Following previous reviews during the last year (see sidebar), the US Food and Drug Administration (FDA) questioned whether results from the pivotal SYD-101-001 trial of Sydnexis' investigational atropine sulfate ophthalmic solution 0.01% demonstrate a clinically meaningful benefit, ahead of an October 30, 2026, Dermatologic and Ophthalmic Drugs Advisory Committee meeting to review its use for slowing myopia progression in children ages 3 and older. The FDA emphasized that its briefing document does not represent a final regulatory decision, and will consider the advisory committee's input before completing its review of the application. 

The 48-month, randomized, double-masked, vehicle-controlled trial enrolled 852 children ages 3 to 14 years across 47 clinical sites, including 41 in the United States. Participants had baseline myopia ranging from −0.50 D to −6.00 D and received atropine 0.01%, atropine 0.03%, or vehicle during the initial 36-month treatment period. At 36 months, 39.5% of children receiving atropine 0.01% experienced confirmed myopia progression that exceeded 0.75 D, compared with 49.3% in the vehicle group. The 9.6-percentage-point treatment difference met the prespecified statistical significance threshold (adjusted P=0.0452), but the 0.03% atropine group did not achieve statistical significance. 

The FDA reported that atropine 0.01% reduced the mean annual myopia progression rate by 0.079 D/year compared with vehicle over 3 years, corresponding to a cumulative difference of approximately 0.21 D. The agency characterized this benefit as not clinically meaningful and noted that the treatment effect diminished over time. The FDA also highlighted missing primary outcome data at month 36 for approximately 26% of participants in the 0.01% atropine group and 23% in the vehicle group. Sensitivity analyses indicated that the primary efficacy finding was vulnerable to changes in assumptions about the missing data. Additionally, the trial did not demonstrate a statistically significant reduction in axial elongation, which raised questions about the treatment's potential to modify myopia-related structural changes.

The FDA's safety review found that atropine 0.01% was generally well tolerated, with adverse event rates comparable to vehicle. Reported ocular adverse events included allergic conjunctivitis, photophobia, and instillation-site pain or irritation. No systemic anticholinergic toxicity was reported in the 0.01% treatment group. 

The advisory committee will consider whether the trial results and published research provide sufficient evidence of effectiveness or whether additional confirmatory trials are necessary.

Source: FDA Briefing Document, NDA 219694, October 30, 2026 Advisory Committee Meeting.