Announced the first patients were enrolled in Esprit, a global Phase 2 clinical trial evaluating, an investigational drug for the treatment of late-onset Pompe disease (LOPD).
Esprit is a multicenter, randomized, placebo-controlled, double-blind study evaluating the safety, pharmacodynamics and preliminary efficacy of S-606001 as an oral substrate reduction therapy (SRT) in addition to standard of care enzyme replacement therapy (ERT) in adults with a confirmed diagnosis of LOPD.1 This 52-week study will enroll participants across the U.S., European Union and United Kingdom.1
Pompe disease is a rare genetic metabolic disorder that presents in children and adults.2,3 In people with Pompe disease, a deficiency of the acid alpha-glucosidase (GAA), an enzyme necessary for the breakdown of glycogen, results in the accumulation of glycogen in tissues throughout the body, especially in muscles.3 In LOPD, GAA activity is partially reduced.3 This can cause severe weakness and respiratory issues leading to respiratory insufficiency, wheelchair dependency and a shortened lifespan.4 LOPD affects about one in every 22,000 people worldwide and may be identified at any age.5,6 Despite significant progress in diagnosis in countries with newborn screening programs, identifying LOPD in people who are not screened at birth remains challenging.5 Its rarity, wide range of clinical presentations, and overlap with other neuromuscular disorders often lead to delays in diagnosis.7,8
S-606001 is an investigational SRT that is believed to work by limiting glycogen buildup in muscle lysosome by inhibiting glycogen synthase (GYS1).1,9 ERT, the current approved treatment for Pompe disease, infuses more GAA enzyme to increase glycogen breakdown.10 SRT blocks the GYS1 enzyme to slow down glycogen buildup.9,11 Because SRT targets the opposite side of the glycogen buildup problem from ERT, it has the potential to work alone or in combination with ERT.9,11
“The Pompe community is greatly appreciative of Shionogi’s commitment to developing new treatment options for people living with late-onset Pompe disease. Each person deserves alternatives to help them best manage their condition,” said Brad Crittenden, Chairman, International Pompe Association and Executive Director, Canadian Association of Pompe.
“Currently, ERTs are the standard of care for LOPD, but their efficacy can wane over time, leading to continued decline in skeletal muscle function. There is a significant unmet need for new treatment approaches that can be complementary to existing treatments to further slow disease progression,” said Juan Carlos Gomez, M.D., Chief Medical Officer, Shionogi & Co., Ltd. “This is an important milestone for Shionogi, as we continue to expand our work in rare disease, and we hope it will prove to be an important step forward for the Pompe community.”
Shionogi acquired exclusive worldwide rights for S-606001 (previously known as MZE001) from Maze Therapeutics, Inc. in 2024. In 2025, S-606001 received a rare pediatric disease designation from the U.S. Food and Drug Administration (FDA) for the treatment of Pompe disease, a designation granted for serious and life-threatening diseases that primarily affect children ages 18 years or younger with fewer than 200,000 people in the U.S. The FDA also granted Orphan Drug Designation to the compound in 2022.
