FDA forms advisory committee to review Sydnexis's low-dose atropine

The FDA is convening an advisory meeting to review and discuss Sydnexis, Inc’s SYD-101, an investigational formulation of low-dose atropine intended for the treatment of pediatric progressive myopia (PPM).

This latest update follows nearly 9 months after the federal agency rejected the eye drop’s new drug application (NDA).

Sounds like we’ve got some catching up to do …

Indeed. First, though, a rundown on SYD-101 is in order:

What it is: A patented, proprietary 0.01% atropine formulation intended to slow myopia progression in pediatric patients.

Among its unique properties: As Sydnexis has noted, the drop is designed to “optimize tolerability, stability, and clinical performance” via several mechanisms:

Enhanced ocular tissue permeability (as demonstrated in preclinical animal studies)
Stable shelf-life for up to 3 years at room temperature
Near-neutral pH (potentially supporting its favorable ocular safety and comfort profile)

And its potential?

SYD-101 has the potential to become the first and only pharmaceutical treatment approved for progressive myopia in patients aged 3 to 14.

Bonus read: See how SYD-101 stacks up against high-dose atropine.
Also keep in mind: It’s already approved for PPM as Ryjunea (licensed under Santen S.A.) in the European Union and United Kingdom.

So how did it perform in clinical trials?

The eye drop’s clinical performance in the phase 3 Study of Atropine for the Reduction of Myopia Progression (STAR) study (NCT03918915) was reported pre-NDA and post-NDA submission.

Notably: Sydenixis has referred to this phase 3 trial as the “largest global clinical program to date in pediatric myopia.”

Talk about these data readouts.

Positive 3-year findings were included in Sydnexis’s NDA submission to the FDA, in which the study met both its primary and secondary endpoints:

Primary: Proportion of patients with confirmed myopic progression of -0.75D
Secondary: Annual progression rate met statistical significance at 12, 24, and 36 months

Check out the full topline data, which was released just days after the FDA rejected SYD-101’s package.

And in the second round of data?

The most recent findings from the STAR study were reported this past April during the American Association for Pediatric Ophthalmology and Strabismus (AAPOS) annual meeting.

As we previously covered, these outcomes were based on the 0.01% dose (one of two administered during the study) of SYD-101, in which the 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.

Get the full recap (with numbers) here.

Now, remind me: Why did the FDA reject its NDA?

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 (as we previously reported): Despite the STAR trial meeting all its pre-established criteria for effectiveness and satisfying the FDA’s established safety requirements, the agency essentially wanted to see even more improvement than it had initially indicated to the company.

In response to this, Sydenixis submitted a formal dispute resolution request (FDRR)
Click here to see how several healthcare societies (including the American Optometric Association) weighed in on this move.

That brings us to this FDA advisory committee.

Indeed. The federal agency has informed Sydnexis of plans to “convene an advisory committee” that will discuss SYD-101 for the treatment of PPM.

The timeframe for the meeting: Still to be determined.

However: Sydnexis said the FDA “indicated that the Advisory Committee will be asked to discuss various aspects of the company’s application”—including data from the STAR trial.

Do we know who will attend the meeting?

Per Sydnexis CEO Perry Sternberg, the company has asked for the FDA to include practicing pediatric ophthalmologists and optometrists. “They understand the long-term challenges facing patients and families every day,” he stated.

“We believe this meeting provides an important opportunity to have a robust, science-led discussion around the totality of evidence supporting SYD-101 and we look forward to hearing the perspectives of clinicians who treat PPM on a daily basis,” Sternberg added.

Let’s talk about this from a big-picture perspective.

Low-dose atropine and PPM often go hand-in-hand—even though there’s currently no FDA-approved pharmaceutical available as a treatment option.

As such: Compounded low-dose atropine is commonly prescribed to slow myopia progression among pediatric patients.

The issue with this: Compounded products do not undergo the standard FDA review process for safety, effectiveness, manufacturing consistency, and labelling—nor post-marketing surveillance requirements—as an approved prescription therapy.

Compounding pharmacies also typically operate under state board of pharmacy, translating to varying levels of compliance within USP guidelines.
And from an access perspective: These are also often not covered by insurance.

… and this begs the need for an FDA-approved option?

Correct. In fact, such a need has also been supported by national organizations, like the American Academy of Ophthalmology (AAO) and the AAPOS.

See here for the AAO’s report in favor of low-dose atropine for myopia.

And more recently (as in earlier this month): Check out the AAPOS Myopia Task Force’s statement welcoming the FDA’s decision to further evaluate low-dose atropine for PPM.

“We support a rigorous, science-based review process that includes fair-minded clinicians with substantial experience currently treating children with progressive myopia using contemporary myopia-control therapies,” the task force wrote.

Go on …

Also worth noting: Earlier this year, a physician-directed public petition signed by over 1,000 U.S. eyecare providers (ECPs) called for the FDA to reconsider its rejection of Sydnexis’s drop, emphasizing that “early intervention with SYD-101 may reduce the long-term burden of avoidable retinal disease and vision loss.”

And as the authors wrote in their submission to the FDA:

“This level of support reflects broad national clinical consensus regarding the safety, efficacy, and public-health importance of making SYD-101 available to U.S. children.”

Noted. So … do we know when this committee will meet?

Unfortunately, no. In announcing this committee formation, Sydnexis provided no timeframe for the meeting itself or when we might hear the outcomes.

So you know what that means: Stay tuned!