Sydnexis receives CRL from the FDA for its SYD-101 pediatric myopia drug

Sydnexis’ low-dose atropine formulation (SYD-101), developed to slow the progression of pediatric myopia, has received a Complete Response Letter (CRL) from the US FDA.¹

The company’s NDA for the low-dose atropine formulation was backed by data from the Phase 3 Study of Atropine for the Reduction of Myopia Progression (STAR) trial—believed to be the most extensive international clinical trial conducted on childhood myopia.^1,2 The trial involved over 800 children aged 3 to 14 at the start of treatment.^1,2 It achieved its primary efficacy goal, which measured the proportion of participants showing confirmed myopia progression of -0.75 D, a benchmark recommended by the FDA, according to the company.¹

Additionally, a key secondary outcome—the annual rate of progression—showed statistically significant improvements at 12, 24, and 36 months, the company said. In a subgroup of fast progressors (defined as more than -0.5 D per year) at 36 months, the low-dose atropine formulation demonstrated a statistically significant reduction in myopia progression exceeding 50%.¹

In its CRL, the agency recognized that the primary efficacy end point had been achieved, the company said.¹ However, the agency concluded that the evidence did not demonstrate the effectiveness of low-dose atropine for treating myopia in children.¹ The agency did not identify any deficiencies concerning safety or product quality.¹

“While we are surprised and disappointed with this decision, 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,” said Sydnexis CEO Perry Sternberg in a prepared statement.¹ “Our goal is to provide eye care professionals in the US with the first FDA-approved option to help slow the progression of pediatric myopia, rather than continued reliance on compounded formulations of atropine. 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.”

“Myopia has increased during the past few decades and is expected to continue to rise; half of the world’s population may be nearsighted by 2050,” said Michael X. Repka, MD, pediatric ophthalmologist and president of the American Academy of Ophthalmology, in an exclusive quote with the Eye Care Network. “An increase in myopia means more than just an increase in people needing to wear eyeglasses or contact lenses. People with high levels of myopia appear to be at higher risk for vision-threatening eye health complications decades later in life such as retinal detachments, myopic macular degeneration, cataracts, and glaucoma.”

“While I can’t comment on the FDA’s reasoning for denying approval, the life-long complications from high myopia are well known among the ophthalmology community and many researchers are devoted to finding safe, effective treatment options,” Repka added.

“The delay in approval is disappointing and limits myopia control options for patients and practitioners alike. It is my understanding that the clinical trial met its primary end point and thus the decision is surprising,” said Mark A. Bullimore, FCOptom, PhD, FAAO, adjunct faculty at the University of Houston College of Optometry, in an exclusive quote with the Eye Care Network.

“Around the world researchers and companies are pursuing different formulations of atropine,” Bullimore added. “More importantly, alternative pharmacological approaches are being investigated. In the meantime, this is an era in which optical myopia control options will continue to dominate, supplemented by compounded atropine.”

In June 2025, the European Commission granted marketing authorization for the company’s low-dose atropine formulation for slowing the progression of pediatric myopia, making it the first approved pharmaceutical option for managing myopia progression in EU countries.³ In April 2025, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) issued a positive recommendation for the low-dose atropine formulation intended to slow the progression of myopia in children.⁴ Under a licensing agreement, Santen SA holds the rights to market the treatment across Europe, the Middle East, and Africa, where it will be sold under the brand name Ryjunea.⁴

In March 2025, Sydnexis announced the FDA acceptance of its NDA for SYD-101, intended to treat the progression of pediatric myopia, with a PDUFA date for October 23, 2025.⁵

REFERENCES

1. Sydnexis receives Complete Response Letter from FDA for SYD-101 to slow pediatric myopia progression. News release. October 23, 2025. Accessed October 23, 2025. https://www.businesswire.com/news/home/20251023759236/en/Sydnexis-Receives-Complete-Response-Letter-from-FDA-for-SYD-101-to-Slow-Pediatric-Myopia-Progression

2. The Safety and Efficacy of SYD-101 in Children With Myopia (STAR). ClinicalTrials.gov. Updated April 9, 2025. Accessed October 23, 2025. https://www.clinicaltrials.gov/study/NCT03918915

3. Sydnexis announces European Commission approval of SYD-101, the first and only pharmaceutical treatment for slowing the progression of pediatric myopia. News release. June 5, 2025. Accessed October 23, 2025. https://www.businesswire.com/news/home/20250605515551/en/Sydnexis-Announces-European-Commission-Approval-of-SYD-101-the-First-and-Only-Pharmaceutical-Treatment-for-Slowing-the-Progression-of-Pediatric-Myopia

4. Sydnexis announces positive CHMP opinion in Europe for SYD-101 for slowing the progression of pediatric myopia. News release. April 1, 2025. Accessed October 23, 2025. https://sydnexis.com/2025/04/01/sydnexis-announces-positive-chmp-opinion-in-europe-for-syd-101-for-slowing-the-progression-of-pediatric-myopia/

5. Sydnexis announces FDA acceptance of new drug application and PDUFA date for SYD-101, for the treatment of progression of pediatric myopia. News release. March 11, 2025. Accessed October 23, 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/