Aldeyra Therapeutics, Inc., a biotechnology company dedicated to discovering and developing innovative therapies designed to treat immune-mediated diseases, today announced overall positive results from Phase 2 clinical trial of ADX Intravitreal -2191 (methotrexate injection, USP), an investigational drug candidate, in patients with retinitis pigmentosa. Compared to baseline, the clinical trial demonstrated statistically significant improvement in retinal function across a number of different physiological and psychophysiological assessments.
Based on preclinical data showing that methotrexate can facilitate clearance of mutant rhodopsin1, a protein essential for visual cycle function, an open-label, phase 2 ADX-2191 clinical trial, Single-center monotherapy was performed in eight patients with retinitis pigmentosa with mutant rhodopsin folds. During three months of treatment with ADX-2191, four patients received monthly injections and four patients received biweekly injections. The primary endpoint of a clinical trial was safety. Secondary endpoints included change from baseline in visual acuity; retinal function, as assessed by macular and dark-adapted EEG and EEG methods; and retinal morphology, as assessed by optical coherence tomography. Visual acuity, circumference, and morphometric assessments were performed monthly for four months from initiation of treatment. EEG was performed at baseline and 90 days after initiation of treatment.All enrolled patients completed the trial according to the protocol. Compared to baseline, in all patients, statistical significance was achieved for improvement in best corrected visual acuity (P<0.0001), low-light acuity (P=0.0001), retinal electrical response time to light (P=0.02), macular light sensitivity (P<0.0001) and light-adapted sensitivity to peripheral darkness (P<0.0001). ADX-2191 was well tolerated and no safety issues were identified. No treatment-related adverse events related to retinal morphology were observed. No serious adverse events were reported and no patient discontinued treatment due to adverse events.“The improvement in retinal function relative to baseline observed in this retinitis pigmentosa clinical trial of ADX-2191 may offer hope to patients that today have no therapeutic options,”
“Based on compelling proof-of-concept clinical activity that is consistent with a well-defined mechanism of action supported by preclinical evidence, we are excited to meet with regulatory authorities to discuss initiation of a potentially pivotal Phase 2/3 clinical trial, as we enthusiastically advance ADX-2191 to the next stage of development.”
Todd C. Brady, M.D., Ph.D., President and CEO of Aldeyra.
ADX-2191 is a new vitreous methotrexate formulation in clinical development for proliferative retinopathy and retinitis pigmentosa, both rare and vision-threatening retinopathy without approved therapy. The prevalence of retinitis pigmentosa is more than one million people worldwide, and the gene mutations that lead to rhodopsin misfolding account for about one-third of cases. ADX-2191 has received Orphan Drug Designation from the US Food and Drug Administration for the treatment of vitreous proliferative disease and retinitis pigmentosa.“Retinitis pigmentosa is a relentlessly progressive disease that inevitably leads to loss of vision,”
“The promising results presented today are supportive of a potential novel approach for the treatment of retinitis pigmentosa patients with rhodopsin mutations.”
Ramiro S. Maldonado, MD., the Principal Investigator of the clinical trial and Assistant Professor of Ophthalmology at Duke University Medical Center.
