Eyedrops for slowing the progression of myopia: Santen files application for manufacturing and marketing approval STN1012700 / DE-127 (atropine sulfate hydrate ophthalmic solution) in Japan

February 28, 2024, Osaka, Japan - Santen Pharmaceutical Co., Ltd. (hereinafter Santen) announced today that it has filed an application for manufacturing and marketing approval in Japan for the product STN1012700 / DE-127 (generic name: atropine sulfate hydrate ophthalmic solution) (hereinafter DE-127), a product designed to slow the progress of myopia.

DE-127 is an eyedrop treatment jointly developed by Santen together with the Singapore Eye Research Institute (SERI), a national ophthalmic and visual research institute in Singapore. The product, which is designed to slow the progress of myopia, includes 0.025% atropine sulfate hydrate. Atropine is a reversible antagonist of muscarine receptors which is to inhibit muscarine receptor activity, working either directly or indirectly on the retina or sclera to prevent the thinning or stretching of the sclera, slowing the elongation of the axial length of the eye.¹ Myopia occurs when the axial length of the eye grows longer, resulting in the focusing of light rays entering the eye at a point in front of the retina. Slowing the elongation of the eye’s axial length is believed to slow or delay the progression of myopia, helping to prevent reduced Quality of Life (QOL) in myopia patients, while also contributing to the prevention of the development of serious ophthalmological complications related to myopia which can cause disorders of vision.

The effectiveness of DE-127 was investigated through a phase II/III placebo-controlled double blind comparative study conducted in Japan on children with myopia. The study, which compared the change in objectively measured spherical equivalent refraction in patients with cycloplegia [paralysis of the eye’s ciliary muscle, the muscle that controls focal accommodation] prior to drug administration and after 24 weeks of drug administration, found that patients receiving eye drops of DE-127, in comparison to the placebo eye drops, showed suppression of the change in spherical equivalent refraction, demonstrating the superiority of the treatment. In addition, measurement of the change in the axial length of the eye occurring prior to drug administration and after 24 weeks of drug administration also showed a significant difference between patients receiving eye drops of DE-127, in comparison to the placebo eye drops, demonstrating the product’s efficacy in suppressing the elongation of the axial length of the eye. These benefits were shown to be sustained over a three-year period. Further, no severe adverse events were observed in the study.

The proportion of the world’s population living with myopia, a progressive, irreversible condition, is estimated to reach 39.9% in 2030 and 49.8% in 2050.² In Japan, the School Health Statistics Survey conducted by the Ministry of Education, Culture, Sports, Science and Technology suggest that the proportion of school students with a visual acuity of below 1.0 is increasing each year, with the survey’s results showing the proportion of such students, in the Fiscal Year 2022 survey, reaching 37.88% in elementary school, 61.23% in junior high school, and 71.56% in high school.³ The rapid increase in myopia in recent years is thought to be due to lifestyle changes, namely a combination of reduced time spent outdoors and an increase in sustained focus on nearby objects as a result of reading, studying, and using digital devices.^2,4 It has been reported that progression of myopia raises the risk of future severe complications, including the possibility of severe myopia, which can cause visual disorders that lead to blindness.⁴ As the proportion of people with myopia increases dramatically, Santen and SERI worked together to develop DE-127, which aims to become the first approved product in Japan indicated for slowing the progression of myopia, addressing the need for a product that helps patients maintain and improve their QOL while reducing their risks of suffering the complications of severe myopia by expanding the range of treatment choices available for slowing the progression of myopia among elementary to junior high school age children, a time when the onset and progression of myopia is particularly prevalent.

Dr. Kyoko Ohno-Matsui, President of Japan Myopia Society, Professor of the Department of Ophthalmology and Visual Science at Tokyo Medical and Dental University, and investigator of the trial, made the following comment: “I am delighted to see the new atropine formulation, on which we have dedicated a considerable amount of time, reach a significant milestone with its submission for approval in Japan. Myopia is often not taken seriously, but it can lead to blindness if the condition progresses to pathologic myopia. Loss of eyesight from a progression of severe myopia is currently difficult to treat, and the only action available is to provide follow-ups. Given that the axial length of the eye tends to grow longer when people’s height increases—in turn causing myopia to progress—treatment during this period is critical. I hold high hopes for the potential of proposing a new treatment that focuses on slowing the progression of myopia in Japan to protect the healthy social lives of the growing number of patients.

Peter Sallstig, Chief Medical Officer at Santen made the following comment: “Myopia impacts not only important social activities such as sports and work, but since its often starting early in childhood it might continue to impact patient’s life into adulthood including the development of long-term myopic complications that may occur as it progresses. Santen, as a company committed to improving patient’s visual health, has developed DE-127 to address the medical needs presented by the rapid increase in myopia patients, and we hope that this application will lead to the provision of a new treatment option.”

Santen, which aims to help to create a society in which people around the world can experience Happiness with Vision, is actively involved in various collaborations with third-party institutions and other open innovation projects. Santen and SERI launched a long-term joint strategic research project in November 2014, with the aim of combining the respective strengths of both parties in the field of ophthalmological research and development towards the goal of developing innovative new pharmaceuticals for the treatment of frequently occurring ophthalmological conditions, particularly those conditions that affect patients in Asia. Santen and SERI continue to leverage the expertise of their respective specialists with the aim of discovering and developing new drug treatments that contribute to patient health, helping to improve the QOL of as many individual patients as possible.

