Novel Enzyme Replacement Therapy Gains FDA Approval in Pompe Disease

FDA announced yesterday the approval of avalglucosidase alfa-ngpt, sold as Nexviazyme, an enzyme replacement therapy (ERT) for the treatment of patients 1 year and older with late-onset Pompe disease.

Characterized as an autosomal recessive neuromuscular disorder, Pompe disease is marked by an enzyme deficiency that leads to the accumulation of glycogen, the stored form of glucose, in skeletal and heart muscles. Although glycogen typically breaks down to release glucose into the bloodstream as fuel for cells, its rare accumulation in patients with Pompe disease causes muscle weakness and can prove fatal via respiratory or heart failure implications.

“Pompe disease is a rare genetic disease that causes premature death and has a debilitating effect on people’s lives,” said Janet Maynard, MD, deputy director of the Office of Rare Diseases, Pediatrics, Urologic, and Reproductive Medicine in the FDA’s Center for Drug Evaluation and Research, in a statement.

Designed to address the enzyme deficiency and subsequently reduce glycogen accumulation, avalglucosidase alfa-ngpt was shown in a prior phase 3 randomized, multicenter, multinational, double-blinded study to meet its primary objective of statistically noninferior lung improvement in treatment naive patients randomized to the ERT (n = 51) vs those randomized to receive alglucosidase alfa (n = 49), sold as Lumizyme, another FDA-approved ERT for Pompe disease (P = .0074).

Those of the intervention group also showed borderline superior lung improvement compared with the control group (P = .0626).

Furthermore, patients treated with avalglucosidase alfa-ngpt in the study were shown to exhibit greater improvements in the 6-Minute Walk Test, with positive results for the indication observed for all secondary and other efficacy end points.

In assessing safety, adverse events were reported in 86.3% of the intervention group and in 91.8% of the control group, indicating a more favorable safety profile. The most common adverse effects included headache, fatigue, diarrhea, nausea, joint pain, and dizziness.

“Today’s approval brings patients with Pompe disease another ERT option for this rare disease. The FDA will continue to work with stakeholders to advance the development of additional new, effective, and safe therapies for rare diseases, including Pompe disease,” said Maynard.

The FDA approval of avalglucosidase alfa-ngpt, granted to Genzyme Corporation, follows several designations granted by the FDA to the indication, including fast track, priority review, breakthrough therapy, and orphan drug.