In 2017 the World Health Organization (WHO), American Academy of Ophthalmology (AAO) and the World Society of Paediatric Ophthalmology and Strabismus (WSPOS) issued public statements identifying myopia as a massive global health problem and that myopia represents a major unmet medical need with no approved drugs to treat the disease. Since then, additional organizations have taken heed and issued statements of their own including the United Nations and the European Society of Ophthalmology. Most significantly, in 2019 the AAO created a Global Myopia Task Force partnering with the American Academy of Family Physicians (AAFP), the American Academy of Optometry (also the AAO), and the American Academy of Pediatricians (AAP). The task force released a mission statement in late 2020 stating their goal of addressing the myopia epidemic by focusing efforts on myopia early screening and treatment, as well as education. The task force highlighted low dose atropine as “the most reasonable approach to myopia control”.
Myopia the Disease
Myopia used to be considered a benign refractive disorder but is now widely recognized as a disease with significant ocular comorbidities that can occur later in life. Myopia tends to progress the most in children between the ages 5 and 15. While the precise mechanism responsible for causing myopia is unknown, the disease is believed to involve both genetic and environmental components. Near vision activities using phones, tablets, and computers have only exacerbated the incidence and progression of myopia.
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.
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.
Sydnexis has uniquely solved this problem with a novel, stable, and comfortable topical eyedrop formulation designed to be administered once daily at bedtime.
- Visit GMAC.
- Visit IMI.
- For WSPOS Consensus Statement on Myopia and a brief discussion of the use of atropine to slow the progression of myopia please click here.
- For more information on myopia, please visit the AAO website here.
- For more information on myopia treatments, click here.