About myopia
After entering the human eye, light is refracted while passing through the cornea and the crystalline lens, resulting in an upside-down image projected on the retina. Myopia denotes a vision condition where unadjusted incoming light focuses in front of the retina. This condition is thought to be mainly caused by the extension of the eyeball from the front to the rear. The degree of myopia is expressed in the spherical equivalent refractive error (unit: diopters [D]). The International Myopia Institute classifies myopia according to the value of the spherical equivalent refractive error, defining the condition of an eye with a spherical equivalent refractive error of ≤ −0.5 D as “myopia” and the condition of an eye with a spherical equivalent refractive error of ≤ −6.0 D as “high myopia.” It has been reported that high myopia patients are at high risk of complications that can lead to vision loss.⁴ Myopia is generally corrected using eyeglasses or contact lenses. However, outside Japan, various treatments are now being investigated for their potential in slowing the progression of myopia, including eyedrops, contact lenses, and orthokeratology. While some of these treatments overseas are starting to receive regulatory approval⁵, in Japan, as of January 2024, no myopia treatments had yet been approved.

References

1. Upadhyay A, Beuerman RW. Biological Mechanisms of Atropine Control of Myopia. Eye & contact lens 2020 May;46(3):129-135.
2. Holden BA, Fricke TR, Wilson DA, Jong M, Naidoo KS, Sankaridurg P, et al. Global prevalence of myopia and high myopia and temporal trends from 2000 through 2050. Ophthalmology 2016;123(5):1036-42.
3. Ministry of Education, Culture, Sports, Science and Technology: Press Release “Publication of School Health Statistics (Fixed Figures) for the 2022 School Year”. https://www.mext.go.jp/content/20231115-mxt_chousa01-000031879_1a.pdf
4. Morgan IG, Ohno-Matsui K, Saw SM. Myopia. Lancet 2012;379(9827):1739-48.
5. Japan Myopia Society: Myopia progression control treatment. https://www.myopiasociety.jp/general/care/flow.html

About Singapore Eye Research Institute
Established in 1997, Singapore Eye Research Institute (SERI) is Singapore’s national research institute for ophthalmic and vision research. SERI’s mission is to conduct high-impact eye research that prevents blindness, low vision and major eye diseases common to Singaporeans and Asians. Over the last decade, SERI has conducted landmark research projects that have led to tangible outcomes, patient benefits, and success stories. It has paved the way for significant improvements in how eye diseases are treated and prevented, not just for Singaporeans or Asians, but on a global scale.
At its inception, SERI saw a national remit in ophthalmic and vision research, and till today, SERI ensures that its facilities and resources are open to researchers across Singapore so that the greatest benefit may be obtained from what is a relatively small clinical ophthalmology catchment area in Singapore.
SERI has grown from a founding team of five in 1997 to a faculty of more than 251 staff, encompassing clinician scientists, scientists, research fellows, PhD students and support staff. This makes SERI one of the largest research institutes in Singapore, as well as the largest eye research institute in the Asia Pacific region. SERI has also over 250 adjunct faculties from various eye departments, biomedical institutes and tertiary centers in Singapore. 

SERI has published an impressive array of 5,235 scientific papers, and has secured external peer-reviewed competitive grants. As of September 2023, SERI’s faculty has been awarded with more than 1,158 national and international prizes and filed 159 patents.
As the research institute of the SNEC, and directly affiliated to the Yong Loo Lin School of Medicine, National University of Singapore, as well the Duke-NUS Medical School, SERI undertakes vision research in collaboration with local clinical ophthalmic centers and biomedical research institutions, as well as major eye centers and research institutes throughout the world.
SERI ranks first globally in terms of eye publications per capita, far ahead of the US, UK and Japan. With its impressive publication track record, SERI is comparable to renowned eye institutes, both regionally and internationally. Please see www.seri.com.sg.

About Santen
As a specialized company dedicated to eye health, Santen aspires to contribute to the realization of “Happiness with Vision” by providing products and services to patients, consumers, and medical professionals around the world. Since its establishment, and guided by its CORE PRINCIPLE, “Tenki ni sanyo suru,” Santen has been committed to helping people maintain and improve their eye health for more than 130 years. Santen is engaged in the global research and development, manufacturing, and sales and marketing of pharmaceutical products in the field of eye care, supporting the eye health of approximately 50 million people in more than 60 countries and regions worldwide. Santen’s mission is to provide essential and significant value to patients and society in the prevention, diagnosis, and treatment of eye diseases through products and services created from its expertise in the ophthalmology field and from the patient's perspective. To create a future in which as many patients as possible can lead happy and fulfilling lives, Santen is committed to doing its utmost to realize a society in which people around the world can experience “Happiness with Vision.”
For more information, please visit Santen’s website https://www.santen.com/en.

Contact
Corporate Communications
Santen Pharmaceutical Co., Ltd.
E-mail: communication@santen.com