Sydnexis Submits IPO Filing Following FDA Rejection of Phase 3-Successful Myopia Drug SYD-101

Recently, the US FDA rejected Sydnexis, Inc.'s low-dose atropine eye drops.SYD-101The marketing application of the drug, which was originally highly anticipated for slowing myopia progression in children aged 3 to 14, and has already been approved for marketing in Europe. Despite its Phase III clinical study STARReached the pre-specified primary efficacy endpoint, FDA stillNot Approved。

Why Did the FDA Say "No"?

The reason given by the FDA in the complete response letter was very clear: although the Phase III STAR study supporting the SYD-101 application met its primary endpoint, which is the proportion of patients whose myopia progression was controlled within -0.75D met expectations,But the overall data is still insufficient to fully confirm the effect of low-dose atropine in slowing myopia in children.This statement clearly indicates that the FDA's core concern is not the safety of the drug or its manufacturing process. In fact, in the CRL, the FDA did not mention any defects related to safety or product quality, a point confirmed by Sydnexis, Inc. This means that the quality control during the drug’s manufacturing process and the assurance of safety during its use have both been recognized by the regulatory authorities. The real issue lies in the fact that, from the FDA’s professional perspective, the current evidence of efficacy presented is somewhat lacking in strength and persuasiveness.

An in-depth analysis of the FDA's considerations leads some industry experts to believe,It may have higher requirements for the comprehensiveness and long-term nature of the data.On the one hand, longer-term clinical data tracking may be needed. Myopia is a long-term developmental process, and myopia that begins in childhood may continue to affect vision health into adulthood. While current studies have observed the effects of drugs over a certain period, data on the sustained impact of these drugs on myopia progression over a longer time span may be insufficient. For example, whether the drug's efficacy fluctuates over time or if there are any long-term potential effects requires more extended research to verify. On the other hand, broader clinical data is also crucial. The mechanisms and rates of myopia development may vary among children from different regions, ethnicities, and living environments.Whether the study covered a wide enough range of children to ensure the drug demonstrates consistent efficacy in various scenarios might be where the FDA has raised questions.

Moreover, the FDA may have questions about the clinical significance of the study endpoints. Although the STAR study achieved its pre-specified primary endpoint, this endpoint, in practical clinical applications,Whether it can truly reflect the significant effect of the drug on controlling myopia in children, and whether it can effectively change the progression of myopia in children.Thereby reducing the various risks brought by myopia, such as the risk of severe complications like retinopathy and glaucoma caused by high myopia, these are issues that the FDA needs to deeply consider when evaluating drug efficacy. If the study endpoint is merely a numerical achievement and cannot establish a close connection with actual clinical benefits, then such research results will obviously be difficult to convince the FDA.

Although rejected by the FDA, SYD-101 has been approved in the EU and Japan. Santen Pharmaceutical obtained the commercialization rights for this atropine formulation (code name SYD-101) in the EU, Middle East, and Africa through a licensing agreement with Sydnexis in 2021. In June 2025, the European Commission approved Santen Pharmaceutical's low-dose atropine eye drops, Ryjunea, for marketing authorization. Previously, Santen Pharmaceutical’s 0.025% concentration of the same product series had been approved in Japan and launched in April this year under the name Ryjusea Mini, also for slowing the progression of myopia.

Multiple drugs have entered the clinical trial stage or been approved.

March 2024,Shenyang Xingqi Eye Medicine Co., Ltd. ("Xingqi Eye Medicine") has received approval for the market launch of its 0.01% Atropine Sulfate Eye Drops, which are used to slow the progression of myopia in children and adolescents.Currently, there are no similar products for myopia-related indications available on the market in China. Additionally,SydnexisAndHengrui MedicineSimilar products have been submitted for market approval.

The following are some ongoing clinical trials:

• October 2023,Vyluma Released the Results of Its CHAMP (Childhood Atropine for Myopia Progression) Phase 3 Clinical Trial,The study tested the efficacy of its low-dose atropine solution, NVK002. The New Drug Application for NVK002 is currently under review by the FDA, which has set the PDUFA target date for NVK002 as January 31, 2024.

• May 2022,ENTOD INTERNATIONAL Receives Approval from India's Drug Controller General (DCGI)Can conduct phase III clinical trials of its 0.05% atropine eye drops for treating eye problems across India.

• Sydnexis (global multicenter), Qilu Pharmaceutical, and many other pharmaceutical companies in Chinaare also conducting Phase III clinical trials.

These developments and the increase in the number of clinical trials are expected to drive the growth of the global low-concentration atropine market during the forecast period.

Join the reader communication group:

Business Cooperation:Xiaoyu Yang 15210041717