FDA Panel Questions Evidence for SYD-101 Myopia Drops

An FDA advisory committee meeting ended without a vote on whether SYD-101 (atropine sulfate ophthalmic solution) should be approved to slow myopia progression in children, MedPage Today reported. The panel did not vote on whether to recommend approval, but members' responses to questions from the FDA indicated the phase III data fell short of the bar for approval.

The acting chair of the committee, Michael X. Repka, MD, of the Johns Hopkins Wilmer Eye Institute in Baltimore, told attendees that the trial was positive, but "it's not a robust outcome that would meet the standard presented to us as the reason for approval by the FDA". He added that missing data "remains sort of difficult for this committee to manage".

The application rested mainly on SYD-101-001, also called the STAR trial, which randomized 852 pediatric patients 3 years or older to 0.01% atropine sulfate ophthalmic solution, 0.03% solution, or vehicle. The main outcome was the share of patients whose myopia worsened by more than 0.75 diopters over 36 months. In the primary analysis, 39.5% of children assigned to the 0.01% dose met that endpoint, compared with 49.3% in the vehicle arm, a statistically significant difference (P=0.0452). The 0.03% arm did not separate from vehicle. That gap equaled a slowing of 0.079 diopters per year, or 0.21 diopters cumulative.

In a briefing document, FDA reviewers said the 0.01% result was statistically significant but not clinically meaningful, and the benefit shrank over time. Data for the main outcome were absent for 26% of the 0.01% group and 23% of those on vehicle, and sensitivity analyses yielded different results depending on assumptions about the missing data, they noted. The study failed to show a significant reduction in axial length, and half the sites did not measure it at all, with inconsistent techniques at those that did, according to the FDA staff report. The report added that outside randomized controlled trials in non-Asian Western populations had generally not supported the efficacy of 0.01% atropine.

The company wrote in its own DODAC report that the study had been designed with FDA input and hit its primary endpoint, with an adjusted analysis giving P=0.0226 and a key secondary endpoint at P=0.0002 for the 0.01% dose. The company noted that missing efficacy data and dropouts were similar across arms, and that every prespecified sensitivity analysis for missing data came out in favor of the 0.01% dose.

Members accepted that the main result was statistically significant but raised doubts about how robust and clinically meaningful it was. Timothy G. Murray, MD, of the University of Miami's Bascom Palmer Eye Institute, said the other studies "fall far below that standard, and therefore, I wouldn't consider that substantial evidence or a standard for approval". Biostatistician Alex Kaizer, PhD, of the University of Colorado Anschutz, said confidence intervals approached zero, making the results vulnerable to small changes, and that "more data is truly needed to understand, especially in younger ages and fast progressors, what the benefit would be".

The meeting grew out of a complete response letter the FDA sent Sydnexis in October 2025. Sydnexis said the FDA had acknowledged the primary endpoint was met but had stated its view that "the data do not support the effectiveness of low-dose atropine in children with myopia"; the letter identified no safety or product quality deficiencies. After Sydnexis filed a formal dispute resolution request, the FDA scheduled the advisory committee meeting. The agency announced no timetable for a decision at the end of the day-long session.