Aldeyra Achieves Primary Endpoint in Part 1 of Phase 3 Trial in Rare Eye Disease

Aldeyra Therapeutics reported that it achieved the primary endpoint in Part 1 of its phase 3 GUARD trial of ADX-2191, its experimental therapy for prevention of the rare retinal disease proliferative vitreoretinopathy.

Photo: Marco Zarbin, professor and chair of the Institute of Ophthalmology and Visual Science, Rutgers New Jersey Medical School

The company said ADX-2191, a sterile, non-compounded intravitreal formulation of methotrexate, was statistically superior to historical control for the prevention of retinal detachment due to proliferative vitreoretinopathy over six months.

Proliferative vitreoretinopathy (PVR) is a rare inflammatory fibroproliferative disorder that leads to severe retinal scarring and blindness and is the leading cause of failure of retinal reattachment surgery. Left untreated, retinal detachment due to PVR can progress to permanent blindness. PVR affects approximately 4,000 patients per year in the United States. There is currently no approved therapy for the treatment of PVR.

“Proliferative vitreoretinopathy represents a major unmet medical need and is particularly difficult to treat, highlighting the need for an effective therapy,” said Marco Zarbin, professor and chair of the Institute of Ophthalmology and Visual Science at Rutgers New Jersey Medical School. “The recent reports describing the activity of methotrexate in preventing PVR, in conjunction with the results of the GUARD trial, offer hope to many patients and physicians that today have few options for treatment.”

Part 1 of the GUARD trial was designed to assess the preliminary activity of ADX-2191, a novel vitreous-compatible formulation of methotrexate, versus historical control and routine surgical care without therapy in patients with PVR. Sixty-eight patients received ADX-2191, and 38 patients received routine surgical care. Relative to historical control, statistically significant reduction in retinal detachment over six months was observed following serial intravitreal injection of ADX-2191.

Although not statistically powered for secondary or exploratory endpoints, the results of the GUARD trial demonstrated numerical superiority of ADX-2191 over routine surgical care in reducing the dichotomous endpoints of retinal detachment rate over six months, hypotony (low intraocular pressure), complete retinal attachment by six months, macular attachment by six months, and epiretinal membrane formation. Visual acuity was similar between ADX-2191 treatment and routine surgical care groups. Central macular thickness was numerically lower in ADX-2191-treated patients.

No safety signals were observed in the trial, and ADX-2191 was well tolerated; there were no observed treatment-emergent serious adverse events. The most common adverse event associated with ADX-2191 treatment was punctate keratitis, a well-known side effect of intravitreal methotrexate, which was most commonly mild in severity. Across all other treatment-emergent adverse events occurring in at least 10 percent of patients in either treatment arm, relative to patients treated with routine surgical care, ADX-2191-treated patients had numerically fewer side effects, including pain, cystoid macular edema, corneal edema, macular fibrosis, corneal epithelial defects, anterior uveitis, ocular hypertension, and post-operative inflammation. In the ADX-2191 group, there was one discontinuation, which was due to scheduling difficulties.

Aldeyra intends to discuss completion of clinical development of ADX-2191 for the prevention of PVR in a Type C meeting with the U.S. Food and Drug Administration in the first half of 2023. ADX-2191 has received FDA Orphan Drug and Fast Track designations for the prevention of PVR, and EU Orphan Medicinal Product designation for the treatment of retinal detachment. ADX-2191 has also received FDA Orphan Drug designation for the treatment of primary vitreoretinal lymphoma and retinitis pigmentosa.

Author: Rare Daily Staff