Rejection of Myopia Drug Raises Questions About Regulatory Consistency
FDA’s recent decision to reject a low-dose atropine treatment for pediatric myopia — despite a large clinical trial meeting pre-specified safety and efficacy benchmarks — has renewed debate over regulatory standards, evidentiary thresholds, and predictability in pediatric drug approvals, according to a Washington Post opinion article. The action was outlined in a 10/2025 complete response letter to Sydnexis for its SYD-101 low-dose atropine eye drop, seeking an indication for slowing the progression of myopia in children. In the letter, the agency acknowledged that the product raised no safety concerns and met predefined measures of effectiveness, but concluded that the magnitude of benefit was insufficient to support approval, writes American Association for Pediatric Ophthalmology and Strabismus president and Harvard professor David G. Hunter.
Data to support SYD-101’s approval came from a single, three-year global clinical trial involving more than 800 pediatric patients, the largest study conducted to date in pediatric myopia. According to the company and clinicians familiar with the review process, FDA had previously advised that one well-designed pivotal trial would be sufficient to support an application, Hunter says.
Myopia, or nearsightedness, affects about 40% of Americans, a figure that has nearly doubled over the past three decades. Epidemiological projections suggest prevalence could approach 60% by 2050. In children, progressive myopia is associated with an increased lifetime risk of retinal detachment, myopic macular degeneration, glaucoma, and cataracts.
Low-dose atropine therapies are already widely used outside the U.S. Pharmaceutical-grade atropine for pediatric myopia is approved in the European Union and is commercially available in parts of East Asia and India, according to Hunter. In the U.S., however, clinicians rely on compounded formulations, which are not FDA-approved and are typically paid for out of pocket. Compounded low-dose atropine varies in formulation and quality depending on the pharmacy, and a peer-reviewed study has found significant variability in concentration and stability among compounded products.
Hunter contends that beyond myopia, the rejection has raised broader concerns among industry and academic observers about regulatory predictability, particularly in pediatric drug development. Stakeholders note that pediatric trials are costly, lengthy, and difficult to execute, and that uncertainty about post-hoc changes to evidentiary expectations could discourage investment, Hunter says.
“The FDA serves a critical role in protecting public health, and rigorous standards are essential,” writes Hunter. “But when an agency provides explicit guidance, conducts ongoing reviews during clinical development, and then rejects an application that meets its own stated criteria, something has gone wrong. The FDA must establish consistent, objective standards for evaluating pediatric treatments so that future innovators aren’t left to navigate an unpredictable approval process.”
Meanwhile, a citizen petition was file 2/9 on behalf of over 1,000 U.S.-based ophthalmologists and optometrists urging FDA to (1) reconsider and expedite regulatory review of SYD-101, and (2) take appropriate regulatory action, including guidance or approval pathways, to ensure timely access to SYD-101 for U.S. pediatric patients.