Shionogi & Co., Ltd. has enrolled the first patients in Esprit, a global Phase 2 clinical trial evaluating S-606001, an investigational therapy for adults with late-onset Pompe disease (LOPD). The multicenter, randomized, placebo-controlled, double-blind study will assess the safety, pharmacodynamics and preliminary efficacy of S-606001 as an oral substrate reduction therapy given in addition to standard-of-care enzyme replacement therapy in adults with a confirmed LOPD diagnosis over 52 weeks. The trial will enroll participants across the United States, European Union and United Kingdom.
Pompe disease is a rare genetic metabolic disorder that can present in both children and adults and is caused by deficiency of the acid alpha-glucosidase enzyme needed to break down glycogen. In LOPD, partial reduction of this enzyme’s activity leads to glycogen accumulation in tissues, particularly muscles, which can result in severe muscle weakness, respiratory problems, respiratory insufficiency, wheelchair dependency and reduced life expectancy. LOPD affects about one in every 22,000 people worldwide and can be identified at any age, but diagnosis remains challenging in individuals who are not identified through newborn screening due to the disease’s rarity, variable clinical presentations and overlap with other neuromuscular disorders.
S-606001 is an investigational oral substrate reduction therapy that is believed to act by limiting glycogen buildup in muscle lysosomes through inhibition of glycogen synthase (GYS1). Current approved treatment for Pompe disease relies on enzyme replacement therapy, which infuses additional acid alpha-glucosidase to increase glycogen breakdown. By blocking GYS1 and slowing glycogen production, S-606001 targets the opposite side of the glycogen accumulation pathway from enzyme replacement therapy and therefore has the potential to be used alone or in combination with existing enzyme replacement treatments.
Representatives from the Pompe patient community highlighted the need for additional therapeutic options to help individuals manage LOPD. Shionogi noted that while enzyme replacement therapies are the standard of care, their effectiveness can diminish over time, leading to ongoing decline in skeletal muscle function and underscoring the need for complementary approaches to slow disease progression. The company characterized the initiation of the Esprit trial as an important milestone in its expanding rare disease portfolio and a potential step forward for people living with Pompe disease.
Shionogi obtained exclusive worldwide rights to S-606001, previously known as MZE001, from Maze Therapeutics, Inc. in 2024. The investigational therapy received a rare pediatric disease designation from the U.S. Food and Drug Administration in 2025 for the treatment of Pompe disease, a designation reserved for serious or life-threatening conditions that primarily affect children under 18 years of age and occur in fewer than 200,000 people in the United States. The FDA also granted Orphan Drug Designation to the compound in 2022.
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