Phase 3 STAR trial data show SYD-101 met primary, secondary end points in pediatric myopia

Sydnexis has announced new data from subgroup analyses of the phase 3 Study of Atropine for the Reduction of Myopia Progression (STAR) trial of SYD-101. The findings were presented during an oral session at the 51st Annual Meeting of the American Association for Pediatric Ophthalmology and Strabismus (AAPOS) in Boston, Massachusetts.

The Phase 3 STAR trial evaluated 847 children aged 3–14 at treatment initiation and is described as the largest global clinical program completed to date in pediatric myopia. Participants with myopia of -0.50 diopters (D) to -6.00 D and a mean baseline progression of -2.65 D were enrolled across the US and Europe and randomized (1:1:1) to vehicle (placebo) or SYD-101 0.01%. The 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% met both the primary endpoint (p<0.001) and the key secondary endpoint and was reported to be 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, PC, and lead author of the AAPOS presentation, in the release.

According to the 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 -0.75 D or worse (vehicle vs. 0.01%; p=0.0226). The treatment also met the key secondary endpoint of mean annual myopic progression rate at 12, 24, and 36 months. At month 36, the annual progression rate was -0.30 D/year for SYD-101 0.01% compared with -0.38 D/year for vehicle (p<0.001).¹

Subgroup analyses indicated that treatment benefit was greater in younger children. Among those 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 vehicle (-1.07 D; 0.01%, -0.77, p=0.0002). Participants aged 13 to 14 years showed minimal progression regardless of treatment.¹

Greater effects were also observed in children with faster progression (>0.5 D/year) and mild to moderate baseline myopia (-0.50 D to -3.00 D). 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% -0.51 D; p=0.0004). SYD-101 was reported to be well tolerated with no unexpected atropine-related adverse events.¹

“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, in the release. “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 approved in the European Union and the UK, where it is licensed to Santen SA 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, CEO of Sydnexis, in the release. “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.”

The oral presentation, titled “The Study of Atropine to Reduce (STAR) Myopia Progression in Children: A Randomized, Double-Masked Clinical Trial of Low-Dose Atropine,” was presented March 21 at 8:30 am ET by Tina Rutar, MD, on behalf of the STAR Study Group.

SYD-101 is a proprietary low-dose atropine formulation developed to slow the progression of pediatric progressive myopia. It has demonstrated enhanced ocular tissue permeability in preclinical animal models compared to other formulations, is stable for up to 3 years at room temperature, and has a near-neutral pH that may contribute to ocular safety and comfort.