Aldeyra Therapeutics announced positive topline results from Part 1 of the adaptive phase 3 RENEW trial of topical ocular reproxalap in patients with dry eye disease, according to a company news release.
“To our knowledge, reproxalap is the first topical dry eye disease drug to demonstrate statistically significant ocular dryness symptom improvement relative to vehicle as soon as one week after initiation of treatment, and thus has the potential to be first-line therapy,” Todd C. Brady, MD, PhD, President and Chief Executive Officer of Aldeyra, said in the news release. “The breadth of symptomatic activity highlighted by the induction-maintenance dosing regimen results in RENEW Part 1 demonstrate the potential of reproxalap in treating dry eye disease, one of the largest, yet least-served, markets in ophthalmology.”
The RENEW trial is an ongoing adaptive, two-part, multicenter, randomized, vehicle-controlled, double-masked, parallel-group phase 3 trial of 0.25% topical ocular reproxalap compared to vehicle in patients with moderate to severe dry eye disease. The primary objective of RENEW Part 1 was to confirm dosing regimen, endpoints, and sample size for RENEW Part 2. In Part 1 of RENEW, 422 patients were randomized equally to receive either 4-times-daily reproxalap or vehicle for 12 weeks (the constant dosing group) or 4-times-daily reproxalap or vehicle for 4 weeks, followed by twice-daily reproxalap or vehicle for 8 weeks (the induction-maintenance dosing group).
The primary objective of RENEW Part 1 was achieved. Observed activity versus vehicle of the induction-maintenance dosing regimen of topical ocular reproxalap was greater than that of the constant dosing group, and the induction-maintenance dosing regimen will be advanced to RENEW Part 2. The planned primary endpoints for RENEW Part 2 are ocular dryness score and fluorescein nasal region ocular staining score. RENEW Part 2 is expected to initiate in the first half of 2020 and enroll approximately 400 patients per arm at approximately 90% power to achieve statistical significance.
In the induction-maintenance dosing group, the RENEW co-primary endpoint of patient-reported visual analog scale (VAS) ocular dryness from Weeks 2 to 12 was achieved (P=0.0004), and activity was observed as early as 1 week after initiation of therapy (P=0.001) and was maintained until the end of the trial. In the induction-maintenance dosing group from Weeks 2 to 12, reproxalap was statistically superior to vehicle in VAS ocular endpoints for itching (P=0.03), foreign body sensation (P=0.004), discomfort (P=0.003), photophobia (P=0.004), and pain (P=0.03). In the induction-maintenance dosing group from Weeks 2 to 12, reproxalap was statistically superior to vehicle in Ocular Discomfort & 4-Symptom Questionnaire ocular endpoints for dryness (P=0.01), discomfort (P=0.03), burning (P=0.03), grittiness (P=0.003), and stinging (P=0.02). Although the improvement effect size of the co-primary endpoint of fluorescein nasal region ocular staining did not reach statistical significance, reproxalap was statistically superior to vehicle in reduction from baseline in the induction-maintenance dosing group from Weeks 1 to 4 of treatment (P=0.03), and statistical separation from vehicle was observed at Week 2 (P=0.04).
“The rapid amelioration of symptoms followed by symptomatic control in the induction-maintenance dosing regimen supports the potential of reproxalap to treat a wide range of dry eye disease states, from severe flares to persistent symptoms,” Dr. David Clark, Chief Medical Officer of Aldeyra, said in the news release. “In addition, consistent with our positive phase 3 results in allergic conjunctivitis, reproxalap is one of the first dry eye disease drugs to demonstrate activity in reducing ocular itching, a prominent symptom associated with dry eye disease exacerbation, which is especially common during allergy seasons.”
Consistent with clinical experience in over 1,100 patients, no adverse findings on safety assessments were observed, and reproxalap was well-tolerated. The most common reported adverse event in reproxalap-treated patients was transient and mild instillation site irritation. Less than 8% of reproxalap-treated patients discontinued the trial due to adverse events, and moderate ocular adverse events were reported in fewer than 1% of subjects.
“Today’s dry eye disease population is underserved, and novel therapies are in demand. Currently available therapies often require weeks or months to demonstrate activity, and many patients exhibit limited or no response, leading to between 50% to 80% of patients dropping off therapy between their second and third refill,” David McMullin, Chief Commercial Officer of Aldeyra, said in the news release. “The early-onset and broad pattern of symptom improvement in the induction-maintenance dosing regimen of reproxalap demonstrated in RENEW Part 1 represents an attractive profile in the dry eye disease market.”