Aldeyra Therapeutics, Inc. announced positive top-line results from the Phase 2 clinical trial of intravitreal ADX-2191 (methotrexate injection, USP), an investigational drug candidate, in patients with retinitis pigmentosa. Relative to baseline, the clinical trial demonstrated statistically significant improvement in retinal function across a number of different physiological and psychophysical assessments.
“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,” stated Todd C. Brady, MD, PhD, president and CEO of Aldeyra. “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.”
Based on preclinical evidence suggesting that methotrexate may facilitate the clearance of mutated rhodopsin1, a protein critical for visual cycle function, an open-label, single-center phase 2 clinical trial of ADX‑2191 was performed in eight retinitis pigmentosa patients with rhodopsin misfolding mutations.
Over three months of treatment with ADX-2191, four patients received monthly injections and four patients received twice-monthly injections. The primary endpoint of the clinical trial was safety.
Secondary endpoints included change from baseline in visual acuity; retinal function, as assessed by macular and dark-adapted chromatic perimetry and electroretinography; and retinal morphology, as assessed by optical coherence tomography. Visual acuity, perimetry, and morphology assessments were performed monthly for four months from initiation of therapy. Electroretinography was performed at baseline and at 90 days from initiation of therapy.
All enrolled patients completed the trial per protocol. Relative to baseline, across all patients, statistical significance was achieved for improvement in best corrected visual acuity (P<0.0001), low-light visual acuity (P=0.0001), time to electroretinographic response to light (P=0.02), macular sensitivity to light (P<0.0001), and dark-adapted peripheral sensitivity to light (P<0.0001). ADX‑2191 was well tolerated, and no safety concerns were identified. No treatment-related adverse events associated with retinal morphology were observed. No serious adverse events were reported, and no patients discontinued due to adverse events.
“Retinitis pigmentosa is a relentlessly progressive disease that inevitably leads to loss of vision,” stated Ramiro S. Maldonado, MD, the principal Investigator of the clinical trial and Assistant Professor of Ophthalmology at Duke University Medical Center. “The promising results presented today are supportive of a potential novel approach for the treatment of retinitis pigmentosa patients with rhodopsin mutations.”
ADX-2191 is a novel intravitreal formulation of methotrexate in clinical development for proliferative vitreoretinopathy and retinitis pigmentosa, both of which are rare, sight-threatening retinal diseases with no approved therapies. The prevalence of retinitis pigmentosa is more than one million people worldwide, and genetic mutations leading to rhodopsin misfolding account for approximately one-third of cases. ADX-2191 has been granted orphan drug designation by the U.S. Food and Drug Administration for the treatment of proliferative vitreoretinopathy and retinitis pigmentosa.