Atsena Therapeutics' novel gene therapy ATSN-201 has received both Orphan Drug and Rare Pediatric Disease designations from the U.S. Food and Drug Administration (FDA) for the treatment of X-linked retinoschisis (XLRS), a rare genetic disorder that causes vision loss primarily in males.
These regulatory milestones represent significant advancement for patients with XLRS, a condition for which no approved treatments currently exist. The designations could accelerate the development pathway and, if approved, ATSN-201 would become the first therapy addressing the underlying genetic cause of the disease.
"There are currently no approved treatments for X-linked retinoschisis," Patrick Ritschel, CEO of Atsena, told Healio. "If approved, ATSN-201 would be the first time that ophthalmologists could offer a therapy to their patients with XLRS to address the underlying genetic cause of the disease."
Understanding X-Linked Retinoschisis
XLRS is a rare inherited retinal disorder characterized by splitting (schisis) of the retina's layers, resulting in reduced visual acuity due to juvenile macular degeneration. The condition is caused by mutations in the RS1 gene located on the X chromosome, which provides instructions for producing retinoschisin, a protein essential for retinal development and maintenance.
The disease typically manifests in the first decade of life, with symptoms including poor vision and reading difficulties. XLRS has an estimated prevalence ranging from 1 in 5,000 to 1 in 25,000 males worldwide. Ophthalmologists can often identify the condition by a characteristic 'spoke-wheel' pattern in the macula during eye examinations.
XLRS generally progresses slowly until adolescence, stabilizes during young adulthood, and may decline again in the fourth or fifth decade of life. In severe cases, patients may experience full-thickness retinal detachment, vitreous hemorrhage, and neovascular glaucoma, leading to significant vision loss.
Innovative Therapeutic Approach
ATSN-201 represents a potentially transformative approach to treating XLRS. The gene therapy utilizes AAV.SPR, a novel spreading capsid developed by Atsena Therapeutics, to deliver functional copies of the RS1 gene to affected cells in the retina.
What distinguishes this approach is the capsid's ability to achieve therapeutic levels of gene expression in retinal photoreceptors while avoiding the risks associated with foveal detachment. The spreading capability of AAV.SPR allows the therapy to extend beyond the immediate injection site, potentially treating a larger area of the retina than traditional adeno-associated virus vectors.
"With its ability to spread beyond the margins of the subretinal injection bleb, AAV.SPR could make it possible to deliver gene therapies to a much larger area of the retina than traditional [adeno-associated viruses]," Ritschel explained. This technology may "potentially open the doors to developing treatments for a broad range of inherited retinal diseases that have otherwise been untreatable with subretinal injection."
Clinical Development and Preliminary Results
The LIGHTHOUSE study, a Phase 1/2 clinical trial, is currently evaluating the safety and efficacy of ATSN-201 in male patients with XLRS. The trial is initially enrolling adult participants, with plans to include pediatric patients aged 6 to 17 years after collecting sufficient safety and efficacy data in adults.
Preliminary data from the first cohort has shown encouraging results. Two out of three patients experienced extensive schisis resolution beginning at 8 weeks post-treatment. Importantly, the therapy demonstrated lateral spread beyond the injection sites, consistent with the expected behavior of the AAV.SPR capsid.
"We are hopeful that we will see schisis resolution (i.e., improvements in the structure of the retina) with ATSN-201 and also improvements in visual function for these patients," Ritschel said.
Regulatory Implications
The Orphan Drug Designation is granted to therapies addressing conditions affecting fewer than 200,000 people in the United States and provides benefits including tax credits for clinical trials, exemption from user fees, and potential market exclusivity upon approval.
The Rare Pediatric Disease Designation means that upon approval, Atsena would receive a priority review voucher that could be used to advance another program in their pipeline or be sold. This voucher allows for expedited review of a subsequent marketing application, potentially reducing the standard review time.
These designations highlight the FDA's recognition of both the significant unmet medical need in XLRS and the potential of ATSN-201 to address this challenging condition. For patients and families affected by XLRS, these regulatory milestones represent meaningful progress toward a potential first-in-class treatment option for a previously untreatable genetic eye disorder.
