FDA Approves Sanofi's Next-Generation Enzyme Replacement Therapy Nexviazyme as Potential New Standard of Care for Late-Onset Pompe Disease

On August 6, 2021, the U.S. FDA announced the approval of Sanofi’s enzyme replacement therapy (ERT), Nexviazyme (avalglucosidase alfa-ngpt), for the treatment of patients aged 1 year and older with late-onset Pompe disease (LOPD). Pompe disease is a progressive, debilitating muscle disorder that impairs mobility and respiratory function. Nexviazyme specifically targets the mannose-6-phosphate (M6P) receptor, which serves as a key pathway for cellular uptake. Previously, Nexviazyme had been granted Breakthrough Therapy designation and Fast Track designation by the FDA for the treatment of Pompe disease.

Pompe disease is caused by a genetic deficiency or dysfunction of lysosomal acid α-glucosidase (GAA). This deficiency leads to glycogen accumulation in muscle cells throughout the body, resulting in irreversible damage to various muscles, including the diaphragm that supports respiratory function, and skeletal muscles that affect physical activity, functional endurance, and respiration.

The M6P receptor is the key pathway for delivering the GAA enzyme to intracellular lysosomes. Compared with the standard-of-care α-glucosidase, Nexviazyme contains approximately 15-fold higher M6P content, designed to improve cellular uptake of the enzyme and enhance targeted glycogen clearance.

▲ Impaired glycogen degradation in patients with Pompe disease (Image source: pompe.com)

This approval is based on the positive results obtained from the pivotal Phase 3 clinical trial COMET. The trial data demonstrated that Nexviazyme can improve walking distance and respiratory function parameters in patients. The specific primary results are as follows:

• At Week 49, the trial met the primary endpoint of improved respiratory function. Specifically, compared with baseline, the Nexviazyme group showed a 2.9-point improvement in percent predicted forced vital capacity (FVC percent predicted) (SE=0.9). Compared with the control group, the Nexviazyme group demonstrated a 2.4-point improvement in percent predicted FVC, meeting the noninferiority criterion (p=0.0074; 95% CI, -0.13, 4.99), but not achieving statistical superiority (p=0.06).
• For the key secondary endpoint measuring patients' functional endurance and mobility via the 6-minute walk test (6MWT), at Week 49, the change from baseline in walking distance for the Nexviazyme group was 32.2 meters (SE=9.9, 95% CI: 1.33, 58.69), which was 30 meters greater than that of the active control group.
• In terms of safety, during the 49-week double-blind active-controlled period, serious adverse reactions were reported in 2 patients (2%) in the Nexviazyme group and 3 patients (6%) in the control group. The most frequently reported adverse reactions (>5%) in the Nexviazyme group were headache, pruritus, nausea, urticaria, and fatigue. Infusion-related reactions were reported in 13 patients (25%) in the Nexviazyme group and 16 patients (33%) in the control group. Most infusion-related reactions reported in the Nexviazyme group were mild to moderate, including headache, diarrhea, pruritus, urticaria, and rash. No severe infusion-related reactions were reported.

Note: The original text has been abridged.

References:

[1] FDA approves Nexviazyme^® (avalglucosidase alfa-ngpt), an important new treatment option for late-onset Pompe disease. Retrieved August 6, 2021, from https://www.globenewswire.com/news-release/2021/08/06/2276588/0/en/FDA-approves-Nexviazyme-avalglucosidase-alfa-ngpt-an-important-new-treatment-option-for-late-onset-Pompe-disease.html

[2] FDA Approves New Treatment for Pompe Disease. Retrieved August 6, 2021, from https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-pompe-disease

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