Dry eye disease (DED) is a complex, chronic condition characterized by ocular discomfort, visual disturbance, tear film instability, increased tear osmolarity, conjunctival redness, and inflammation of the ocular surface that in severe cases can lead to loss of vision.
Dry eye disease (DED), which is usually incited by inflammation that requires long-term treatment to manage effectively, imposes a significant economic and humanistic burden, and patients with DED experience higher rates of depression and anxiety, increased lost work productivity, and decreased quality of life (QoL).
Treatment options for DED consist of artificial tears, antiinflammatory agents, antibiotics, and immunosuppressants. Aside from topical corticosteroids, which lead to ocular toxicity and must be restricted to short-term use, cyclosporine ophthalmic emulsion 0.05% and lifitegrast ophthalmic solution 5% are the only two anti-inflammatory ophthalmic drugs approved by the US Food and Drug Administration for the treatment of DED, and lifitegrast is the only drug approved for the treatment of the signs and symptoms of DED.
The most common side effects associated with lifitegrast are ocular irritation, blurred vision, and dysgeusia, and the most common side effect of cyclosporine is ocular irritation, all of which can occur after the initial instillation site discomfort that is characteristic of most prescription eye drops. Both the comfort associated with treatment instillation and the overall treatment tolerability strongly impact patient preferences and, by extension, the effectiveness of prescribed treatments. A clear unmet need exists in the population of patients with DED for novel therapeutics with improved eye drop experience profiles.
Reproxalap is a novel reactive aldehyde species inhibitor that covalently binds free aldehyde targets and has been shown in Phase 2a19 and Phase 2b20 clinical trials to be well tolerated and effective in mitigating the symptoms of DED. Reproxalap has also been shown to be well tolerated and effective in a Phase 3 clinical trial in allergic conjunctivitis and noninferior to topical corticosteroid use in a Phase 2 trial in patients with noninfectious anterior uveitis.
The objective of this head-to-head crossover clinical trial conducted by McMullin et al published in Clinical Ophthalmology was to compare the post-acute eye drop experience of two formulations of topical ocular reproxalap versus lifitegrast in subjects with DED after initial instillation site discomfort, which is characteristic of most prescription eye drops.
Two formulations of topical ocular reproxalap 0.25% were evaluated versus lifitegrast ophthalmic solution 5% in patients with DED in a single-center, double-masked, active-comparator, single-dose crossover clinical trial. Nineteen patients had test article topically administered to both eyes. Treatments were administered 2 to 4 days apart. Comfort assessments, including ocular discomfort, blurry vision, and dysgeusia assessments; ocular descriptive assessments; quality of life assessments; and overall experience questions were completed after each treatment over one hour, beginning at 90 seconds.
Both reproxalap formulations scored better in ocular discomfort score (ODS), blurry vision, and dysgeusia assessments than lifitegrast at each timepoint and cumulatively over all time points after instillation. There were lower rates of negative responses for both reproxalap formulations compared to lifitegrast across ocular discomfort, blurry vision, and dysgeusia assessments, and the durations of negative responses were shorter with reproxalap than with lifitegrast. The reproxalap groups experienced fewer quality of life impacts. No significant safety findings were observed following reproxalap or lifitegrast administration.
The reproxalap eye drop experience over 1 hour after instillation was superior to that of lifitegrast. There were no statistically significant differences between reproxalap groups for ODS, blurry vision, or dysgeusia. The improved performance of reproxalap with regard to the most commonly reported side effects of lifitegrast (ie, ocular discomfort, blurry vision, and dysgeusia) may result in greater patient adherence and lower discontinuation rates.
Source: McMullin et al; Clinical Ophthalmology 2021:15
https://doi.org/10.2147/OPTH.S327691