Sepul Bio completes clinical trial enrollment for its USH2A retinitis pigmentosa treatment

Sepul Bio recently announced that it completed enrollment of its Phase 2b safety and efficacy clinical trial for ultevursen – an investigational RNA therapy to treat patients who have retinitis pigmentosa (RP) associated with mutations in the USH2A gene.

The company exceeded its target of enrolling 81 adults and children above age eight in the global two-year study launched in December 2024. Patients were randomized 2:1 to receive either the treatment or a sham. The team will continue to gather data on safety and how well the treatment worked over the trial’s planned two-year follow-up period.

There are currently no treatments for RP associated with the USH2A gene.  

How ultevursen works to treat RP

Retinitis pigmentosa is an inherited condition that causes light-sensitive cells in the retina – the tissue in the back of the eye – to degenerate, causing vision loss. Although there are many genes that can cause RP, mutations in the USH2A gene are a common cause. Mutations in the USH2A gene can cause RP on its own, or Usher syndrome type 2A, a condition where patients have combined vision and hearing loss, and in some cases, balance dysfunction.

The USH2A gene codes for a protein called usherin, which plays a role in supporting cells in the retina. Mutations in the gene interfere with the production of usherin, leading to cell death that causes vision loss.

Ultevursen targets the USH2A gene and homes in on a specific section called exon 13, a site of many USH2A variants. The potential treatment is an antisense oligonucleotide (ASO) – a single strand of genetic material called RNA – that causes the exon 13 area to be removed entirely from the USH2A RNA, so that it encodes a shorter but still functional usherin protein.

The clinical trial currently underway – called LUNA – will determine if producing this version of the usherin protein in the retina slows photoreceptor cell loss and helps preserve vision in patients with USH2A-associated RP. It is administered by injection into the vitreous, the clear gel that fills the eye, every six months. Patients included in the trial must have two genetic variants in the USH2A gene, and at least one of them must be in exon 13, among other criteria.   

Foundation connection to USH2A

To design the LUNA clinical trial, Sepul Bio used insights from the Foundation’s RUSH2A natural history study, which tracked what USH2A-associated RP looks like in patients over a period of four years. The RD Fund, the venture philanthropy arm of the Foundation Fighting Blindness, invested in the development of ultevursen when the treatment was initially being developed by ProQR Therapeutics. Sepul Bio is a business unit of Laboratories Théa, which acquired ultevursen from ProQR in 2023 and is developing RNA therapies for inherited retinal diseases.

See research advances for retinitis pigmentosa and Usher syndrome for information on other potential treatments making their way through the pipeline.