Sydnexis, Inc. announced new phase 3 clinical findings from the Study of Atropine for the Reduction of Myopia Progression (STAR) trial on its low-dose atropine eye drop for the treatment of pediatric myopia.
The results were presented during last month’s American Association for Pediatric Ophthalmology and Strabismus (AAPOS) annual meeting.
First, a refresh on SYD-101.
What it is: A patented, proprietary formulation of 0.01% atropine intended to decrease myopia progression among pediatric patients.
And based on its clinical performance thus far, the drop is reported to offer:
- Enhanced ocular tissue permeability
- A stable shelf-life of up to 3 years at room temperature
- A near-neutral pH to support a favorable ocular safety and comfort profile
A regulatory note: While still investigational in the United States, SYD-101 is already approved for pediatric progressive myopia in the European Union and United Kingdom under the name Ryjunea.
What sets it apart from other myopia treatments?
That would be its unique potential to become the first and only pharmaceutical treatment option approved for progressive myopia among patients aged 3 to 14.
As a bonus: Check out how SYD-101 compares to high-dose atropine.
Now let’s talk clinical trial details.
If you’ll recall, the last we heard from Sydnexis on the randomized, double-masked, vehicle-controlled STAR study (NCT03918915) was its release of topline data in November 2025.
- And keep in mind: The trial is reportedly the “largest global clinical program completed to date in pediatric myopia.”
See here for a look at the study’s setup (evaluating two low-dose versions of SYD-101 versus a vehicle) and participant criteria (hint: over 850 patients aged 13 to 14 were enrolled).
So what did that topline data show?
Based on 3-year findings, the study met both primary and secondary outcome measures (with treatment effects observed as early as 12 months and lasting through the 36-month mark).
- Primary: Proportion of patients with a confirmed myopic progression of –0.75 D versus vehicle (139 vs 111 patients [vehicle vs 0.01%]; p=0.0226).
- Secondary: Mean myopic annual progression rate (vehicle: -0.38 D/year vs 0.01%: -0.30 D/year (p=0.0002)).
Check out the full data readout.
Alrighty, now to this latest reporting.
The focus of these findings is on SYD-101 0.01% (one of the two administered doses).
This dosage:
- Significantly reduced myopia progression across all time points tested
- Met the primary efficacy endpoint at 36 months (p = 0.0226)
- Met the key secondary endpoint of mean myopic annual progression rate (APR) at months 12, 24, and 36.
A note regarding the secondary endpoint: APR at month 36 was -0.30 D/year for SYD-101 0.01% vs -0.38 D/year for vehicle (p < 0.001)
Did this treatment benefit differ among participant age groups?
It did … the 0.01% dosage benefit was actually highest among younger myopes versus the older participants.
- In fact: 13- to 14-year-olds at treatment initiation showed minimal progression—regardless of treatment.
Give me some data.
Case in point: For myopes aged 3 to 12 at treatment initiation, myopic progression was reduced by (vs vehicle 1.07 D; 0.01% -0.77 D [p=0.0002]):
- 47.9% at 12 months
- 37.6% at 24 months
- 28% at 36 months
And of those younger patients, where were these benefits the greatest?
Among participants who exhibited fast myopic progression (>0.5 D year) as well as those with mild-to-moderate baseline myopia (-0.50 D to -3.00 D).
Can you be more specific?
Indeed, we can—the 0.01% SYD-101 dosage was found to reduce myopic progression among this patient subgroup by (versus vehicle -1.18 D; 0.01% -0.51 D [p=0.0004]):
- 76.3% at 12 months
- 65.1% at 24 months
- 56.9% at 36 months
Were there any adverse events observed?
Sydnexis reported no unexpected “atropine-related adverse events” and that SYD-101 0.01% was “well tolerated.”
Nice! So, what’s next for this drop?
If you recall (from October 2025), the FDA rejected Sydnexis’s new drug application (NDA) for SYD-101 (in which phase 3 data from the STAR trial was included).
While the agency found no issue with the drop’s safety or product quality—and acknowledged the STAR trial met its primary endpoint—it still reasoned that “the data do not support the effectiveness of low-dose atropine in children with myopia.”
… in other words?
Essentially: Despite the STAR trial meeting all its pre-established criteria for effectiveness and satisfying the FDA’s established safety requirements, the agency wanted to see even more improvement than it had initially indicated to the company.
As one report noted: “(The FDA) concluded that the data did not support effectiveness because children prescribed low-dose atropine would still have to wear glasses.”
How interesting …
Right? The company was surprised by the determination and, at the time, said it would work with the FDA to address the issues outlined in its current NDA package.
Even further: An article in the Washington Post published earlier this year (written by pediatric ophthalmologist and current AAPOS President David G. Hunter, MD), framed the FDA’s decision as a failure of regulatory consistency and judgment.
- In his writing: Dr. Hunter noted that the agency plays a vital role in safeguarding public health and must uphold rigorous standards.
- “But when an agency provides explicit guidance, conducts ongoing reviews during clinical development, and then rejects an application that meets its own stated criteria, something has gone wrong.”
To resolve this: “The FDA must establish consistent, objective standards for evaluating pediatric treatments so that future innovators aren’t left to navigate an unpredictable approval process,” he wrote.
Any other responses to this rejection?
Indeed—from several healthcare societies. Among them: the American Optometric Association (AOA),
In February 2026: The AOA issued a statement encouraging the FDA to continue evaluating the safety and efficacy of low-dose atropine for pediatric progressive myopia, noting that such an approval “would be beneficial” for eyecare providers and patients.
So where does that leave us?
With the expectation that Sydnexis plans to resubmit its SYD-101 in the near future.
As always, stay tuned for developments on this!