Written By: Pharmacally Medical News Desk
The U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to Sydnexis Pharmaceuticals, a U.S.-based company focused on developing pediatric ophthalmic therapies, for its investigational drug SYD-101. SYD-101 is a low-dose atropine formulation designed to slow the progression of myopia in children. Although the drug met its primary endpoint in one of the pivotal STAAR Phase 3 trials, the FDA concluded that the overall evidence of effectiveness was not strong enough to support approval at this time. The program builds on earlier Asian studies that showed promising results with low concentrations of atropine for myopia control.
Detailed CRL Reason
SYD-101 was under FDA review as a potential first-in-class pharmacologic therapy for childhood myopia. The FDA’s CRL points to issues with the strength and consistency of the effectiveness data submitted for SYD-101. Despite reaching the primary endpoint, the agency expressed concerns about certain critical aspects, including:
Variability in treatment response among different patient subgroups
Uncertainty regarding the long-term durability of the therapeutic benefit
The need for additional confirmatory clinical data to solidify efficacy claims
These points collectively led to the FDA withholding approval until more comprehensive evidence is provided.
About STAAR Trial
The STAAR Phase 3 trial (Study No. NCT03918915) for SYD-101 was a randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of SYD-101 in slowing myopia progression in children aged 6 to 12 years. The trial enrolled about 600 participants across multiple centers. The primary endpoint was the change in spherical equivalent refractive error (SER) over 12 months. Results showed that SYD-101 met the primary endpoint, demonstrating a statistically significant reduction in myopia progression compared to placebo. However, the FDA raised concerns about variability in treatment response among patient subgroups and the durability of the therapeutic effect beyond one year. The agency emphasized the need for clear, consistent, and sustained evidence of efficacy before approval, leading to a request for additional confirmatory trials to address these issues.
FDA’s Stance on CRL
The FDA clarified that a Complete Response Letter reflects that the current New Drug Application cannot be approved as submitted but is not a rejection. The agency remains focused on ensuring that approved treatments provide clear, consistent, and meaningful benefits, especially for vulnerable populations like children. In a statement shared via company press release, the FDA commented, “While SYD-101 shows potential, more data are necessary to confirm its clinical value in pediatric myopia.”
Sydnexis Response
Sydnexis Pharmaceuticals has acknowledged the CRL and expressed its commitment to addressing the FDA’s concerns. The company stated in a press release, “We value the FDA’s rigorous review process and are dedicated to conducting the additional studies needed to comprehensively demonstrate SYD-101’s effectiveness.” The company is exploring plans for further clinical trials and intends to consult closely with the FDA on next steps.
Future Projection
With the CRL issuance, the regulatory approval timeline for SYD-101 will be extended. Additional clinical studies could delay market entry by several months or longer. This decision is expected to delay potential U.S. availability of SYD-101, pending additional confirmatory trials.
Key Opinions from FDA and Company
Regulatory experts highlight that this CRL underlines the FDA’s cautious approach, particularly in pediatric drug approvals. An FDA official emphasized, “Ensuring treatments for children have proven, consistent benefits is paramount.” Sydnexis’ CEO Perry Sternberg added, “We remain fully committed to advancing SYD-101 and working in partnership with the FDA to bring an effective myopia treatment to children.”
References
Sydnexis Receives Complete Response Letter from FDA for SYD-101 to Slow Pediatric Myopia Progression, 23 October 2025, Businesswire, https://www.businesswire.com/news/home/20251023759236/en/Sydnexis-Receives-Complete-Response-Letter-from-FDA-for-SYD-101-to-Slow-Pediatric-Myopia-Progression
The Safety and Efficacy of SYD-101 in Children with Myopia (STAR), ClinicalTrials.gov. Updated April 9, 2025. 2025. https://www.clinicaltrials.gov/study/NCT03918915
FDA issues Complete Response Letter to Sydnexis for SYD-101 pediatric myopia treatment, Ophthalmology Trials, 24 October 2025, https://www.ophthalmologytimes.com/view/fda-issues-complete-response-letter-to-sydnexis-for-syd-101-in-pediatric-myopia