigational drug with pivotal data supportive of acute and chronic activity in reducing (DED) symptoms.”
Nice! Circle back to those prior FDA concerns you mentioned earlier …
It’s easier if we just give you a timeline:
- February 2023: The FDA accepted Aldeyra’s original NDA for reproxalap
- A Prescription Fee Drug User Act (PDUFA) deadline was set for Nov. 23, 2023.
- October 2023: The agency identified substantive review issues following a late-cycle review meeting with Aldeyra on the drug’s study data (see here for details) from their clinical trials
- FDA requested more data on its chemistry, manufacturing, and controls (CMC) processes.
- November 2023: The company received a company response letter from the FDA with concerns over the candidate’s adequacy of clinical evidence for its indication
- Per the agency: Reproxalap’s NDA failed to demonstrate efficacy for treating ocular symptoms associated with dry eye
- Also: At least one additional adequate and well-controlled study is needed to demonstrate a positive effect on the treatment of ocular symptoms of dry eye
- Then: Aldeyra submitted a special protocol assessment (SPA) for a dry eye chamber crossover trial on reproxalap (ie: that phase 3 study data we mentioned earlier)
That’s … a lot. So what’s the company focusing on now?
Aldeyra reported that, per FDA PDUFA guidelines on NDA submissions, the agency must acknowledge its acceptance of the NDA within 30 days—and complete its submission within 6 months.