Reproxalap Safe for Use in Patients With Dry Eye Disease

Reproxalap was found to be safe to take in patients diagnosed with dry eye disease (DED), as no serious treatment-emergent adverse events (TEAEs) were reported in patients taking the medication. These findings, published in Ophthalmology Therapy,¹ indicate that reproxalap is a safe option for treating DED.

DED is an eye condition that affects tear film due to either not producing enough tears or because the tears evaporate too quickly.² This can cause instability, inflammation, and ocular discomfort, including burning, itching, and a gritty feeling in the eye. DED requires treatment over months or years, and episodic flares of DED are common during times of low humidity, increased wind, or prolonged use of screens. Reproxalap is a reactive aldehyde species (RASP) inhibitor that can help to block the initiation of production and release of proinflammatory cytokines, which can alleviate symptoms of DED.¹ This study aimed to see if reproxalap 0.25% ophthalmic solution was a safe method of treating DED when compared with the vehicle. Best-corrected visual acuity (BCVA) was also evaluated.

The study was conducted from January 26, 2021, to October 11, 2022, across 14 sites in the US. Patients were enrolled if they were aged 18 years and older and had at least a 6-month history of DED. Patients also needed to either express an interest in eye drops or have a history of using ye drops. All patients needed a score of 2 or higher for at least 1 symptom on the Ora Calibra Ocular Discomfort and 4-Symptom Questionnaire (OD4SQ) and a Schirmer test score of 1 to 10 mm.

Approximately 40% of the participants were enrolled in a 6-week treatment cohort, and 60% were enrolled in a 12-month treatment cohort; patients were then split in a 2:1 ratio for bilateral treatment of reproxalap or vehicle. Patients administered the drops themselves 4 times per day for the first 4 weeks and twice per day for the remaining time in the clinical trial. Follow-up visits were at 4 and 6 weeks for both cohorts and months 3, 6, 9, and 12 for those taking the treatment for a year. Primary end points were the proportion of patients with serious TEAEs related to visual acuity decrease, an increase in intraocular pressure (IOP), retinal events, and corneal events.

There were 757 participants who were initially enrolled in the study, with 11.1% in the reproxalap and 2.8% in the vehicle discontinuing due to AEs. Site irritation was the primary reason for the reproxalap 6-week (8.0%) and 12-month (9.0%) groups to discontinue use. The mean age was 56.0 years in the 6-week group and 55.6 years for the 12-month group.

No serious TEAEs were reported in the overall population. The TEAEs that were reported were primarily ocular and mild. Maximum severity was mild in 94% of the participants in the 6-week group and 84% in the 12-month group. Instillation site irritation was the most common TEAE in patients treated with reproxalap. The probability of irritation increased by 3% for each 1-year increase in the age of the patient; irritation was also twice as likely in women. The odds of irritation decreased by 10% for each point higher in the baseline QD4SQ.

The mean improvement in BCVA was better with reproxalap compared with vehicle in the 12-month safety populations, though both saw small improvements from their baseline BCVA measurement. Other safety assessments found no safety concerns.

There were some limitations to this study. The protocol was not powered for rare AEs. Logistic regression analyses were not statistically powered. The study included patients who were treated outside of a dry eye chamber, which is different than other trials with reproxalap and could affect tolerability profiles. Selection bias is possible due to the exclusion of patients who were not willing to discontinue their ocular therapies. Symptomatic comparisons between excluded patients and those that enrolled were not performed.

“The results of the clinical trial reported herein support the safety of long-term topical reproxalap therapy in patients with DED,” the authors concluded. “Reproxalap has potential to be a safe and effective first-in-class new therapy for DED that alleviates inflammation by inhibiting RASP.”

References

1. Radcliffe NM, Sheppard J, Simmons B, et al. Phase 3 randomized clinical trial evaluating the safety of reproxalap in patients with dry eye disease. Ophthalmol Ther. Published online April 11, 2026. doi:10.1007/s40123-026-01379-0
2. Dry eye. Cleveland Clinic. Updated June 20, 2025. Accessed April 13, 2026. https://my.clevelandclinic.org/health/diseases/24479-dry-eye