Aldeyra Therapeutics (ALDX) Study Update summary

Study background and design

• Phase 3 randomized, double-masked, vehicle-controlled dry eye chamber trial of reproxalap included 132 patients equally randomized to reproxalap or vehicle arms, following FDA feedback and a prior complete response letter.

• The dry eye chamber provided a controlled, low-humidity environment to acutely assess changes in ocular discomfort over 100 minutes.

• A vehicle run-in was used to exclude patients who did not escalate in discomfort, ensuring only responsive patients were randomized.

• The primary endpoint was patient-reported ocular discomfort from 80 to 100 minutes after chamber entry, with no secondary or exploratory endpoints.

• Trial protocol and statistical plan were developed with FDA feedback and Special Protocol Assessment.

Key results and efficacy

• The primary endpoint was met with a statistically significant p-value of 0.004, showing lower ocular discomfort with reproxalap versus vehicle at all assessed time points.

• Reproxalap-treated patients experienced approximately 75% less change from baseline in discomfort compared to vehicle.

• Rapid and sustained symptom improvement and acute reduction of ocular redness were observed, with rapid onset of symptom relief within minutes.

• No patients discontinued due to adverse events; reproxalap was well-tolerated, with mild, brief instillation site irritation as the most common adverse event.

• Over 2,500 patients have been studied with no major safety concerns and consistent safety profile.

Regulatory and commercial implications

• The trial fulfills the FDA's requirement for one additional symptom trial for NDA resubmission, anticipated in 2024.

• NDA review is expected to take six months; ongoing trials will not be completed before resubmission to avoid delays.

• An option agreement with AbbVie could lead to up to $400 million in milestone payments and profit sharing if exercised, with AbbVie holding U.S. co-exclusive and ex-U.S. exclusive rights.

• The unique rapid activity of reproxalap could differentiate it from current therapies, potentially allowing for both acute and chronic symptom relief labeling.

• Discussions with the FDA have confirmed that discomfort, dryness, and similar symptoms are considered substantially equivalent for endpoint purposes.