The Food and Drug Administration (FDA) has approved Nexviazyme (avalglucosidase alfa-ngpt), a hydrolytic lysosomal glycogen-specific enzyme, for the treatment of late-onset Pompe disease in patients 1 year of age and older.
Pompe disease is a rare, degenerative muscle disorder caused by mutations in the acid alpha-glucosidase (GAA) gene, which leads to the abnormal buildup of glycogen in tissues and subsequent organ impairment. Nexviazyme is a GAA enzyme replacement therapy designed for enhanced mannose-6-phosphate (M6P)-receptor targeting and enzyme uptake to increase glycogen clearance.
The approval was based on data from the multicenter, randomized, double-blind phase 3 COMET trial (ClinicalTrials.gov Identifier: NCT02782741), which assessed the efficacy and safety of Nexviazyme in 100 treatment-naïve patients with late-onset Pompe disease. Patients were randomly assigned 1:1 to receive Nexviazyme (n=51) or alglucosidase alfa (n=49) administered as an intravenous infusion every 2 weeks. The primary endpoint was the change from baseline in percent predicted forced vital capacity (FVC) in an upright position.
Results showed that treatment with Nexviazyme met the primary endpoint achieving noninferiority to alglucosidase alfa with a 2.43% (95% CI, -0.13, 4.99) greater increase in FVC percent-predicted at week 49 (P =.0074); Nexviazyme did not achieve statistical superiority over alglucosidase alfa. Patients treated with Nexviazyme achieved a 30.0 meter (95% CI, 1.3-58.7) greater increase in the 6-Minute Walk Test (key secondary endpoint) at week 49 compared with those treated with alglucosidase alfa.
As for safety, Nexviazyme carries a Boxed Warning regarding severe hypersensitivity reactions including anaphylaxis, infusion-associated reactions, and a risk of acute cardiorespiratory failure in susceptible patients. Patients susceptible to fluid volume overload, or those with acute underlying respiratory illness or compromised cardiac or respiratory function for whom fluid restriction is indicated may be at risk of serious exacerbation of their cardiac or respiratory status during infusion.
The most common adverse reactions for Nexviazyme (incidence greater than 5%) include headache, fatigue, diarrhea, nausea, arthralgia, dizziness, myalgia, pruritus, vomiting, dyspnea, erythema, paresthesia and urticaria.
“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.”
Nexviazyme is supplied as a single-dose vial containing 100mg of avalglucosidase alfa-ngpt as a lyophilized powder for reconstitution and is expected to be available in the coming weeks.
- FDA approves new treatment for Pompe disease. News release. US Food and Drug Administration. Accessed August 6, 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-pompe-disease.
- FDA approves Nexviazyme® (avalglucosidase alfa-ngpt), an important new treatment option for late-onset Pompe disease. News release. Sanofi Genzyme. Accessed August 6, 2021. https://www.sanofi.com/en/media-room/press-releases/2021/2021-08-06-17-42-21-2276588.
- Nexviazyme [package insert]. Cambridge, MA: Genzyme Corporation; 2021.