Ultevursen Advanced Drug Monograph

Ultevursen Report

Name: Ultevursen Name (English): Ultevursen DrugBank ID: DB17835 Type: Biotech (Nucleic Acid) CAS Number: 2642382-41-8

Mechanism of Action: Ultevursen is an antisense oligonucleotide (AON) designed to target exon 13 of the USH2A gene. By binding to the messenger RNA (mRNA) of this gene, ultevursen promotes exon skipping during protein translation. This is intended to restore the production of a functional, albeit shortened, usherin protein in individuals with retinitis pigmentosa (RP) and Usher syndrome type 2A caused by mutations in exon 13 of the USH2A gene.

Clinical Trials: Ultevursen (also known as QR-421a or SB-421a) has been the subject of several clinical trials for the treatment of RP due to mutations in exon 13 of the USH2A gene. These include:

• Stellar (Phase 1/2): A completed study that demonstrated benefits in visual acuity, retinal sensitivity, and retinal structure.
• Sirius (Phase 2/3; NCT05158296): A terminated double-masked, randomized, controlled study evaluating the efficacy, safety, and tolerability of ultevursen in subjects with RP due to mutations in exon 13 of the USH2A gene.
• LUNA (Phase 2b; NCT06627179): An ongoing two-year, double-masked, randomized, sham-controlled study assessing the efficacy, safety, and tolerability of ultevursen in subjects with RP due to mutations in exon 13 of the USH2A gene. This study is actively recruiting adults and children (≥ 8 years old).

Regulatory Status: Ultevursen has been granted the following designations:

• Orphan Drug Designation: in the United States and the European Union for Usher syndromes and retinitis pigmentosa.
• Fast Track Designation: from the FDA in the United States.
• Rare Pediatric Disease Designation: from the FDA in the United States.

Developer: Originally developed by ProQR Therapeutics, the ophthalmology assets, including ultevursen, were acquired by Laboratoires Théa in December 2023. Sepul Bio, a business unit of Laboratoires Théa, is now continuing the clinical development of ultevursen.

Route of Administration: Intravitreal injection.

Indication: Treatment of retinitis pigmentosa and Usher syndrome type 2A in individuals with mutations in exon 13 of the USH2A gene.