On August 6, 2021, the U.S. Food and Drug Administration announced it has approved Nexviazyme (avalglucosidase alfa-ngpt) for intravenous infusion for treatment of patients 1 year of age and older with late-onset Pompe disease.
Individuals diagnosed of Pompe disease have an enzyme deficiency that causes the accumulation of a complex sugar, known as glycogen, in heart and skeletal muscles, which leads to muscle weakness and premature death from heart or respiratory failure. Typically, glycogen – the stored form of glucose – digests to release glucose into the bloodstream for use as fuel for the cells.
“Pompe disease is a rare genetic disease that causes premature death and has a debilitating effect on people’s lives,” noted Janet Maynard, M.D., deputy director of the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine in the 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. 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.”
An estimated 3,500 individuals in the United States live with Pompe disease and can come in form of infantile-onset Pome disease (IOPD), which progressively affects muscles over time. LOPD symptoms may occur at any age. However, as a result of the wide spectrum of clinical presentations and progressive feature of the disease, it can take seven to nine years prior to patients receiving the right diagnosis. As the disease grows, individuals with LOPD may need mechanical ventilation to aid breathing or a wheelchair to enhance mobility.
The disease is caused by a dysfunction of the lysosomal enzyme acid alpha-glucosidase (GAA) or a genetic deficiency, which brings about accumulation of complex sugars (glycogen) in muscle cells throughout the body. The buildup of glycogen causes permanent harm to the muscles, including the diaphragm that aids skeletal muscles and respiratory function that impact breathing, mobility and functional endurance.
Nexviazyme, an enzyme substitution therapy, is an intravenous drug that aids reduction of glycogen accumulation. The effectiveness of Nexviazyme for treating Pompe disease was shown in a study of 100 patients who were randomized to use Nexviazyme or another FDA-approved enzyme substitution therapy for Pompe disease. Therapy with Nexviazyme enhanced lung function similar to the enhancement seen with the other treatment.
Nexviazyme is particularly aimed at targeting M6P to enhance cellular enzyme uptake and improve glycogen clearance in target tissues with almost 15-fold increase in M6P content in comparison to algucosidase alfa, the comparator arm in the pivotal study.
The most popular side effects included fatigue, headache, muscle pain (myalgia), dizziness, joint pain (arthralgia), diarrhea, difficulty breathing (dyspnea), nausea, dizziness, vomiting, skin redness (erythema), skin welts (urticaria) and feeling of “pins and needles.” Adverse reactions included hypersensitivity reactions such as infusion-associated and anaphylaxis reactions, including increased body temperature and respiratory illness, and chills. Patients exposed to fluid volume overload or with compromised respiratory or cardiac function may be risk for adverse acute cardiorespiratory failure.
The FDA granted approved this application Priority Review, Fast Track, and Breakthrough Therapy designations. Nexviazyme also collected an orphan drug designation, which offers incentives to aid and improve the development of medications for rare illnesses. The FDA approved Nexviazyme to Genzyme Corporation.