New Phase 2 trial tests oral add-on therapy for late-onset Pompe disease
Study will evaluate S-606001 in adults already receiving enzyme therapy
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A Phase 2 clinical trial testing the experimental oral therapy S-606001 as an add-on treatment for adults with late-onset Pompe disease (LOPD) has begun enrolling patients, according to an announcement from the trial’s sponsor, Shionogi.
“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,” Juan Carlos Gomez, MD, chief medical officer at Shionogi, said in a company press release.
Study will test add-on therapy alongside standard Pompe treatment
The Phase 2 trial, dubbed Esprit (NCT07123155), aims to enroll approximately 45 adults with LOPD who are on a stable regimen of enzyme replacement therapy (ERT), the current standard treatment for this disease. Participants will be randomly assigned to receive S-606001 at one of two doses or a placebo, in addition to ERT, for 52 weeks (about a year).
The main goal of the trial is to assess whether S-606001 improves disease-related measures, including lung function such as forced vital capacity (FVC), a common test of how much air a person can forcefully exhale. Enrollment is currently underway at sites across the U.S. and Europe.
Pompe disease is caused by mutations that result in a deficiency of acid alpha-glucosidase (GAA), an enzyme needed to break down the complex sugar molecule glycogen. Without enough GAA, glycogen builds up to toxic levels in muscle cells, causing damage that leads to symptoms. ERT works by delivering a healthy version of the GAA enzyme into the body.
S-606001 is a substrate reduction therapy designed to slow glycogen production, helping limit its buildup in cells. The experimental therapy specifically targets an enzyme involved in making glycogen called GYS1 (glycogen synthase).
“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,” Gomez said.
Therapy builds on earlier research and development efforts
S-606001 was previously being developed by Maze Therapeutics under the name MZE001. A Phase 1 trial (NCT05249621) sponsored by Maze tested the therapy in healthy volunteers, with results showing it was well tolerated and reduced glycogen levels as intended.
Shionogi secured rights to the investigational therapy as part of a 2024 deal, under which Maze received an upfront payment of $150 million and is eligible for up to $255 million in clinical and regulatory milestone payments and up to $330 million in sales milestones.
“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 of the International Pompe Association and executive director of the Canadian Association of Pompe.
