New Enzyme Therapy OK’d for Pompe Disease

The FDA approved avalglucosidase alfa-ngpt (Nexviazyme) on Friday as a new enzyme replacement therapy for Pompe disease.

Avalglucosidase alfa is an intravenous drug that targets the M6P receptor, and is indicated for late-onset disease for those ages 1 year and older. In patients with the disease, which is marked by dysfunction of the lysosomal enzyme acid alpha-glucosidase, glycogen build-up in skeletal and muscle tissue leads to muscle weakness and respiratory or heart failure.

“Pompe disease is a rare genetic disease that causes premature death and has a debilitating effect on people’s lives,” said Janet Maynard, MD, of FDA’s Center for Drug Evaluation and Research. “Today’s approval brings patients with Pompe disease another enzyme replacement therapy option for this rare disease.”

Support for approval came from the phase III COMET trial, which randomized 100 people with treatment-naive late-onset Pompe disease to either avalglucosidase alfa or alglucosidase alfa, another approved enzyme replacement therapy.

The trial met its primary endpoint, with patients on avalglucosidase alfa seeing a 2.9% absolute improvement in forced vital capacity (FVC) at week 49 compared with baseline. This met criteria for non-inferiority, demonstrating a numerical 2.4% absolute advantage in FVC over alglucosidase alfa (95% CI -0.13 to 4.99, P=0.0074), but superiority was not achieved (P=0.06).

For 6-minute walk test, a key secondary endpoint, patients on avalglucosidase alfa were able to walk 32.2 m farther by week 49 as compared with baseline, and 30 m farther compared with the control arm (95% CI 1.33-58.69), though the study design precluded formal statistical testing for this endpoint.

“Nexviazyme is a new and exciting therapeutic option for people with late-onset Pompe disease,” said COMET investigator Mazen Dimachkie, MD, of the University of Kansas Medical Center in Kansas City, in a statement from Sanofi. “Results showed meaningful improvements in respiratory function and walking distance, which are impactful in this serious condition.”

Late-onset Pompe disease can present at any age, and often takes multiple years before a correct diagnosis can be made due to the disease’s progressive nature and “wide spectrum of clinical presentations,” according to the drugmaker.

Serious adverse events (AEs) with avalglucosidase alfa during COMET included hypersensitivity reactions such as anaphylaxis or infusion-associated reactions and were reported in 2% of patients, as compared with 6% of controls. Infusion reactions were similar between the two arms (25% vs 33%, respectively). Common AEs with avalglucosidase alfa included arthralgia, diarrhea, dizziness, erythema, fatigue, headache, pruritus, myalgia, nausea or vomiting, paresthesia, and urticaria.

FDA cautioned that patients who are “susceptible to fluid volume overload or with compromised cardiac or respiratory function may be at risk for serious acute cardiorespiratory failure” with avalglucosidase alfa.