Aldeyra Therapeutics’ investigational RASP modulator ADX-629 performed well in a Phase 2 clinical trial of patients with atopic dermatitis (AD), according to topline results.
Aldeyra expects to initiate a multicenter, randomized, placebo-controlled Phase 1/2 clinical trial of ADX‑246 in healthy volunteers and patients with AD in the first half of 2024. Topline results from the trial are expected in the second half of 2024.
The open-label, single-center Phase 2 clinical trial of ADX-629 included eight mild-to-moderate AD patients.
Over three months of treatment, patients received 250mg ADX-629, administered orally twice daily. The primary endpoint of the clinical trial was safety and tolerability. Secondary endpoints included Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numerical Rating Scale, time to flare, Hamilton Depression Rating Scale (HAM-D), and Beck Anxiety Inventory (BAI).
Relative to baseline, over three months of treatment, improvement was observed in all patients. Statistical significance was achieved for improvement in EASI. EASI thresholds for 50% improvement (EASI‑50), 75% improvement (EASI-75), and 90% improvement (EASI-90) were met in four patients (50%), three patients (38%), and one patient (13%), respectively. Statistical significance was achieved for improvement in affected body surface area); one patient (13%) achieved complete clearance of affected body surface area. Statistical significance was achieved for improvement in IGA. The IGA threshold score of 0 (clear) or 1 (almost clear) was met in one (13%) patient. Statistical significance was achieved for improvement in patient-reported itching; the clinically relevant threshold of improvement by 4 or more points was met in three patients (38%), and two patients (25%) reported elimination of itching. Statistical significance was achieved for improvement in patient-reported eczema severity; the clinically relevant threshold of improvement by 4 or more points was met in six patients (75%). Statistical significance was achieved for improvement in depression and numerical improvement was observed for improvement in anxiety, the study showed.
All enrolled patients completed the trial per protocol. No patients experienced flare requiring rescue therapy. Only two adverse events deemed to be at least possibly related to ADX-629 were reported, and both events were mild. There were no observed serious adverse events or discontinuations due to adverse events.
“The demand for safe, tolerable, and orally administered atopic dermatitis therapies, particularly for mild to moderate patients, is substantial,” says study author Matthew Zirwas, MD, founder of the Bexley Dermatology Research clinic in Bexley, Ohio, in a news release. “The data announced today offer a glimpse into what may be possible for many patients who today are not adequately treated.”
“The results from the clinical trial of ADX‑629 in atopic dermatitis are consistent with activity demonstrated in previously disclosed clinical trials of ADX‑629, including Phase 2 clinical trials in psoriasis, asthma, and chronic cough, adding to a growing body of evidence that we believe is supportive of the activity of RASP modulators in systemic diseases associated with inflammation,” adds Todd C. Brady, MD, PhD, President and Chief Executive Officer of Aldeyra. “Based on the signal-finding activity of ADX‑629, we enthusiastically plan to advance our next-generation investigational RASP modulator ADX‑246 to Phase 1/2 clinical testing in healthy volunteers and patients with atopic dermatitis.”
