Sydnexis Reports Positive Phase 3 Results for SYD-101

Sydnexis has announced topline results from its pivotal Phase 3 STAR trial (Study of Atropine for the Reduction of Myopia Progression), evaluating SYD-101, a proprietary 0.01% atropine formulation developed to slow myopia progression in children. The results were presented at AMCP Nexus 2025, reinforcing the clinical potential of SYD-101 as a low-dose, room-temperature-stable, and well-tolerated treatment option for pediatric myopia.

STAR Trial Overview

The STAR trial represents the largest global clinical study to date in pediatric myopia, enrolling 847 children aged 3–14 across the United States and Europe. Participants with myopia ranging from -0.50 D to -6.00 D and a mean baseline progression of -2.65 D were randomized (1:1:1) to receive SYD-101 0.01%, SYD-101 0.03%, or vehicle (placebo). The study evaluated:

• Primary efficacy endpoint: Proportion of patients with confirmed myopic progression of ≥ -0.75 D at 36 months (per FDA guidance)

• Key secondary endpoint: Mean annual myopia progression rate

SYD-101 Demonstrates Statistically Significant Efficacy

SYD-101 0.01% successfully met both its primary and secondary endpoints:

• Primary endpoint: Fewer patients progressed by -0.75 D at 36 months in the 0.01% arm compared to vehicle (139 vs. 111; P = .0226)

• Annual progression rate: 0.01% slowed progression to -0.30 D/year vs. -0.38 D/year in vehicle (P = .0002)

• Change in spherical equivalent: At month 36, 0.01% and 0.03% arms showed significantly smaller changes vs. vehicle (vehicle: 0.92 D; 0.01%: -0.71 D, P = .0022; 0.03%: -0.76 D, P = .0158)

Notably, 36% of patients in the 0.01% group were aged 16–18, a population with naturally slower progression, yet endpoints were still met, highlighting the drug's robustness.

Enhanced Benefit in Younger and Fast-Progressing Children

Further analysis revealed even greater efficacy in younger patients (ages 3–12 at baseline):

• Spherical equivalent change: Vehicle: 1.07 D; 0.01%: -0.77 D (P = .0002); 0.03%: -0.85 D (P = .0065)

In a subgroup of fast progressors (pre-study rate > -0.50 D/year), SYD-101 0.01% reduced progression by over 50%:

• Vehicle: -1.18 D; 0.01%: -0.51 D (P = .0004)

“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%,” said Perry Sternberg, CEO of Sydnexis.

“Findings from the STAR trial reinforce the importance of early intervention, both in terms of age and disease progression,” said Dr. Christie Morse, EVP, 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.”

Regulatory and Commercial Outlook

SYD-101 is already approved in the EU, where it is marketed as Ryjunea through a licensing agreement with Santen SA. Its robust data package may position it for broader regulatory submissions, particularly in the U.S., where interest in safe, effective treatments for pediatric myopia continues to rise.

“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,” said Patrick Johnson, PhD, President of Sydnexis.