At a Glance
- Company: Aldeyra Therapeutics (NASDAQ: ALDX)
- Location: Lexington, Massachusetts
- Rejection reason: Efficacy not demonstrated in adequate studies
- Focus area: Dry eye disease (DED) treatment
- Next steps: FDA meeting; data from ongoing trials
What happened?
The US FDA issued a third complete response letter (CRL) to Aldeyra Therapeutics on 17 March 2026 for its NDA of reproxalap 0.25% ophthalmic solution in dry eye disease, stating the application “failed to demonstrate efficacy in adequate and well-controlled studies” for treating signs and symptoms. This follows prior CRLs in November 2023 and April 2025, both citing similar efficacy shortfalls despite new data submissions.
Why does it matter?
Reproxalap targets reactive aldehyde species (RASP) to reduce inflammation in immune-mediated eye diseases; repeated rejections raise doubts about its approvability in the competitive DED market (e.g., Xiidra, Restasis). Shares likely plunged, underscoring risks of iterative resubmissions without new pivotal trials.
Who’s behind it?
Aldeyra develops RASP modulators; reproxalap has AbbVie partnership for US rights. Despite no safety or manufacturing issues flagged in any CRL, FDA consistently questions clinical evidence from Phase 3 trials like dry eye chamber and field studies.
How was it achieved?
Third CRL came post-March 16 PDUFA extension for additional data review; FDA cited methodological concerns (e.g., baseline imbalances) affecting result interpretation. Aldeyra’s SPA-approved chamber trial showed symptom relief, but FDA deemed evidence insufficient per draft DED guidance requiring two sign and two symptom trials.
What’s next?
Aldeyra plans a Type A FDA meeting within 30 days to discuss CRL and ongoing field/chamber trials (topline Q2 2026). Potential fourth resubmission if data supports, though new trials may be needed; AbbVie option remains active.
What are people saying?
Aldeyra: “Future of reproxalap for dry eye in the US unclear.” FDA: “Failed to demonstrate efficacy… additional study needed.”