Shionogi & Co has announced a major step forward in rare disease research with the enrollment of the first patients in Esprit, a global Phase 2 clinical trial evaluating S-606001, an investigational oral therapy for late-onset Pompe disease (LOPD).

 

Esprit is a multicenter, randomized, placebo-controlled, double-blind study assessing the safety, pharmacodynamics, and preliminary efficacy of S-606001 as a substrate reduction therapy (SRT). The therapy is tested alongside standard enzyme replacement therapy (ERT) in adults with confirmed LOPD. The 52-week trial will enroll participants across the U.S., European Union, and United Kingdom.

 

Pompe disease is a rare genetic disorder caused by a deficiency in the enzyme acid alpha-glucosidase (GAA), leading to harmful glycogen buildup in tissues, particularly muscles. In LOPD, partial GAA deficiency can cause severe muscle weakness, respiratory issues, wheelchair dependency, and a shortened lifespan. The disease affects roughly one in 22,000 people worldwide and can be difficult to diagnose due to overlapping symptoms with other neuromuscular disorders.

 

S-606001 targets glycogen buildup by inhibiting the enzyme glycogen synthase (GYS1), potentially complementing ERT, which works by adding GAA to break down glycogen. “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,” Shionogi said.

 

Brad Crittenden, Chairman of the International Pompe Association, said: “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.”

 

Juan Carlos Gomez, Chief Medical Officer at Shionogi, added: “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. 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.”