Shionogi Initiates Phase 2 Trial for First Oral Substrate Reduction Therapy in Late-Onset Pompe Disease
核心洞察
Shionogi (搜索) has enrolled the first patients in Esprit, a global Phase 2 clinical trial evaluating S-606001 as the first potential oral substrate reduction therapy for late-onset Pompe disease (搜索).
The 52-week multicenter study will assess S-606001 as an add-on treatment to standard enzyme replacement therapy (搜索) in adults across the U.S., European Union, and United Kingdom.
S-606001 works by inhibiting glycogen synthase (搜索) to limit glycogen buildup, targeting the opposite mechanism from current enzyme replacement therapies that break down accumulated glycogen.
Shionogi (搜索) & Co., Ltd. announced the enrollment of first patients in Esprit, a global Phase 2 clinical trial evaluating S-606001, an investigational oral substrate reduction therapy for late-onset Pompe disease (搜索) (LOPD). The milestone represents a potential breakthrough in treating this rare genetic metabolic disorder that affects approximately one in 22,000 people worldwide.
Novel Therapeutic Approach Targets Glycogen Accumulation
The Esprit trial is a multicenter, randomized, placebo-controlled, double-blind study evaluating the safety, pharmacodynamics and preliminary efficacy of S-606001 as an add-on treatment to standard enzyme replacement therapy (搜索) (ERT) in adults with confirmed LOPD. The 52-week study will enroll participants across the United States, European Union and United Kingdom.
S-606001 represents a fundamentally different therapeutic approach compared to current treatments. The investigational drug works by limiting glycogen buildup in muscle lysosomes through inhibition of glycogen synthase (搜索) (GYS1 (搜索)). This mechanism contrasts with ERT, which infuses additional acid alpha-glucosidase (搜索) enzyme to increase glycogen breakdown.
"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," according to the study documentation.
Addressing Significant Unmet Medical Need
Late-onset Pompe disease (搜索) results from a deficiency of acid alpha-glucosidase (搜索) (GAA (搜索)), an enzyme necessary for glycogen breakdown. In LOPD patients, GAA activity is partially reduced, leading to glycogen accumulation in tissues throughout the body, particularly in muscles. This accumulation causes severe weakness and respiratory issues that can progress to respiratory insufficiency, wheelchair dependency and shortened lifespan.
"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 at Shionogi (搜索).
The diagnostic challenges surrounding LOPD compound the treatment burden. Despite progress in countries with newborn screening programs, identifying LOPD in unscreened individuals remains difficult due to the disease's rarity, wide range of clinical presentations, and overlap with other neuromuscular disorders, often leading to diagnostic delays.
Regulatory Recognition and Development Timeline
Shionogi (搜索) acquired exclusive worldwide rights for S-606001 (previously known as MZE001) from Maze Therapeutics, Inc. in 2024. The compound has received significant regulatory recognition, including a rare pediatric disease designation from the U.S. Food and Drug Administration in 2025 for Pompe disease (搜索) treatment. This designation is granted for serious and life-threatening diseases primarily affecting children 18 years or younger with fewer than 200,000 affected individuals in the United States. The FDA also granted Orphan Drug Designation to the compound in 2022.
Community Support and Future Implications
The Pompe disease (搜索) community has expressed strong support for the development program. "The Pompe community is greatly appreciative of Shionogi (搜索)'s commitment to developing new treatment options for people living with late-onset Pompe disease (搜索). Each person deserves alternatives to help them best manage their condition," said Brad Crittenden, Chairman of the International Pompe Association (搜索) and Executive Director of the Canadian Association of Pompe (搜索).
The trial represents an important milestone for Shionogi (搜索)'s expanding rare disease portfolio, which includes clinical programs for Fragile X syndrome, Jordan's Syndrome, and Pompe disease (搜索). In December 2025, the company announced plans to further expand this portfolio through acquisition of global rights to an amyotrophic lateral sclerosis treatment from Tanabe Pharma (搜索) Co., Ltd.
S-606001 remains under investigation, with safety and effectiveness not yet established by the FDA or other health authorities. Additional trial details are available at ClinicalTrials.gov under identifier NCT07123155 and at www.espritstudy.com.