Acucela Inc. a clinical-stage ophthalmology company and wholly-owned subsidiary of Kubota Pharmaceutical Holdings Co., Ltd. specialising in identifying and developing novel therapeutics to treat and slow the progression of sight-threatening ophthalmic diseases, have announced that the FDA (U.S. Food and Drug Administration) has granted orphan drug designation to Acucela’s leading drug candidate emixustat hydrochloride (“emixustat”) for the treatment of Stargardt disease.
The Orphan Drug Act (ODA) provides for granting special status to drugs and biologics intended for the safe and effective treatment, diagnosis or prevention of rare diseases and disorders that affect fewer than 200,000 people in the U.S.
Stargardt disease is a rare, genetically inherited disease that directly affects the retina of the eye, often resulting in the slow progression of vision loss in children. It may also be referred to as Stargardt macular dystrophy or juvenile macular degeneration and affects approximately 1 in 10,000 individuals worldwide. The most common form of the disease is caused by a genetic mutation of the ABCA4 gene leading to the accumulation of toxic vitamin A by-products (primarily A2E) in the retina, which results in the gradual deterioration of photoreceptors and vision. Symptoms of Stargardt disease typically appear during childhood or adolescence, but in some cases difficulty with eyesight and vision loss may not be identified until later in life.
Currently, there are no known therapies that exist to slow the advance of the disease, and it is recognised as a serious unmet medical need by the United States Foundation of Fighting Blindness and the National Eye Institute.
The visual cycle is the process by which vitamin A is recycled in the eye; vitamin A is crucial to the visual process. Emixustat modulates the visual cycle by inhibiting a critical enzyme of this pathway, retinal pigment epithelium protein 65 (RPE65). Slowing the visual cycle reduces the availability of vitamin A derivatives (11-cis- and all-trans-retinal) to form precursors of A2E and related compounds. In animal models of Stargardt disease and retinal degeneration, emixustat was found to stop and reverse the accumulation of A2E and to preserve the integrity of the retina. Emixustat when delivered orally was found to be generally well tolerated in human clinical studies with delayed dark adaptation being the most common ocular adverse event. Acucela is planning to explore emixustat’s potential to stop or slow the progression of vision loss in patients diagnosed with Stargardt disease in future clinical studies.