reproxalap ophthalmic (ADX-102 ophthalmic) / Aldeyra, Ligand, AbbVie - LARVOL DELTA

Ophthalmic Treatments and Evolving Management of Sjögren's Disease: An Overview. (PubMed, J Clin Med) - "Additionally, emerging therapeutics are shifting care from palliative lubrication to targeted secretomotor and biological reactivation, including cold thermosensory TRPM8 agonists (acoltremon 0.003%), water-free formulations (0.1% cyclosporine, perfluorohexyloctane), reactive aldehyde species (RASP) modulators (reproxalap), syndecan-1 receptor agonists (Lacripep), systemic B-cell depleting biotherapy (ianalumab), trigeminal neurostimulation, and combined intense pulsed light with meibomian gland expression (IPL + MGX). Ophthalmic SjD management has evolved from palliative lubrication toward a stepwise, mechanism-directed paradigm integrating novel diagnostics, secretomotor stimulation, mechanical protection, and biologic disease modification; dedicated SjD-specific trials remain essential to validate these emerging interventions."

Journal • Review • Conjunctivitis • Dry Eye Disease • Inflammation • Keratitis • Ocular Infections • Ocular Inflammation • Ophthalmology • Sjogren's Syndrome • MMP9 • SDC1 • TRPM8

Reproxalap - A Novel Treatment Option for Allergic Conjunctivitis - A Comprehensive Narrative Review. (PubMed, Health Sci Rep) - "Reproxalap represents a first-in-class RASP inhibitor with promising efficacy and safety for the treatment of allergic conjunctivitis. Its unique mechanism of action and encouraging clinical trial outcomes support its potential as a valuable therapeutic alternative that may improve patient outcomes and could also be applicable in other inflammatory ocular conditions."

Journal • Conjunctivitis • Immunology • Inflammation • Ocular Infections • Ocular Inflammation • Ophthalmology

Phase 3 Randomized Clinical Trial Evaluating the Safety of Reproxalap in Patients With Dry Eye Disease. (PubMed, Ophthalmol Ther) - P3 | "The results support the safety of long-term topical reproxalap therapy in patients with DED."

Clinical • Journal • P3 data • Dry Eye Disease • Inflammation • Ocular Inflammation • Ophthalmology

Aldeyra Therapeutics Receives Complete Response Letter from the U.S. Food and Drug Administration for the Reproxalap New Drug Application for the Treatment of Signs and Symptoms of Dry Eye Disease (Aldeyra Therapeutics Press Release) - "The CRL stated that there is 'a lack of substantial evidence consisting of adequate and well-controlled investigations … that the drug product will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in its proposed labeling' and that 'the application has failed to demonstrate efficacy in adequate and well controlled studies in the treatment of signs and symptoms of dry eye disease.' The letter also stated that the 'inconsistency of study results raises serious concerns about the reliability and meaningfulness of the positive findings'...Per Prescription Drug User Fee Act (PDUFA) goals, the target Type A meeting date is within 30 days of receipt of the meeting request."

CRL • Dry Eye Disease

Aldeyra Therapeutics Announces PDUFA Extension of the New Drug Application of Reproxalap for the Treatment of Dry Eye Disease (Businesswire) - "The extended PDUFA target action date is March 16, 2026....At the December 12 meeting, the FDA made no other requests and did not identify any other specific issues with the NDA review. The CSR, which had been previously submitted to the Investigational New Drug (IND) file for reproxalap, was submitted to the NDA the same day of the meeting and was considered a major amendment to the NDA by the FDA."

PDUFA • Dry Eye Disease

Reproxalap Improves Ocular Redness, Tear Production, and Symptoms in a Pivotal Dry Eye Disease Chamber Trial. (PubMed, Ophthalmol Sci) - "Within minutes of administration to dry eye disease patients, reproxalap increased tear production, and decreased ocular redness and improved symptoms in a dry eye chamber. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article."

Journal • Dry Eye Disease • Ophthalmology

Aldeyra Therapeutics Announces FDA Acceptance for Review of Reproxalap New Drug Application for the Treatment of Dry Eye Disease (Aldeyra Therapeutics Press Release) - "Aldeyra Therapeutics, Inc...announced that the U.S. Food and Drug Administration (FDA) has accepted for review the resubmitted New Drug Application (NDA) for topical ocular reproxalap, a first-in-class investigational new drug candidate, for the treatment of the signs and symptoms of dry eye disease. The FDA assigned a Prescription Drug User Fee Act (PDUFA) target action date of December 16, 2025."

