Atsena Therapeutics’ Makes Progress With X-Linked Retinoschisis Gene Therapy Trial
The company’s phase 1/2 LIGHTHOUSE clinical trial for ATSN-201 has moved onto its Part B.
Atsena Therapeutics has launched Part B of its phase 1/2 LIGHTHOUSE clinical trial (NCT05878860) evaluating ATSN-201, an investigational adeno-associated virus (AAV) gene therapy, for the treatment of X-linked retinoschisis (XLRS) associated with mutations in the RS1 gene.1
ATSN-201 utilizes the company’s AAV.SPR capsid, which is intended to spread laterally from the subretinal injection site, to provide gene expression in the central retina. The central retina, the main area for disease activity in XLRS, would otherwise need to be reached with risky detachment of the fovea through surgery.2 Atsena has noted that in preclinical research in nonnhuman primates, AAV.SPR effected transgene expression well outside the subretinal injection bleb margins, setting it apart from what is seen with benchmark vector AAV5.
“A major benefit of ATSN-201 is that it does not need to be precisely placed underneath a specific retinal region,” Kenji Fujita, MD, Atsena’s Chief Medical Officer, said in a statement.1 “This gives surgeons more discretion regarding bleb placement during subretinal surgery and allows for safe delivery of the healthy gene to the critical portion of the retina. By testing different volumes in Part B, we will better understand the optimal administration of ATSN-201 to achieve the broadest effect.”
Atsena stated that Part B of LIGHTHOUSE will utilize a dose of 1.0x1011 vg/mL of ATSN-201, which the study’s Data Monitoring Committee recommended based on preliminary results from Part A of the trial, which evaluated 3 dose levels. Part B will treat 9 adults and 3 children at this dose level, which the preliminary results from Part A indicate provides an optimal balance of efficacy and safety, according to the company. The cohort for adult patients will be further divided into a low volume arm, a high volume arm, and a control arm. Patients who receive the control may choose to receive ATSN-201 after 1 year of observation. The pediatric group will be treated after preliminary results from the adults in Part B have been obtained and assessed. Microperimetry, visual acuity, and macular structure will be among the outcome measures used in Part B.
“We are pleased to initiate Part B of the LIGHTHOUSE study of ATSN-201 following successful enrollment and dosing of Part A,” Patrick Ritschel, the chief executive officer of Atsena Therapeutics, added to the statement.1 “The functional and structural improvements seen in Part A validate our novel AAV.SPR spreading capsid. Importantly, Part B will enroll both adult and pediatric participants. The rare pediatric disease designation (RPDD) granted for ATSN-201 highlights the unmet need for a treatment, and we remain focused on advancing a therapeutic option for these patients.”
ATSN-201 received RPDD from the FDA in August 2024.3 It also received orphan drug designation from the FDA in September 2024.4
Atsena announced data from the first, low-dose cohort of LIGHTHOUSE in May 2024.5 Notably, among the first 3 participants dosed, there were no serious adverse events. Furthermore, 2 of the 3 patients experienced extensive resolution of schisis beginning at 8 weeks after receiving ATSN-201 and continuing and deepening through week 24 of follow-up until data cut off. The investigators found that areas of schisis cavity resolution were found both inside and well outside of the subretinal injection blebs, demonstrating a lateral spread of the capsid.
“The favorable safety profile and early efficacy observed in patients treated with ATSN-201 in the low- dose cohort of the LIGHTHOUSE study are very encouraging,” Fujita said in a May 2024 statement.5 “We’re particularly pleased to have clinical validation of AAV.SPR’s ability to spread laterally well beyond the subretinal injection blebs.”
