A safe and effective pharmacologic treatment for myopia has evaded researchers until a groundbreaking study was published in the early 2010’s. Commercially available atropine (1.0% and 0.5%) has been tested and been shown to be effective in treating the progression of myopia, however these high doses also have a very high incidence of adverse events that typically result in discontinuation of treatment. As a result, progressively lower doses of atropine have been tested to optimize the safety versus efficacy. Chia et al., 2012 found that 0.01% atropine given once a day retains virtually the same efficacy as 1% atropine, but with a marked reduction in side effects. This result was more widely recognized in 2017 with consensus statements by both the AAO and the WSPOS acknowledging low-dose atropine as the preferred treatment paradigm with a favorable risk-benefit ratio to minimize myopic progression. As no formulations of 0.01% atropine are approved anywhere in the world, physicians have to write off label prescriptions for compounding pharmacies to supply their patients.

Unfortunately, compounded low-dose (0.01%) atropine is pharmacologically unstable and can result in significant atropine degradation after even 1 month at room temperature (see Richdale et al., 2023). Unstable drug product poses numerous concerns for all stakeholders involved including regulatory agencies, health care professionals, and most importantly patients.
Because of this instability and the inability of most compounding pharmacies to perform testing on bottles distributed to patients, most compounded low dose atropine formulations obtained from compounding pharmacies simply state a minimum shelf life without testing (usually ~30 days) and they keep the product near physiologic pH (~pH 7) to maintain a comfortable product when applied to the surface of the eye.

Compounded products are not FDA approved and do not follow FDA guidelines. An FDA-approved product must undergo years of rigorous testing and meet very strict requirements to ensure the product is safe for use in the desired patient population. Typically, FDA approved eyedrops are stable for 18-24 months at room temperature (not 30 days!).

Trying to keep the pH of a low-dose atropine product high (~pH 7) is important for comfort, but doing so usually increases atropine degradation so companies trying to develop products for FDA testing typically lower the pH to create a more stable product. Two ‘other’ products under development have been tested at pH 3.7 and pH 4.5. But…dropping the pH of atropine may also reduce the efficacy of the product because the atropine molecule changes (gains a positive charge) as the pH drops and this change makes atropine less bioavailable.
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At Sydnexis we have solved this problem with our unique patent protected eyedrop that is currently undergoing late stage testing in the United States and Europe under the standards set for by the FDA (in the United States) and European Medicines Agency (in the European Union). Our drug product (SYD-101) is being testing in the largest progressive myopia study ever conducted and the data from this study will be available in mid-2024.