FDA filing • PDUFA • Dry Eye Disease

Reproxalap ophthalmic: FDA action date for dry eye disease in Dec 2025 (Aldeyra Therapeutics) - Corporate Overview

PDUFA • Dry Eye Disease • Ophthalmology

Aldeyra Therapeutics Resubmits Reproxalap New Drug Application for the Treatment of Dry Eye Disease (Aldeyra Therapeutics Press Release) - "Aldeyra Therapeutics, Inc...announced the resubmission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for topical ocular reproxalap, an investigational new drug candidate, for the treatment of signs and symptoms of dry eye disease. Per FDA agreement, the only new clinical data included in the resubmitted NDA were from the recently completed dry eye chamber trial, which achieved the primary endpoint."

FDA filing • Dry Eye Disease

A Trial to Assess the Safety and Efficacy of Subjects With Dry Eye Disease (clinicaltrials.gov) - P3 | N=116 | Completed | Sponsor: Aldeyra Therapeutics, Inc. | Recruiting ➔ Completed

Trial completion • Dry Eye Disease • Ophthalmology

A Clinical Trial to Assess the Safety and Efficacy of Subjects With Dry Eye Disease (clinicaltrials.gov) - P3 | N=421 | Completed | Sponsor: Aldeyra Therapeutics, Inc. | Recruiting ➔ Completed

Trial completion • Dry Eye Disease • Ophthalmology

Aldeyra Therapeutics Achieves Primary Endpoint in Phase 3 Dry Eye Disease Chamber Trial of Reproxalap and Plans NDA Resubmission (Businesswire) - P3 | N=757 | NCT04735393 | Sponsor: Aldeyra Therapeutics, Inc. | "Aldeyra Therapeutics...announced the achievement of the primary endpoint in a Phase 3 randomized, double-masked, vehicle-controlled dry eye chamber trial of 0.25% reproxalap ophthalmic solution, an investigational new drug candidate, for the treatment of dry eye disease. For the prespecified primary endpoint of ocular discomfort, a symptom of dry eye disease, reproxalap (n=58) was statistically significantly superior to vehicle (n=58) on ocular discomfort symptom score (0‑100) from 80 to 100 minutes after chamber entry (LS mean difference [95% confidence interval] ‑6.5 [‑10.5, ‑2.5], P=0.002). Aldeyra believes that the dry eye chamber trial results...potentially address the U.S. Food and Drug Administration (FDA) feedback in a Complete Response Letter received in April 2025....Pending a Type A meeting with the FDA, NDA resubmission is anticipated mid‑2025, and the review period is expected to be six months."

FDA filing • P3 data • Dry Eye Disease

Aldeyra Therapeutics, Inc. (ALDX) Faces Scrutiny After Stock Drops 70% On FDA’s Reproxalap Complete Response Letter – Hagens Berman (GlobeNewswire) - "On April 3, 2025 investors in Aldeyra Therapeutics...saw the price of their shares crash over 70% after the company announced that it received a Complete Response Letter ('CRL') from the FDA for the resubmission of the New Drug Application ('NDA') of reproxalap, an investigational drug candidate, for the treatment of dry eye disease."

CRL • Stock price • Dry Eye Disease

Aldeyra Therapeutics Receives Complete Response Letter from the U.S. Food and Drug Administration for the Reproxalap New Drug Application for the Treatment of Signs and Symptoms of Dry Eye Disease (Aldeyra Therapeutics Press Release) - "Aldeyra Therapeutics...announced receipt of a Complete Response Letter from the U.S. Food and Drug Administration (FDA) for the resubmission of the New Drug Application (NDA) of reproxalap...Although no manufacturing or safety issues with reproxalap were identified, the FDA stated in the letter that the NDA 'failed to demonstrate efficacy in adequate and well controlled studies in treating ocular symptoms associated with dry eyes' and that 'at least one additional adequate and well controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye' should be conducted....In the second quarter of 2025, Aldeyra expects to announce top-line results from the ongoing dry eye disease field trial and the ongoing chamber clinical trial. Subject to positive results and discussions with the FDA, Aldeyra intends to resubmit the NDA mid-year 2025. The review period for the potential NDA resubmission is expected to be six months."

