Aldeyra Therapeutics Announces Positive Topline Data from Phase 2 Dry Eye Chamber Clinical Trial of Reproxalap for Dry Eye Disease
Aldeyra Therapeutics announced positive topline data from a phase 2 clinical trial comparing ocular discomfort and itching symptom scores of reproxalap ophthalmic solution 0.25%, an investigational new drug, versus Xiidra (lifitegrast ophthalmic solution 5%) in patients with dry eye disease. Patient-reported ocular discomfort (P=0.002) and itching (P=0.01) were statistically lower with reproxalap than with Xiidra.
“The statistically significant symptom improvement of reproxalap over Xiidra observed in this trial reinforces the data from an earlier clinical trial demonstrating tolerability advantages of reproxalap over Xiidra in patients with dry eye disease,”1 Todd C. Brady, MD, PhD, President and Chief Executive Officer of Aldeyra, said in a company news release. “The combination of rapid activity and improved tolerability evidenced by reproxalap in clinical testing has the potential to address significant compliance issues with currently available therapy, the median discontinuation rates of which are approximately one month.”2
“The clinically relevant and statistically significant reduction in symptomatic activity suggest that reproxalap, if approved, has the potential to become a first-line therapy for the treatment of dry eye disease,” stated Peter Couroux, MD, Global Senior Medical Director for Cliantha Research and the principal investigator of the clinical trial. “As the first RASP modulator developed for ocular surface disease, reproxalap represents a new mechanism of action that may expand the treatment options available to dry eye disease patients.”
The double-masked, crossover, single-center, phase 2 clinical trial in 56 dry eye disease patients evaluated the activity of reproxalap compared to Xiidra for two endpoints: ocular discomfort symptom score and ocular itching symptom score. A single dose of test article was administered to both eyes approximately 5 minutes prior to a dry eye chamber exposure lasting 45 minutes, during which humidity was maintained at low levels in a setting of regulated air flow, temperature, and visual tasking. Symptoms were assessed approximately 15 minutes prior to chamber entry, and every 5 minutes beginning 5 minutes after chamber entry.
No safety signals were observed in the trial, and there were no treatment-related discontinuations or moderate or serious adverse events related to drug. The most common adverse event in both treatment arms was mild instillation site discomfort. Reproxalap has now been evaluated in more than 1,500 patients. The approved commercial dosing regimen of Xiidra and the intended commercial dosing regimen of reproxalap include repeated administration of drug.
Aldeyra plans to present data from the trial at an upcoming medical meeting.
About Reproxalap
Reproxalap, an investigational new drug, is a novel small-molecule modulator of RASP (reactive aldehyde species), which are elevated in ocular and systemic inflammatory disease. Reproxalap’s mechanism of action has been supported by the demonstration of statistically significant and clinically relevant activity in multiple physiologically distinct late-phase clinical indications. Reproxalap is currently in Phase 3 clinical development as a 0.25% ophthalmic solution for the treatment of dry eye disease and allergic conjunctivitis, two of the largest markets in ophthalmology.
References
1 McMullin D, Clark D, Cavanagh B, Karpecki P, Brady TC. A Post-Acute Ocular Tolerability Comparison of Topical Reproxalap 0.25% and Lifitegrast 5% in Patients with Dry Eye Disease. Clin Ophthalmol. 2021 Sep 22;15:3889-3900.
2 White DE, Zhao Y, Ogundele A, Fulcher N, Acs A, Moore-Schiltz L, Karpecki PM. Real-World Treatment Patterns Of Cyclosporine Ophthalmic Emulsion And Lifitegrast Ophthalmic Solution Among Patients With Dry Eye. Clin Ophthalmol. 2019 Nov 22;13:2285-2292.
3 Paulsen AJ, Cruickshanks KJ, Fischer ME, Huang GH, Klein BE, Klein R, Dalton DS. Dry eye in the beaver dam offspring study: prevalence, risk factors, and health-related quality of life. Am J Ophthalmol. 2014 Apr;157(4):799-806. doi: 10.1016/j.ajo.2013.12.023. Epub 2014 Jan 2. PMID: 24388838; PMCID: PMC3995164.
4 Choi W, Lian C, Ying L, Kim GE, You IC, Park SH, Yoon KC. Expression of Lipid Peroxidation Markers in the Tear Film and Ocular Surface of Patients with Non-Sjogren Syndrome: Potential Biomarkers for Dry Eye Disease. Curr Eye Res. 2016 Sep;41(9):1143-9. doi: 10.3109/02713683.2015.1098707. Epub 2016 Jan 5. PMID: 26731289.