SYD-101's CRL: A shifting of FDA goalposts

On October 23, 2025, the FDA issued a complete response letter (CRL) to Sydnexis regarding its new drug application (NDA) for SYD-101, a 0.01% atropine eye drop intended to slow pediatric myopia progression. Although acknowledging that the STAR trial met its primary end point, the FDA concluded that the data did not sufficiently demonstrate clinical meaningfulness. The decision is unprecedented, as end points are agreed upon by the FDA prior to a company commencing its pivotal clinical trial, which can cost tens of millions of dollars. Meet the end points, anticipate approval.

Subsequently, over 1000 doctors were moved to sign an online petition, urging “the FDA to move forward in making a safe, consistent, well-regulated low-dose atropine therapy available to the millions of US children facing progressive myopia.”¹ I have consulted for Sydnexis along with many other companies, including CooperVision and EssilorLuxottica, prior to their respective FDA approvals. Thus, I have a nuanced view of the situation. My rationale for supporting FDA approval of low-concentration atropine is as follows.

First, I believe we should all be on “Team Myopia.” FDA approval of atropine would help all physicians deliver the best possible care to their patients. Atropine can then be prescribed, either as a monotherapy or to enhance the efficacy of optical myopia control therapies.²

Second, the approval of a formulation controlled by the FDA would be a significant move forward and give practitioners another safe option. Clinicians currently rely on using loosely regulated compounding pharmacies to supply their patients with atropine. This approach shows unacceptable variability.³ If you want to learn more about this sector of the industry, you should look no further than John Oliver’s hilarious late-night takedown.⁴

Third, if you look at some of the supplementary materials on the Sydnexis website, you would see that in groups of children who would typically be prescribed low-dose atropine, the efficacy is substantially higher than in the overall clinical trial population.⁵ The company was somewhat hamstrung by requirements that they recruit older children. These children typically experience progression at slower rates. Considering children younger than 9 years, the 3-year efficacy of 0.01% atropine is 0.51 D. Likewise, in children with low myopia and documented progression prior to study entry, the efficacy approaches 0.70 D. Some of these FDA-predefined subgroup analyses appear in the recently published report of the 2-year data.⁶

Finally, it is important to note that Sydnexis met its primary study end point. Some might regard it as a dangerous precedent that the FDA did not then approve the application. This decision has the potential to stifle innovation and deter companies from investing huge sums of money to conduct these clinical trials if a government agency then moves the goalposts. In this regard, the FDA’s decision has resulted in broader engagement, including an editorial in The Washington Post by David Hunter, MD, president of the American Association for Pediatric Ophthalmology and Strabismus,⁷ and statements from a number of professional organizations.^8-10

In the meantime, the process is ongoing. Sydnexis is appealing the decision through the FDA’s administrative process. So although Sydnexis’ atropine formulation has been approved by the European Medicines Agency, based on shorter-term data than those submitted to the FDA, US-based clinicians and patients are in a holding pattern. I’m hopeful for an ultimate approval, which would represent a win for all stakeholders, including the FDA.

Disclosure statement

Mark Bullimore, PhD, MCOptom, is a consultant for Alcon, Bruno Vision, CooperVision, Dopavision, EssilorLuxottica, Euclid Vision, Johnson & Johnson, Kubota Vision, Laboratoires Théa, Santen Pharmaceutical, SightGlass Vision, Sydnexis, Visioneering Technologies, and Xingqi Pharmaceutical.

References

1. Urgent call for U.​S. children to have access to an FDA-approved low-dose atropine. Change.org. Accessed April 27, 2026. https://www.change.org/p/urgent-call-for-u-s-children-to-have-access-to-an-fda-approved-low-dose-atropine-68d0a62c-8058-48bb-ab09-9c586d3a3ff6

2. Thakur S, Han T, Bullimore MA, Chen Z, Verkicharla PK. Current evidence on options and efficacy of combination therapy for myopia control-a narrative review. Ophthalmic Physiol Opt. Published online April 13, 2026. doi:10.1007/s44402-026-00071-x

3. Richdale K, Skidmore KV, Tomiyama ES, Bullimore MA. Compounded 0.01% atropine-what's in the bottle? Eye Contact Lens. 2023;49(6):219-223. doi:10.1097/ICL.0000000000000990

4. Compounding pharmacies: Last Week Tonight with John Oliver (HBO). YouTube. September 30, 2019. Accessed April 27, 2026. https://www.youtube.com/watch?v=Nuzi7LlSDVo

5. Cheetham JK, Gieschen L, Kirkeby L, Widder K, Johnson P. Evidence from the STAR study: a novel low-dose atropine eye drop slows the progression of pediatric myopia. Sydnexis. November 3, 2025. Accessed April 27, 2026. https://sydnexis.com/resource/evidence-from-the-star-study-a-novel-low-dose-atropine-eye-drop-slows-the-progression-of-pediatric-myopia/

6. Korenfeld M, Hurcikova M, Tatsuoka K, Tomciková D, Cheetham J, Kacerik M; STAR Study Investigators. Study of atropine to reduce (STAR) myopia progression in children: twenty-four-month results of a randomized, double-masked, vehicle-controlled trial of atropine sulfate 0.01% and 0.03. Ophthalmol Ther. Published online March 23, 2026. doi:10.1007/s40123-026-01341-0

7. Hunter DG. This drug treats myopia: I'm sick of telling patients they can't have it. Washington Post. February 10, 2026. Accessed April 27, 2026. https://www.washingtonpost.com/opinions/2026/02/10/fda-myopia-drug-trial/

8. Low dose atropine (LDA) bulletin 2025. World Society of Paediatric Ophthalmology and Strabismus. Accessed April 27, 2026. https://wspos.org/wp-content/uploads/2025/12/LDA-Bulletin-11th-Dec-2025.pdf

9. AAPOS Myopia Task Force statement on the FDA’s decision regarding SYD-101 for the treatment of progressive childhood myopia. LinkedIn. Accessed April 27, 2026. https://www.linkedin.com/posts/aapos_myopia-task-force-statement-fdas-syd-101-activity-7398842860198060032-rOnz/

10. AOA statement to FDA on low-dose atropine. American Optometric Association. February 5, 2026. Accessed April 27, 2026. https://www.aoa.org/about-the-aoa/press-room/statements/aoa-statement-to-fda-on-low-dose-atropine