Reproxalap relieves itchy eyes in patients with allergic conjunctivitis

In patients with allergic conjunctivitis, treatment with the novel reactive aldehyde species (RASP) inhibitor reproxalap appears to produce a dramatic reduction in ocular itching, according to the results of the ALLEVIATE trial.

“ALLEVIATE represents the first phase III trial to assess post-acute allergy over 1-hour following challenge, which lasts longer than histaminic allergy and is more clinically relevant than reported conjunctival allergen challenge trials that typically assess itching response only through 7 minutes after allergen challenge,” the investigators said. [Clin Ophthalmol 2015;9:1703-1713]

“Across the continuum of area under the curve responses, both [0.25% and 0.5%] concentrations were superior to vehicle … indicating that, irrespective of the particular response threshold considered to be clinically relevant, reproxalap treatment led to a greater number of responders than did vehicle treatment,” they added.

In the trial, 318 patients (mean age 45.7 years, 61.9 percent female) were randomized to receive topical ocular reproxalap concentrations at either 0.25% (n=109) or 0.5% (n=100) or vehicle (n=109). Treatment was administered 10 minutes prior to conjunctival seasonal allergen challenge.

Both concentrations of reproxalap (0.25% and 0.5%) achieved the primary endpoint of improvement in area under the post-acute ocular itching score curve from 10 to 60 minutes after the challenge (p<0.0001 and p=0.003, respectively), as well as the key secondary endpoint of patients achieving ≥2 points improvement in their peak ocular itching score from baseline (p=0.0005 and p=0.02, respectively).

Compared with the vehicle, active treatment was associated with markedly lower mean ocular itching scores at every postchallenge time point (10, 20, 30, 40, 50, and 60 minutes) except at the 5-minute mark. The improvement was numerically greater for the lower concentration, with most patients achieving a score of 0, which indicated the absence of itch. In contrast, patients in the vehicle group commonly had a score of 2. [Am J Ophthalmol 2021;doi:10.1016/j.ajo.2021.04.023]

Time to complete resolution of ocular itching was shorter for both reproxalap concentrations than for the vehicle (p<0.0001 and p=0.001, respectively).

No safety or tolerability concerns emerged for reproxalap. Mild transient instillation site irritation was the most common adverse event.

All patients had a history of allergic conjunctivitis, a positive skin test to 126 seasonal allergens, and conjunctival allergen challenge itching and redness scores of ≥2.5 and ≥2 (measured using the Ora Calibra Ocular Itching and Hyperemia Scales, with scores ranging from 0 [none] to 4 [severe]), respectively, at baseline. None of them reported use of antihistamine, corticosteroid, and immunotherapeutic agents in the immediate period prior to screening.

“Consistent with US Food and Drug Administration and European Medicines Agency guidelines, the clinical relevance assessments reported herein include prespecified responder definition analyses supported by distribution-based methods. The results from ALLEVIATE, for example, suggest that, after exposure to allergen and relative to using an inactive topical solution, treatment with reproxalap 0.25% leads to faster resolution of symptoms and increases the chance of clinical response by at least twofold,” the investigators explained.

As a topically administered RASP inhibitor, reproxalap has demonstrated clinical activity in noninfectious anterior uveitis, dry eye disease, and allergic conjunctivitis. [J Ocul Pharmacol Ther 2020;36:732-739; Am J Ophthalmol 2021;226:22-31; Invest Ophthalmol Vis Sci 2018;59:5571-5571]

“Given the activity of reproxalap in the conjunctival challenge model, further testing of [the drug] in other allergen challenge models, such as an allergen chamber in which prolonged exposure can be achieved, is warranted,” the investigators said.