Sydnexis Announces Topline Pivotal Data from Phase 3 STAR Trial of SYD-101

Sydnexis announced topline results from its phase 3 STAR (Study of Atropine for the Reduction of Myopia Progression) trial of SYD-101, a proprietary 0.01% atropine formulation developed with enhanced ocular delivery characteristics and room-temperature stability to slow the progression of myopia in children. These findings were recently presented in a poster session at Academy of Managed Care Pharmacy (AMCP) Nexus 2025 in National Harbor, Maryland.

“The data presented at AMCP Nexus 2025 show strong treatment effects in the full study population at 36 months, but in younger patients, the magnitude of effect gets larger, and in patients with documented faster progression, the magnitude of treatment effect increases even more,” said Perry Sternberg, CEO of Sydnexis. “The STAR data demonstrate that younger kids who historically exhibit fast progression, which is the subpopulation of children at highest risk for severe disease, benefit the most from treatment with SYD-101 0.01%.”

The phase 3 STAR trial is the largest global clinical program completed to date in pediatric myopia. It evaluated a broad population of 847 children aged 3-14 at treatment initiation. Participants with myopia -0.50 D to ‑6.00 D with a mean baseline progression of -2.65 D were enrolled across the United States and Europe and randomized (1:1:1) to vehicle (placebo), SYD-101 0.01%, or SYD-101 0.03%. The study’s primary efficacy endpoint was proportion of patients with confirmed progression of -0.75 D, an endpoint proposed by the FDA, and a key secondary endpoint was annual progression rate. SYD-101 0.01% successfully met both the primary and key secondary endpoints. Additionally, SYD-101 was well tolerated with no unexpected atropine-related adverse events.

“Findings from the STAR trial, which is the largest pediatric myopia study to date, reinforce the importance of early intervention, both in terms of patient age and disease progression,” said Christie Morse, MD, executive vice president of the American Association for Pediatric Ophthalmology and Strabismus. “The results highlight the potential of low-dose atropine to help preserve children’s vision over time, a meaningful step forward in how we approach the management of this increasingly prevalent condition.”

“Compounded low-dose atropine has posed challenges from both an access and a consistency standpoint. SYD-101’s unique formulation of atropine, which has been well-researched and supported by the results of the STAR trial, could be a valuable treatment option to help protect children’s vision and improve long-term outcomes,” said Kevin Chan, OD, MS, FAAO, senior clinical director of Treehouse Eyes.

SYD-101 is currently approved in the European Union, where it is licensed to Santen SA. and marketed as Ryjunea.

Summary of Key Topline Findings:

• In the full study population, SYD-101 0.01% met its primary efficacy endpoint of proportion of patients with confirmed progression of -0.75 D at 36 months versus vehicle (139 vs 111 patients [vehicle vs. 0.01%]; P = .0226).
• Additionally, SYD-101 0.01% met its key secondary endpoint, mean myopic annual progression rate, in the full study population at month 36 (vehicle: -0.38 D/year vs. 0.01%: -0.30 D/year [P = .0002]).
• The primary efficacy and key secondary endpoints were met even though 36% of the total patients in the SYD-101 0.01% arm were aged 16-18 and exhibited very little progression by the end of the study.
• In the pre-specified analysis of change from baseline spherical equivalent, SYD-101 0.01% and 0.03% had significantly smaller changes compared with vehicle in the full study population at month 36 (vehicle: ‑0.92 D; 0.01%: -0.71 D [P -.0022]; 0.03%: 0.76 D [P = .0158]).
• Data presented at AMCP also showed that the magnitude of clinical effect of change in spherical equivalent was even larger in younger patients (3-12 years old at treatment initiation), with both doses demonstrating nominal statistical significance (vehicle: ‑1.07 D; 0.01%: -0.77 D [P -.0002]; 0.03%: 0.85 D [P = .0065]).
• Also presented was data in a subgroup of fast progressors (more than -0.5 D/year progression prior to the study) at 36 months. In these patients with low to moderate myopia (-0.50 D to -3.00 D) at study initiation, SYD-101 0.01% reduced the progression by more than 50% (vehicle: -1.18 D; 0.01%: -0.51 D [P = .0004]; 0.03%: -0.92 D [P -.1505]), highlighting the importance of early disease modifying intervention in childhood myopia.

“The STAR study is an extremely important contribution to the growing body of evidence supporting low-dose atropine as a therapeutic option for pediatric progressive myopia and reinforces the unmet need eye care practitioners see in the field every day,” said Patrick Johnson, PhD, president of Sydnexis. “SYD-101 can meaningfully slow the trajectory of this disease and would be a welcome improvement to the compounded products that lack adequate quality oversight that are currently being used chronically in kids.”