SYDNEXIS Inc.: atropine sulfate

There is a lack of substantial evidence consisting of adequate and well-controlled investigations, as defined in 21 CFR 314.126, that the drug product will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in its proposed labeling.

Specifically, the clinical study contained and the referenced literature in this submission do not support the effectiveness of atropine sulfate ophthalmic solution, 0.01% for the treatment of myopia in children.

In Study SYD-101-001, the atropine 0.01% dose but not the atropine 0.03% dose met the primary endpoint.

This small difference in spherical equivalent is not clinically meaningful and would not result in a change in glasses prescription.

The small and diminishing magnitude of the reduction in myopia seen in this trial would be unlikely to reduce the future risk of retinal complications in any meaningful way, given that there was no difference in the change from baseline in axial length between the treatment and placebo group.

Placebo-Controlled Trial of 0.05%, 0.025%, and 0.01% Atropine Eye Drops in Myopia Control.

Placebo on Myopia Incidence in Children: The LAMP2 Randomized Clinical Trial.

While Study SYD-101-001 achieved its prespecified primary endpoint, multiple factors raise significant concerns regarding the robustness and clinical meaningfulness of the observed treatment effect:

0.01% vs. Vehicle) at -1.28%, indicating limited clinical benefit.

Sensitivity analyses revealed the primary result lacks robustness.

Low-Dose 0.01% Atropine Eye Drops vs Placebo for Myopia Control: A Randomized Clinical Trial.

These findings collectively suggest limited to no clinical benefit with questionable durability and robustness of the treatment effect.