The U.S. Food and Drug Administration (FDA) has approved Nexviazyme (avalglucosidase alfa-ngpt) for the treatment of patients one year of age and older with late-onset Pompe disease, a progressive and debilitating muscle disorder that impairs a person’s ability to move and breathe. Nexviazyme is an enzyme replacement therapy (ERT) designed to specifically target the mannose-6-phosphate (M6P) receptor, the key pathway for cellular uptake of enzyme replacement therapy in Pompe disease. Nexviazyme has been shown in clinical trials to provide patients with improvements in respiratory function and walking distance.

“Pompe disease is a debilitating and progressive condition that significantly inhibits mobility and breathing,” said Bill Sibold, Executive Vice President of Sanofi Genzyme. “For decades, we’ve made it our responsibility to research how to target the M6P receptor, the key pathway for cellular uptake of enzyme replacement therapy. Nexviazyme is a potential new standard of care for people living with late-onset Pompe disease and delivers on our promise to pursue medicines for patients living with rare diseases.”

Pompe disease affects an estimated 3,500 people in the United States and can present as infantile-onset Pompe disease (IOPD), the most severe form of Pompe disease with rapid onset in infancy, and late-onset Pompe disease (LOPD), which progressively damages muscles over time. LOPD symptoms may present at any age. However, due to the wide spectrum of clinical presentations and progressive nature of the disease, it can take seven to nine years before patients receive an accurate diagnosis. As the disease progresses, people with LOPD may require mechanical ventilation to help with breathing or a wheelchair to assist with mobility.

Targeted delivery to clear glycogen in muscle cells

Pompe disease is caused by a genetic deficiency or dysfunction of the lysosomal enzyme acid alpha-glucosidase (GAA), which results in the build-up of complex sugars (glycogen) in muscle cells throughout the body. The accumulation of glycogen leads to irreversible damage to the muscles, including the diaphragm that supports respiratory function and skeletal muscles that affect mobility, functional endurance and breathing.
        
The key pathway to transport GAA enzyme into the lysosomes in the cell is through the M6P receptor. Nexviazyme is specifically designed to target M6P to improve cellular enzyme uptake and enhance glycogen clearance in target tissues with an approximately 15-fold increase in M6P content compared to alglucosidase alfa, the comparator arm in the pivotal study.

Nexviazyme has demonstrated improvements for people living with late-onset Pompe disease. In the pivotal Phase 3 trial (COMET), Nexviazyme showed improvements in respiratory function and walking distance measures in people with LOPD and established its safety profile.

“Nexviazyme is a new and exciting therapeutic option for people with late-onset Pompe disease,” said Mazen M. Dimachkie, MD, FAAN, FANA, Professor of Neurology, Chief of the Neuromuscular Division and Executive Vice-Chair of the Department of Neurology at the University of Kansas Medical Center. “The Phase 3 study results showed meaningful improvements in respiratory function and walking distance, which are impactful in this serious condition.”