Ocumension Therapeutics (Shanghai) Co., Ltd today shared an update on the global landscape of pediatric myopia treatment, emphasizing the growing unmet need for clinically meaningful interventions and the evolving regulatory expectations surrounding low-dose atropine formulations.
Myopia: A Growing Global Public Health Challenge
Myopia has become a major global public health issue, with an estimated worldwide prevalence of 30%. The World Health Organization has identified refractive error correction as a priority, underscoring the need for therapeutic approaches that slow disease progression and axial elongation. While prescription lenses improve vision, they do not address the underlying pathology. Refractive surgery remains limited by cost and eligibility, creating an urgent need for early therapeutic intervention to prevent high myopia and associated risks such as retinal detachment and myopic maculopathy. Low-dose atropine has emerged as a promising option to help reduce these long-term complications.
Atropine’s Clinical Potential in Myopia Management
Atropine has been studied for more than 150 years as a treatment for myopia. Despite its demonstrated efficacy and favorable safety profile in pediatric clinical trials, no drug has yet been approved for myopia progression in either the United States or Europe. A pivotal five-year randomized trial showed that 0.01% atropine offered the most favorable balance of efficacy and tolerability, producing minimal effects on pupil dilation (0.8 mm) and accommodation (2–3 D) compared with higher concentrations.
Regulatory Milestones in 2025: The Case of SYD–101
SYD-101, a novel low-dose atropine formulation (0.01% and 0.03%), recently received a Complete Response Letter from the U.S. Food and Drug Administration. As of 2025, no low-dose atropine product has been approved in the U.S.
The Phase 3 STAR trial, a multicenter, vehicle-controlled study in children ages 3–14 with myopia from –0.50 D to –6.00 D, included a 36-month initial treatment phase followed by a 12-month re-randomization phase. Regulatory endpoints differed by region:
FDA Primary Endpoint: Proportion of patients with confirmed myopia progression worse than –0.75 D at or before Month 36.
EU Primary Endpoint: Difference in mean annual myopia progression rate through Month 24.
The trial was powered to detect a 15% difference for the FDA endpoint and a 0.18 D/year reduction for the EU endpoint.
Trial Outcomes and Regulatory Implications
SYD-101 did not meet the pre-specified thresholds for clinical importance in either region.
For the FDA endpoint, the 0.01% dose showed a –9.6% difference (95% CI: –17.91, –1.26; p=0.0459), short of the 15% requirement.
For the EU endpoint, the 0.01% formulation achieved a statistically significant reduction of 0.132 D/year (p=0.0003), but below the 0.18 D/year benchmark for clinical relevance.
Despite this, the European Medicines Agency (EMA) granted restricted approval for the 0.01% formulation, Ryjunea®, based on a positive benefit-risk assessment in a pre-defined “fast progressor” subgroup (those progressing >0.5 D/year). Approval is limited to this population, and 48-month follow-up data are required post-authorization. EMA reviewers noted concerns regarding long-term efficacy and rebound effects, though these risks are reduced at lower concentrations.
Formulation Differences: SYD–101 and OT–101
The regulatory findings highlight that not all low-dose atropine products are equivalent. Differences in formulation can affect both efficacy and safety outcomes.
SYD-101 uses deuterium oxide (heavy water) as its vehicle and has a pH of 5.4.
In contrast, OT-101 contains atropine sulfate, citric acid, sodium citrate, mannitol, sorbitol, EDTA, and benzalkonium chloride, titrated to a pH of 5.9 using sterile water. OT-101 contains no deuterium, resulting in a formulation closer to neutral pH with minimal impact on viscosity.
These distinctions underscore the importance of formulation science in achieving therapeutically meaningful results.
OT–101 Positioned as a Key Candidate for Clinical Advancement
The regulatory experience of SYD-101 demonstrates that statistical significance alone is insufficient for approval; therapies must also meet predefined thresholds of clinical importance. The inability of SYD-101 to meet both standards, and its subsequent restricted approval in Europe, emphasizes the high development bar for myopia treatments.
In this context, OT-101—built on a distinct and differentiated formulation—continues to advance as a key candidate in clinical development aimed at addressing the significant unmet medical need in slowing pediatric myopia progression.
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