CRL • FDA filing • P3 data: top line • Dry Eye Disease

A Multi-Center, Randomized, Double Masked, Parallel-Group, Vehicle-Controlled, Clinical Study to Assess the Safety and Efficacy of Reproxalap Ophthalmic Solution in Subjects With Dry Eye Disease (clinicaltrials.gov) - P2 | N=300 | Completed | Sponsor: Aldeyra Therapeutics, Inc. | Phase classification: P2b ➔ P2

Phase classification • Dry Eye Disease • Ophthalmology

A Randomized, Double Masked, Clinical Study of Subjects With Dry Eye Syndrome (clinicaltrials.gov) - P2 | N=51 | Completed | Sponsor: Aldeyra Therapeutics, Inc. | Phase classification: P2a ➔ P2

Phase classification • Dry Eye Disease • Ophthalmology

Aldeyra Therapeutics Announces FDA Acceptance for Review of Reproxalap New Drug Application for the Treatment of Dry Eye Disease, Expands AbbVie Option Agreement (Businesswire) - "Aldeyra Therapeutics, Inc...announced that the U.S. Food and Drug Administration (FDA) has accepted for review the resubmitted New Drug Application (NDA) for topical ocular reproxalap, a first-in-class investigational new drug candidate, for the treatment of the signs and symptoms of dry eye disease. The FDA assigned a Prescription Drug User Fee Act (PDUFA) date of April 2, 2025. In conjunction with the acceptance of the NDA for review, Aldeyra announced the expansion of its exclusive option agreement with AbbVie Inc. (AbbVie)."

FDA filing • PDUFA • Dry Eye Disease • Ophthalmology

Quintessence of currently approved and upcoming treatments for dry eye disease. (PubMed, Graefes Arch Clin Exp Ophthalmol) - "Currently, the US Food and Drug Administration (FDA)-approved medical treatments for treatment of DED include cyclosporine formulations (RESTASIS® [cyclosporine 0.05% ophthalmic emulsion], VEVYE® [cyclosporine 0.1% ophthalmic solution], and CEQUA™ [cyclosporine 0.09% ophthalmic solution]), XIIDRA® (lifitegrast), a leukocyte function-associated antigen-1 (LFA-1)/intracellular adhesion molecule-1(ICAM-1) inhibitor, EYSUVIS™ (loteprednol etabonate ophthalmic suspension 0.25%), a corticosteroid, and MIEBO™ (perfluorohexyloctane ophthalmic solution), a semifluorinated alkane. TYRVAYA™ (varenicline solution nasal spray), a cholinergic agonist, is another formulation approved for the treatment of the signs and symptoms of DED...Cyclosporine formulations TJO-087 (cyclosporine A nanoemulsion 0.08%), SCAI-001 eye drops (cyclosporine 0.01%, 0.02%) are being evaluated against RESTASIS® and other approved treatments. The potential treatments being assessed include..."

Journal • Review • Conjunctivitis • Dry Eye Disease • Ocular Infections • Ocular Inflammation • Ophthalmology • Sjogren's Syndrome • ICAM1

Reproxalap ophthalmic : “The phase 3 dry eye chamber clinical trial achieved the primary endpoint of ocular discomfort”; Dry eye disease (Aldeyra Therapeutics) - Phase 3 Dry Eye Disease Clinical Trial of Reproxalap

P3 data: top line • Dry Eye Disease • Ophthalmology

A Trial to Assess the Safety and Efficacy of Subjects With Dry Eye Disease (clinicaltrials.gov) - P3 | N=110 | Recruiting | Sponsor: Aldeyra Therapeutics, Inc.

New P3 trial • Dry Eye Disease • Ophthalmology

A Clinical Trial to Assess the Efficacy and Safety of Subjects With Dry Eye Disease (clinicaltrials.gov) - P3 | N=132 | Completed | Sponsor: Aldeyra Therapeutics, Inc. | Recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ Jun 2024 | Trial primary completion date: Dec 2024 ➔ Jun 2024

Trial completion • Trial completion date • Trial primary completion date • Dry Eye Disease • Ophthalmology

Reproxalap ophthalmic: Top-line data from P3 trial (NCT04735393) for dry eye disease in H2 2024 (Aldeyra Therapeutics) - Research & Development Day 2024

P3 data: top line • Dry Eye Disease • Ophthalmology

Reproxalap ophthalmic: NDA resubmission in US for dry eye disease in H2 2024 (Aldeyra Therapeutics) - Research & Development Day 2024

FDA filing • Dry Eye Disease • Ophthalmology

A Phase 3 Clinical Trial to Assess the Efficacy and Safety of Subjects With Dry Eye Disease (clinicaltrials.gov) - P3 | N=400 | Recruiting | Sponsor: Aldeyra Therapeutics, Inc.

New P3 trial • Dry Eye Disease • Ophthalmology

A Phase 3 Clinical Trial to Assess the Efficacy and Safety of Subjects With Dry Eye Disease (clinicaltrials.gov) - P3 | N=110 | Recruiting | Sponsor: Aldeyra Therapeutics, Inc.

New P3 trial • Dry Eye Disease • Ophthalmology