Santen Obtains Manufacturing and Marketing Approval in Japan for UPNEEQ^® Mini Ophthalmic Solution 0.1%, a Treatment for Acquired Blepharoptosis

December 22, 2025 – Osaka, Japan – Santen Pharmaceutical Co., Ltd. (hereinafter Santen) announced today that it has obtained manufacturing and marketing approval in Japan for UPNEEQ^® Mini Ophthalmic Solution 0.1% (generic name: oxymetazoline hydrochloride; development code: STN1013800; hereinafter the product), a treatment for acquired blepharoptosis.

Blepharoptosis is classified into congenital and acquired forms and acquired blepharoptosis has a variety of causes. Many cases are aponeurotic, resulting from degenerative changes in the levator aponeurosis, with long-term contact lens wear reported as a risk factor.^1-4 This condition causes the upper eyelid to droop and gives rise to a variety of symptoms, including loss of the upper visual field, stiff shoulders, headaches, and fatigue,⁵ as well as changes in the appearance of the eyes. At present, treatment for blepharoptosis is primarily limited to surgical procedures. The product is the first approved non-invasive treatment in Japan for acquired blepharoptosis, offering a potential alternative to surgery by elevating the upper eyelid and improving the associated symptoms.

Oxymetazoline, the active ingredient of the product, has been reported to act as an agonist for the α₁- and α₂-adrenergic receptors.⁶ By acting on α receptors in Müller’s muscle, which contributes to eyelid elevation, the product induces muscle contraction and lifts the upper eyelid.⁷

In a Phase 3, placebo-controlled, randomized, double-masked study conducted in Japan, the efficacy and safety of once-daily administration of the product were evaluated in patients with acquired blepharoptosis. The superiority of the product was demonstrated in the primary endpoint — a change from baseline at 2 hours after administration in MRD-1 (Marginal Reflex Distance-1, the margin between the upper eyelid and the center of the pupil)* at Day 14 after the start of treatment—in the once-daily group versus the placebo eye drop group. In addition, an exploratory analysis showed that improvement in MRD-1 persisted for more than 8 hours after instillation. Regarding safety, eyelid pruritus (1 case out of 112) was observed in the drug administration group, but no serious adverse effects or adverse effects leading to treatment discontinuation were reported.

Santen’s Chief Medical Officer, Peter Sallstig commented: “Blepharoptosis is a condition that not only causes noticeable changes in appearance but also narrows the visual field, leading to a decreased quality of life for patients. Outside of the United States, surgery is currently the only approved treatment for blepharoptosis. Santen is committed to advancing research and development in ophthalmology areas where no eye drop therapies are currently available. This product is one such example. As a global pharmaceutical company specialized in ophthalmology, we will continue to address the diverse needs of patients.”

With this product—the first approved non-surgical treatment for acquired blepharoptosis in Japan—Santen will continue to address the needs of patients in Japan while continuing its efforts to provide new treatment options to patients with blepharoptosis worldwide.

References

1. Custer PL, et al. Ophthalmology. 3rd ed. 2008;1397-1403.
2. Van den Bosch WA, et al. Ophthalmology. 1992;99(12):1759-65.
3. Kersten, RC, et al. Ophthalmology. 1995;102(6):924-8.
4. Reddy AK, et al. Ophthalmology. 2007;114(12):2370.
5. Battu VK, et al. Am J Ophthalmol. 1996;121(6):677-686.
6. Haenisch B, et al. Fundam Clin Pharmacol. 2010;24(6):729-39.
7. Slonim CB, et. al. JAMA Ophthalmol. 2020;138(11):1168-75.

• In this clinical study, MRD-1 was defined as the distance from the center of the pupil to the upper eyelid margin, as determined from anterior segment photographs.

About UPNEEQ^® Mini Ophthalmic Solution 0.1%
In July 2020, Santen entered into an exclusive license agreement with Osmotica Pharmaceuticals plc (due to a company name change, now known as RVL Pharmaceuticals, Inc), covering the continued development, registration, and commercialization rights for RVL-1201, a 0.1% oxymetazoline hydrochloride ophthalmic solution, in Japan, China, other Asian countries, and EMEA (Europe, Middle East and Africa). Santen has been developing the product as STN1013800.
In the United States, RVL Pharmaceuticals, Inc has obtained approval from the U.S. Food and Drug Administration (FDA) for UPNEEQ^® (oxymetazoline hydrochloride ophthalmic solution 0.1%) for the treatment of acquired blepharoptosis in adults, and the product is marketed as the first and only FDA-approved treatment for acquired blepharoptosis in adults in the United States.

About Santen
Santen is a global pharmaceutical company committed to advancing eye health and improving lives through better vision. Founded in 1890 in Osaka, Japan, Santen makes use of more than 135 years of experience in research and development, manufacturing, and marketing of pharmaceuticals and medical devices to help people around the globe maintain and improve their eye health. Santen focuses exclusively on eye health and its portfolio includes glaucoma, dry eye, infection, allergy, age-related macular degeneration, and myopia. Santen’s products and services are available in more than 60 countries and regions. Guided by its Core Principle “Tenki ni sanyo suru” – Exploring the secrets and mechanisms of nature in order to contribute to people’s health – Santen combines its expertise with deep patient focus to contribute to the realization of “Happiness with Vision.”
For more information, please visit https://www.santen.com/en.

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