Aldeyra Therapeutics Achieves Primary Endpoint in Part 1 of Phase 3 GUARD Trial of ADX-2191 in Proliferative Vitreoretinopathy

Aldeyra Therapeutics announced the achievement of the primary endpoint in Part 1 of the phase 3 GUARD Trial of ADX-2191 (methotrexate injection, USP¹) for intravitreal administration, an investigational drug candidate, for the prevention of proliferative vitreoretinopathy (PVR). ADX-2191 was statistically superior to historical control² for the prevention of retinal detachment due to PVR over 6 months (P=0.024).

“Proliferative vitreoretinopathy represents a major unmet medical need and is particularly difficult to treat, highlighting the need for an effective therapy,” Marco Zarbin, MD, PhD, Professor and Chair of the Institute of Ophthalmology and Visual Science, Rutgers New Jersey Medical School, said in a company news release. “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 (P=0.024) in retinal detachment over 6 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 6 months, hypotony (low intraocular pressure), complete retinal attachment by 6 months, macular attachment by 6 months, and epiretinal membrane formation (overall P=0.047). 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, that was most commonly mild in severity. Across all other treatment-emergent adverse events occurring in at least 10% 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 (overall P=0.0002). 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 FDA in the first half of 2023. ADX-2191 has received FDA Orphan Drug Designation and FDA Fast Track Designation 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.

“The ADX-2191 platform for the prevention and treatment of rare retinal disease continues to advance towards commercialization, and is a critical late-stage pipeline program with the potential to address a number of diseases with no FDA-approved therapies,” stated Todd C. Brady, MD, PhD, President and Chief Executive Officer of Aldeyra.