Key Takeaways

  • Six of 9 patients receiving the ATSN-201 dose selected for phase 3 met the microperimetry response criterion, while 7 of 9 responded on microperimetry and/or visual acuity
  • ATSN-201 demonstrated a favorable preliminary safety profile in Parts A and B, with no drug-related serious adverse events or dose-limiting toxicities reported
  • Atsena expects to complete enrollment in the pivotal phase 3 portion of LIGHTHOUSE by the end of Q1 2027, with topline results anticipated in the first half of 2028

Atsena Therapeutics reported preliminary safety and efficacy findings for its investigational gene therapy ATSN-201 in patients with X-linked retinoschisis (XLRS), with 6 of 9 patients treated at the dose selected for phase 3 meeting the study's microperimetry response criterion.

The findings from Parts A and B of the phase 1/2/3 LIGHTHOUSE Study are being presented at the American Academy of Ophthalmology (AAO) 2026 Annual Meeting, held October 9 to 12 in New Orleans.

Atsena is advancing the 1.1E10 vg/eye dose into Part C, the pivotal phase 3 portion of LIGHTHOUSE. The company said enrollment is expected to be completed by the end of the first quarter of 2027, with topline results anticipated in the first half of 2028.

“Data presented this week at AAO and last week at the American Academy of Optometry annual meeting show that ATSN-201 has the potential to provide clinically meaningful benefit to patients with XLRS,” Kenji Fujita, MD, chief medical officer of Atsena Therapeutics, said in a news release.

According to Dr. Fujita, the majority of patients treated at the pivotal dose achieved microperimetry improvements exceeding 7 dB across at least 5 loci, an outcome the company said the FDA has identified as supportive of approval. Improvements in retinal structure and visual acuity were also reported.

Phase 1/2 findings

Thomas S. Aleman, MD, of the Scheie Eye Institute and Children's Hospital of Philadelphia, presented 12-month safety and efficacy findings for adult participants and 6-month findings for pediatric participants enrolled in Parts A and B of LIGHTHOUSE.

ATSN-201 was administered by subretinal injection to 1 eye per patient. Parts A and B enrolled 21 patients overall, including 18 who received treatment—15 adults and 3 pediatric patients—and 3 untreated adult controls.

Part A evaluated 3 ATSN-201 doses in cohorts of 3 adults each. Part B assessed 2 dose volumes in adult cohorts, along with an untreated adult control cohort and a pediatric cohort treated at the lower volume.

According to Atsena, ATSN-201 demonstrated a favorable safety profile across participants, with no drug-related serious adverse events or dose-limiting toxicities reported.

Efficacy assessments included foveal schisis closure on optical coherence tomography (OCT), microperimetry, best-corrected visual acuity (BCVA), and low-luminance visual acuity (LLVA).

Microperimetry response, which serves as the primary endpoint for the pivotal phase 3 portion of LIGHTHOUSE, was defined as an average improvement of at least 7 dB across central qualifying loci. Visual acuity response was defined as an improvement of at least 10 letters in either BCVA or LLVA.

Investigators observed structural and functional responses at each of the 3 doses evaluated in Part A. The lowest dose, 1.1E10 vg/eye, was selected for phase 3 based on what the company described as consistent efficacy and more favorable tolerability compared with the higher doses.

Among the 9 patients treated at the pivotal dose across Parts A and B, 7 demonstrated a response on at least 1 of the 2 visual function measures: microperimetry or visual acuity.

Six of 9 patients met the microperimetry response criterion, 5 of 9 were OCT responders, and 3 of 9 were visual acuity responders. None of the 9 untreated fellow eyes met response criteria for OCT, microperimetry, or visual acuity, according to the company.

Across all 18 treated patients in Parts A and B, 13 demonstrated a response on at least 1 visual function measure. Twelve were OCT responders, 9 were microperimetry responders, and 9 were visual acuity responders.

Among the 18 untreated fellow eyes, 1 met the microperimetry response criterion and 1 was a visual acuity responder; none were OCT responders. Among the 3 untreated control patients, none were OCT or microperimetry responders, while 1 met the visual acuity response criterion.

Visual acuity and durability findings

A separate analysis examined BCVA among the 8 of 9 pivotal-dose patients whose baseline visual acuity was worse than 20/40. At their most recent assessments, 3 had achieved visual acuity of 20/40 or better, which the company noted is a threshold commonly associated with driving eligibility in the United States.

Of the remaining 5 patients, 3 showed improvement in visual acuity and 2 remained unchanged from baseline. Atsena also reported longer-term findings from the earliest-treated patient receiving the pivotal dose. That patient reached 3 years of follow-up in July 2026 after a single administration of ATSN-201.

At 36 months, the patient's foveal schisis remained closed, while improvements of 12 dB in microperimetry, 19 letters in BCVA, and 22 letters in LLVA were maintained, according to the company.

“These results give us confidence in the dose now advancing through Part C, the pivotal Phase 3 portion of the LIGHTHOUSE Study,” Dr. Fujita said.

Part C enrollment is expected to conclude by the end of the first quarter of 2027. Atsena anticipates topline phase 3 results in the first half of 2028 and said the data could support a potential biologics license application filing in the second half of 2028.