ADX-2191 receives EM orphan drug designation for inherited retinal dystrophies

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In a press release, Aldeyra Therapeutics, Inc. announced that the European Medicines Agency (EMA) has granted orphan designation for its methotrexate intravitreal injection (ADX-2191). The therapeutic candidate is formulated for the treatment of inherited retinal dystrophies, including retinitis pigmentosa (RP). ADX-2191 is being investigated for performance in inherited retinal diseases of the rod-dominant phenotype.¹

In 2021, the United States Food and Drug Administration granted orphan drug designation to ADX-2191.² The phase 2 trial supporting the EMA's decision this week was originally announced in 2023. Data from that trial demonstrated improvements from baseline in retinal sensitivity. The company, based in Lexington, Massachusetts, plans to initiate a phase 2/3 trial further examining ADX-2191 for RP later in 2025.

In the European Union, orphan designation grants companies a number of benefits: reduced regulatory fees, research grants, clinical protocol support, and potential long-term market exclusivity throughout the EU. The EMA grants orphan designation to drugs/biologics intended to address life-threatening or chronically debilitating diseases that affect fewer than five in 10,000 EU residents.¹

Todd C. Brady, MD, PhD, president and CEO of Aldeyra Therapeutics, said the orphan designation will expand access to therapies for RP and other inherited retinal dystrophies. “Retinitis pigmentosa is a serious and incurable sight-threatening disease that represents a major unmet need in the field of ophthalmology,” Brady said in the press release.¹ “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.”

Currently, there are no approved treatments for RP, a group of genetic eye diseases characterized by retinal cell death and subsequent loss of visual acuity. In the press release, Aldeyra Therapeutics provided information about the functional utility of its methotrexate intravitreal injection. In vivo preclinical research identified methotrexate as an agent to induce misfolded rhodopsin clearance. Rhodopsin, a protein found in the rod cells, is light-sensitive and crucial to the visual cycle. ADX-2191 is a sterile, non-compounded intravitreal formulation of methotrexate that is preservative-free and vitreous-compatible. The US FDA's orphan drug designation applies to the use of ADX-2191 in the treatment of RP and primary vitreoretinal lymphoma.

Aldeyra Therapeutics designs pharmaceuticals that modulate protein systems, rather than functioning with a protein inhibitor/activator model. Along with ADX-2191, the company's other late-stage product candidate is reactive aldehyde species (RASP) modulator reproxalap, indicated as a potential therapy for dry eye disease and allergic conjunctivitis. Other product candidates from the company include RASP modulators ADX-629, ADX-248, ADX-743, ADX-631, and ADX-246.

References

1. Aldeyra Therapeutics Receives Orphan Designation from the European Medicines Agency for ADX-2191 for the Treatment of Inherited Retinal Dystrophies including Retinitis Pigmentosa. Press release. Aldeyra Therapeutics. Published July 24, 2024. Accessed July 24, 2025. https://www.businesswire.com/news/home/20250724869031/en/Aldeyra-Therapeutics-Receives-Orphan-Designation-from-the-European-Medicines-Agency-for-ADX-2191-for-the-Treatment-of-Inherited-Retinal-Dystrophies-including-Retinitis-Pigmentosa
2. Kaiser Maharjan E. U.S. FDA grants orphan drug designation to ADX-2191 from Aldeyra Therapeutics. Ophthalmology Times Europe. Published August 5, 2021. Accessed July 24, 2025. https://europe.ophthalmologytimes.com/view/u-s-fda-grants-orphan-drug-designation-to-adx-2191-from-aldeyra-therapeutics