Low-Dose Atropine Slows Myopia Progression in Children, finds Phase 3 STAR Trial

In children aged 3-12 years, low-dose atropine (SYD-101) significantly reduced myopia progression compared to placebo (0.77 D vs 1.07 D). The effect was even greater in rapid progressors (0.51 D vs 1.18 D). Over 36 months, SYD-101 effectively slowed myopia progression, particularly in younger children and those with faster disease progression.

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 of -0.50 diopters (D) to -6.00 D, with a mean baseline progression of -2.65 D, were enrolled across the U.S. and Europe and randomized (1:1:1) to vehicle (placebo) and SYD-101 0.01%. The study’s primary efficacy endpoint was the proportion of patients with confirmed progression of -0.75 D, and a key secondary endpoint was annual progression rate. SYD-101 0.01% successfully met both the primary endpoint (p<0.001) and the key secondary endpoint. Additionally, SYD-101 was well tolerated with no unexpected atropine-related adverse events.

“The STAR trial is the largest rigorously designed study of low-dose atropine conducted to date. The research was performed in a diverse patient population across 47 clinical sites in the United States and Europe. The subgroup analyses tell an important clinical story: young children with a history of myopia progression benefited most from SYD-101,” said Tina Rutar, MD, pediatric ophthalmologist and partner at Cataract and Laser Institute of Southern Oregon, P.C., and lead author of the AAPOS presentation.

Summary of Key Findings from the AAPOS Presentation

• SYD-101 0.01% significantly reduced myopia progression across all time points tested and met the primary efficacy endpoint at 36 months of confirmed myopia progression of -0.75D or worse (Vehicle vs. 0.01%; p=0.0226).

• SYD-101 0.01% met the key secondary endpoint of mean annual myopic progression rate at 12, 24, and 36 months. At month 36, the APR was -0.30 D/year for 0.01% versus -0.38 D/year for vehicle (p<0.001).

• Treatment benefit of SYD-101 0.01% was highest in younger children compared with older children. In children aged 3 to 12 years at treatment initiation myopia progression was reduced by 47.9% at 12 months, 37.6% at 24 months, and 28.0% at 36 months versus vehicle1.07 D; 0.01% -0.77 D (p=0.0002). Participants aged 13 to 14 years at treatment initiation showed minimal progression regardless of treatment.

• Treatment benefit was greatest in children exhibiting Fast progression (>0.5D year) and with mild to moderate baseline myopia (-0.50D to -3.00D). In this subgroup, SYD-101 0.01% reduced myopia progression by 76.3% at 12 months, 65.1% at 24 months, and 56.9% at 36 months versus vehicle -1.18 D; 0.01% -0.51D (p=0.0004).

• SYD-101 was well tolerated with no unexpected atropine-related adverse events.

“The analyses presented at AAPOS reinforce a growing body of evidence supporting the use of low-dose atropine in PPM,” said Christie Morse, MD, Executive Vice President of the American Association for Pediatric Ophthalmology and Strabismus. “Pediatric myopia is a progressive disease, and the earlier it is identified, the greater the opportunity to intervene in a meaningful way. These findings help clarify which patients stand to benefit most and underscore the importance of timely, evidence-based care to truly change the trajectory of the disease.”

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

“While STAR met both its primary endpoint and a key secondary endpoint, the subgroup analyses presented at AAPOS provide important context for understanding which children benefit most from SYD-101,” said Perry Sternberg, Chief Executive Officer of Sydnexis. “Treatment benefit was observed broadly across the study population, with the most meaningful reductions seen in younger children ages 3-12 and fast progressors which aligns with the known natural history of the disease. These results reinforce the importance of early intervention and are integral to our ongoing discussions with the FDA.”