Sydnexis, Inc. announced new topline phase 3 data on SYD-101, a low-dose atropine eye drop, for the treatment of pediatric myopia.
This reporting follows just one week after the FDA’s rejection of its new drug application (NDA).
Lots of recent developments … but let’s start with SYD-101.
As we’ve already covered this eye drop extensively, we’ll give just the basics:
- What it is: A proprietary formulation of 0.01% atropine engineered specifically for younger patients.
- What it offers: Enhanced ocular tissue permeability and a stable shelf-life of up to 3 years at room temperature
- Its uniqueness: SYD-101 has the potential (despite this regulatory setback) to become the first and only pharmaceutical treatment option approved for progressive myopia for patients aged 3 to 14.
See here for more insights into this low-dose (versus high-dose) treatment.
And that recent federal rejection?
Let’s back up for a second: The FDA originally accepted Sydnexis’s NDA submission in March 2025.
But fast forward to last week: The agency sent the company a company response letter (CRL) that essentially took issue with the clinical data accompanying the application.
- Specifically: A lack of data supporting the drop’s effectiveness in treating myopia.
- Check out our full coverage on this.
So where does this new data fit in?
The latest topline findings are from the phase 3 Study of Atropine for the Reduction of Myopia Progression (STAR) study (NCT03918915).
- And before you ask: Yes, this study was included in that aforementioned NDA submission.
So what should we know about STAR?
The randomized, double-masked, vehicle-controlled trial evaluated SYD-101 in two doses (0.01% and 0.03%) versus a placebo among over 850 pediatric (aged 3 to 14) patients.
- Get a complete rundown on the study’s setup, participant criteria, and primary/secondary endpoints.
Its claim to fame: The company has referred to STAR as “the largest global clinical program completed to date in pediatric myopia.”
Were there any prior findings to be aware of before this?
None that were reportable. Upon that NDA submission, the study had recently completed its third year, participants are being re-randomized into a 1-year washout.
Got it. Now to this 3-year data.
First: The study met both outcome measures at 36 months in the full study population:
- 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).
- Notably, this was proposed by the FDA
- Secondary: Mean myopic annual progression rate (vehicle: -0.38 D/year vs 0.01% -0.30 D/year (p=0.0002).
Notably: Treatment effects were evident starting at Month 12 and sustaining through to Month 36.
Sounds promising …
Indeed. However, Sydnexis noted that this success was despite “36% of the total patients in the SYD-101 0.01% arm” being between ages 16 and 18 as well as exhibiting “very little progression by the end of the study.”
And how did both SYD-101 doses compare to vehicle?
Based on a “pre-specified analysis” of the change from baseline spherical equivalent (SE), SYD-101 demonstrated “significantly smaller changes” versus vehicle in the full study population.
The numbers:
- Vehicle ‑0.92 D
- SYD-101 0.01%: -0.71 D (p-0.0022)
- SYD-101 0.03%: 0.76 D (p=0.0158)
And in general: Participants receiving 0.01% and 0.03% took significantly longer to reach myopic progression worse than –0.75 D at Month 36 (p = 0.0071 and p = 0.0080, respectively), according to the study data.
Did this change based on patients’ ages?
The “magnitude of clinical effect of change in SE” was found to be “even larger” among younger patients (ages 3 to 12 upon treatment initiation).
Both SYD-101 doses reportedly demonstrated “nominal statistical significance.”
- SYD-101 0.01%: –0.77 D (p=0.0002)
- SYD-101 0.03%: 0.85 D (p=0.0065)
- Vehicle: –1.07 D
Were there any fast myopic progressors in the population?
Indeed there were. Specifically, a subgroup with more than –0.5 D/year progression (prior to the study, of course).
For these patients with low-to-moderate myopia (–0.5 D to –3.00 D) at the start of the study, myopic progression was reduced by the following at the 36-month mark:
- SYD-101 0.01%: –0.51 D (p=0.0004)
- SYD-101 0.03%: –0.92 D (p = 0.1505)
- Vehicle: –1.18 D
How about potential adverse effects?
In general, SYD-101 was “well tolerated” and resulted in no unexpected atropine-related adverse events (AEs).
So, in a nutshell?
A few takeaways to keep in mind:
- The greatest treatment benefit was noted when SYD-101 was administered earlier in myopic progression (in younger pediatric patients) as well as in those with a history of myopia progression.
- This data emphasizes the critical need for early disease-modifying intervention in pediatric myopia.
To note: The phase 3 findings were presented in a poster session at Academy of Managed Care Pharmacy (AMCP) Nexus 2025 in National Harbor, Maryland. For a deeper dive into the findings, click here.
And what does this mean for SYD-101’s NDA?
Unclear at the moment, as Sydenxis didn’t offer any update on its application when reporting the topline data (just that they’re working with the FDA to address the NDA’s issues).
- However: CEO Perry Sternberg previously shared that the company remains “confident” in their data and SYD-101’s potential to “fill a critical innovation gap and treat the most common eye disease in children.”
And keep in mind: The company can most definitely resubmit an updated NDA in the near future.