The FDA has issued a complete response letter (CRL) to Sydnexis Inc. regarding its new drug application for SYD-101, a 0.01% atropine formulation aimed at slowing the progression of pediatric myopia. The decision comes despite the company's Phase 3 trial meeting its primary efficacy endpoint, highlighting the regulatory challenges facing treatments for this rapidly growing childhood eye condition.
Clinical Trial Results and FDA Assessment
The company's NDA was supported by data from the Phase 3 Study of Atropine for the Reduction of Myopia Progression (STAR) trial, described as the most comprehensive global study addressing myopia progression in children. The trial enrolled over 800 children aged 3 to 14 at treatment initiation and successfully achieved its primary efficacy goal, measuring the proportion of participants showing confirmed myopia progression of -0.75 D, a benchmark recommended by the FDA.
Key secondary outcomes demonstrated statistically significant improvements in the annual rate of progression at 12, 24, and 36 months. In a subgroup of fast progressors, defined as more than -0.5 D per year, the low-dose atropine formulation showed a statistically significant reduction in myopia progression exceeding 50% at 36 months.
Despite acknowledging that the primary efficacy endpoint had been achieved, the FDA concluded that the evidence did not demonstrate the effectiveness of low-dose atropine for treating myopia in children. The agency identified no deficiencies concerning safety or product quality.
Company Response and Market Impact
"While we are surprised and disappointed with this decision, Sydnexis is committed to working with the FDA to address the items outlined in the CRL and determining the best path forward toward approval for SYD-101," said Sydnexis CEO Perry Sternberg. The company aims to provide eye care professionals in the US with the first FDA-approved option to help slow pediatric myopia progression, rather than continued reliance on compounded atropine formulations.
Expert Perspectives on Clinical Need
"Myopia has increased during the past few decades and is expected to continue to rise; half of the world's population may be nearsighted by 2050," said Michael X. Repka, MD, pediatric ophthalmologist and president of the American Academy of Ophthalmology. He emphasized that increased myopia represents more than just a need for corrective lenses, as people with high levels of myopia face higher risks for vision-threatening complications including retinal detachments, myopic macular degeneration, cataracts, and glaucoma.
Mark A. Bullimore, FCOptom, PhD, FAAO, adjunct faculty at the University of Houston College of Optometry, described the delay as "disappointing and limits myopia control options for patients and practitioners alike." He noted that the clinical trial met its primary endpoint, making the FDA decision surprising.
European Approval and Global Development
In contrast to the US regulatory outcome, SYD-101 received European Commission marketing authorization in June 2025, becoming the first approved pharmaceutical option for managing myopia progression in EU countries. The European Medicines Agency's Committee for Medicinal Products for Human Use issued a positive recommendation in April 2025. Under a licensing agreement, Santen SA markets the treatment across Europe, the Middle East, and Africa under the brand name Ryjunea.
Disease Burden and Unmet Medical Need
Pediatric Progressive Myopia represents the most common eye disease in children and a rapidly rising global health concern. Nearly one-third of children worldwide are affected by this degenerative disease, with prevalence projected to exceed 740 million cases by 2050. In North America, myopia prevalence is expected to reach nearly 60% by 2050.
The most rapid disease progression occurs in children ages 3 to 10 years, with patients who start progressing younger experiencing more severe outcomes and associated co-morbidities. Despite its growing prevalence, no FDA-approved pharmaceutical options currently exist in the United States to slow PPM progression, representing a significant treatment gap.
Sydnexis announced FDA acceptance of its NDA for SYD-101 in March 2025, with an original PDUFA date of October 23, 2025. The company now faces the challenge of addressing FDA concerns while maintaining its commitment to bringing the first approved myopia control treatment to US patients.
