FDA Cites Insufficient Data for SYD-101, Potential Therapy to Slow Pediatric Myopia Progression

The FDA issued a complete response letter (CRL) to Sydnexis on Thursday, stating that its cited clinical trial data did not support the efficacy of SYD-101, a low-dose atropine formulation to treat and slow the progression of myopia in pediatric patients.^1,2

SYD-101 was poised to become the first pharmaceutical option in the US specifically for pediatric myopia, which is on the rise generally, with about 28 million children affected in the US alone. These children are at a higher risk of developing other ophthalmological complications over time, including retinal detachment, glaucoma, cataracts, and myopic maculopathy.

Although optical interventions (such as specialized contact lenses or spectacle designs) are available, there is no FDA-approved pharmacologic therapy currently available in the US to slow myopia progression. The FDA accepted the new drug application in March of this year, and the European Commission authorized SYD-101 in June.^3,4

The FDA acknowledged in its letter that the primary end points of the Safety and Efficacy of SYD-101 in Children with Myopia trial (STAR; NCT03918915) were met, but said it was not enough to prove that low-dose atropine would prevent the progression of myopia in pediatric patients.¹

The letter did not list any specific deficiencies in safety or product quality; however, atropine is widely acknowledged to have an unstable shelf life. Other atropine products have struggled with issues such as batch-to-batch variability and degradation over time.^1,5-6

Perry Sternberg, CEO of Sydnexis, said in a news release that "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. ... We remain confident in our data and the potential of SYD-101 to fill a critical innovation gap and treat the most common eye disease in children.”

What Are the Supporting Clinical Data?

STAR was a phase 3, multicenter, randomized, double-masked, vehicle-controlled trial that enrolled approximately 850 children aged 3 to 14 years, with multiple dose arms (eg, 0.01% and 0.03%) and a placebo arm in Sydnexis, called the largest clinical study ever for pediatric myopia progression.^2,7

Over 3 years, the trial assessed progression of myopia (measured in diopters) as its primary end point, along with safety, tolerability, and secondary end points including axial elongation and related ocular comorbidities. After the third year, participants enter a randomized withdrawal (washout) phase for exploratory analyses. Although detailed results have not yet been fully published, STAR reportedly met its 3-year primary end point, supporting statistically significant slowing of myopic progression.⁴

Sydnexis developed SYD-101 as a proprietary, low-dose atropine ophthalmic drop formulation designed to deliver consistent pharmacologic effect with improved shelf stability, comfort, and tolerability compared with other, higher-dose atropine solutions.⁵

In a 2023 Q&A by Review of Myopia Management Chief Medical Editor Dwight Akerman, OD, MBA, FAAO, FBCLA, FIACLE, Gregory Ostrow, MD and Patrick Johnson, PhD, both of Sydnexis, described atropine’s chemical instability, batch-to-batch variability, and the challenges in creating a formulation that was safe enough for pediatric patients. They said SYD-101 uses a stabilizing agent to mitigate degradation and improve consistency and tolerability.⁶

REFERENCES

1. Sydnexis receives complete response letter from FDA for SYD-101 to slow pediatric myopia progression. News release. Sydnexis. October 23, 2025. Accessed October 24, 2025.

2. Sydnexis announces FDA acceptance of new drug application and PDUFA date for SYD-101, for the treatment of progression of pediatric myopia. News release. Sydnexis. March 11, 2025. Accessed October 17, 2025. https://sydnexis.com/2025/03/11/sydnexis-announces-fda-acceptance-of-new-drug-application-and-pdufa-date-for-syd-101-for-the-treatment-of-progression-of-pediatric-myopia

3. Ebert M. FDA accepts NDA for SYD-101 to treat pediatric myopia. Contemporary Pediatrics. March 11, 2025. Accessed October 17, 2025. https://www.contemporarypediatrics.com/view/fda-accepts-nda-for-syd-101-to-treat-pediatric-myopia

4. Sydnexis announces European Commission approval of SYD-101, the first and only pharmaceutical treatment for slowing the progression of pediatric myopia. News release. Sydnexis. June 5, 2025. Accessed October 17, 2025. https://www.biospace.com/press-releases/sydnexis-announces-european-commission-approval-of-syd-101-the-first-and-only-pharmaceutical-treatment-for-slowing-the-progression-of-pediatric-myopia

5. Karpecki PM, Kaiser Maharjan E. Inside the MOA of SYD-101, the potential first FDA-approved formulation of low-dose atropine. Optometry Times. March 27, 2025. Accessed October 17, 2025. https://www.optometrytimes.com/view/inside-the-moa-of-syd-101-the-potential-first-fda-approved-formulation-of-low-dose-atropine

6. Sydnexis Featured in Review of Myopia Management. Sydnexis. August 15, 2023. Accessed October 17, 2025. https://sydnexis.com/2023/08/15/sydnexis-featured-in-review-of-myopia-management

7. The safety and efficacy of SYD-101 in children with myopia (STAR). ClinicalTrials.gov. Updated April 9, 2025. Accessed October 17, 2025. https://clinicaltrials.gov/study/NCT03918915