Aldeyra Therapeutics Receives EMA Orphan Drug Designation for ADX-2191 in Retinitis Pigmentosa

Aldeyra Therapeutics has announced that the European Medicines Agency (EMA) has granted orphan drug designation to ADX-2191, its methotrexate intravitreal injection. ADX-2191 is being developed as a potential treatment for inherited retinal dystrophies, specifically targeting rod-dominant diseases such as retinitis pigmentosa (RP).

This regulatory milestone follows the orphan drug designation granted by the U.S. Food and Drug Administration (FDA) in 2021. The EMA’s decision is based on data from a Phase 2 clinical trial announced in 2023, which showed improvements in retinal sensitivity from baseline. Aldeyra intends to initiate a Phase 2/3 trial of ADX-2191 for RP later in 2025.

Clinical Background and Regulatory Benefits

RP is a progressive, inherited retinal disease that leads to vision loss through degeneration of rod photoreceptors. There are currently no approved therapies for RP, a condition that remains a major unmet need in ophthalmology. ADX-2191 is a sterile, preservative-free, vitreous-compatible formulation of methotrexate, designed specifically for intravitreal injection. Preclinical studies have identified methotrexate’s ability to promote the clearance of misfolded rhodopsin, a light-sensitive protein essential to visual function.

In the European Union, orphan designation provides key incentives, including reduced regulatory fees, access to research grants, clinical protocol assistance, and up to 10 years of market exclusivity upon approval. Orphan status is reserved for therapies addressing life-threatening or chronically debilitating conditions affecting fewer than five in 10,000 individuals across the EU.

Executive Remarks and Development Plans

Commenting on the designation, Aldeyra’s President and CEO Todd C. Brady, MD, PhD, emphasized the potential impact of ADX-2191:

“Retinitis pigmentosa is a serious and incurable sight-threatening disease that represents a major unmet need in the field of ophthalmology,” he stated. “The receipt of orphan designation from the EMA, in conjunction with the previously announced orphan drug designation from the US Food and Drug Administration, highlights the importance of developing a treatment option for patients suffering from retinitis pigmentosa.”

Pipeline Overview

In addition to ADX-2191, Aldeyra’s late-stage pipeline includes reproxalap, a reactive aldehyde species (RASP) modulator currently in development for dry eye disease and allergic conjunctivitis. Other investigational RASP modulators include ADX-629, ADX-248, ADX-743, ADX-631, and ADX-246. The company’s approach centers on modulating protein systems rather than directly inhibiting or activating them, offering a novel strategy in therapeutic development.