Top-line results from the Phase III INVIGORATE trial show Aldeyra Therapeutics’, reproxalap, significantly reduced ocular itching in patients with allergic conjunctivitis.
Reproxalap showing positive results in allergy-related eye problems.
Top-line results from the Phase III INVIGORATE trial show Aldeyra Therapeutics’ investigational novel small-molecule immune-modulating covalent inhibitor of RASP (reactive aldehyde species), reproxalap, significantly reduced ocular itching in patients with allergic conjunctivitis.
The randomized, double-blinded, two-way crossover study included 95 patients with allergic conjunctivitis. Patients were randomized to either 0.25% reproxalap ophthalmic solution or a vehicle control.
The primary efficacy endpoint included the change in participant-reported ocular itching score, based on a 0- to 4-point scale, from baseline to 11 time points ranging from 110 to 210 minutes following entry into the allergen chamber. Additionally, change in ocular redness over an approximate 3.5-hour period was also assessed by a 0- to 4-point scale, comprised of the secondary endpoint.
Patients who received reproxalap reported a significantly more significant reduction in the ocular itching score than patients treated with vehicle control over all 11 prespecified primary endpoints (p<0.0001). Additionally, patients treated with the investigational therapy had statistically significant reductions for the key secondary endpoint relative to the vehicle group (p<0.0001).
The investigators also observed substantial changes from baseline in patient-reported ocular tearing score over the allergen chamber duration in the reproxalap versus the placebo group (p<0.0001). The investigational treatment also led to a significantly more significant change from baseline in the total ocular severity score, an 11-point composite of the itching, redness, and tearing (p<0.0001).
“The statistically significant superiority of reproxalap over vehicle across all allergic conjunctivitis symptoms and signs assessed in INVIGORATE is remarkable, and suggests utility in one of the world’s most common ocular surface diseases,” according to a statement made by Aldeyra’s President and chief executive officer, Todd C. Brady, M.D., Ph.D. “We believe the consistent activity observed across chamber models in allergic conjunctivitis and dry eye disease bodes well for the commercial positioning of reproxalap as potentially the only broadly applicable topical anterior segment immune-modulating drug that may be used for chronic treatment, if approved for marketing.”
“Exacerbated by the rise in global temperatures, seasonal pollen counts are exploding, leading to escalations in the prevalence of allergic conjunctivitis and dry eye disease that are growing unchecked,” added Milton Hom, OD, of Canyon City Eyecare in Azusa, CA. “Even with the availability of treatments over the counter, many patients are using more than one prescription to manage ocular symptoms and redness. Based on my review of the INVIGORATE data, reproxalap, as one of the first new therapeutic mechanisms of action in years, would be a meaningful complement to the current treatment paradigm for moderate-to-severe allergic conjunctivitis patients.”
Previously reported findings from the Phase III ALLEVIATE trial also showed that treatment with 0.25% reproxalap leads to significant reductions in patient-reported ocular itching over just one hour compared with vehicle. Additionally, findings from the run-in cohort from the Phase III TRANQUILITY study reported in January showed that the therapy provided significant reductions in patient-reported ocular dryness scores and researcher-assessed ocular redness in the dry eye chamber in patients with dry eye disease.
In the most recent INVIGORATE trial, the investigators observed no safety or tolerability issues or adverse events aside from mild and temporary installation site discomfort typically found with other prescribed topical ophthalmic drugs for inflammation.
So far, a reproxalap solution has been given to over 1,200 patients in 14 trials. Aldeyra said in a statement that based on the findings from the INVIGORATE study, it will make plans to meet with the U.S. Food and Drug Administration sometime after the second quarter of this year to discuss the study results and the path forward for the submission of a New Drug Application for the therapy.
