FDA approves Nexviazyme™ (avalglucosidase alfa-ngpt), an important new treatment option for late-onset Pompe disease
News in Brief
- Approval is based on positive Phase 3 data demonstrating improvements in key disease burden measures and establishing its safety profile
- Nexviazyme specifically targets the M6P receptor, the key pathway for enzyme replacement therapy, to effectively clear glycogen build-up in muscle cells
NEXVIAZYME (avalglucosidase alfa-ngpt) is used for the treatment of patients 1 year of age and older with late-onset Pompe disease [lysosomal acid alpha-glucosidase (GAA) deficiency].
WARNING: SEVERE HYPERSENSITIVITY REACTIONS, INFUSION-ASSOCIATED REACTIONS, and RISK OR ACUTE CARDIORESPIRATORY FAILURE IN SUSCEPTIBLE PATIENTS
Hypersensitivity Reactions Including Anaphylaxis
If you are taking NEXVIAZYME, you should know that severe and potentially life-threatening allergic-type reactions known as anaphylaxis and severe hypersensitivity reactions may occur during and after NEXVIAZYME treatment. You should seek immediate medical care if signs and symptoms of anaphylaxis or hypersensitivity reactions occur. If such a reaction is severe enough, your doctor may decide to immediately discontinue the infusion and provide immediate medical care. Appropriate medical support measures may be administered during your infusion, and you may require close observation during and after NEXVIAZYME administration.
Infusion-Associated Reactions (IARs)
If you are taking NEXVIAZYME, you should know that severe IARs may occur during and after NEXVIAZYME treatment. If severe IARs occur during your NEXVIAZYME infusion, your doctor may decide to immediately discontinue the infusion and provide appropriate medical care. If you have an acute underlying illness at the time of NEXVIAZYME infusion you may be at greater risk for IARs. If you have advanced Pompe disease you may have compromised heart and breathing function, which may put you at a higher risk of severe complications from IARs.
Risk of Acute Cardiorespiratory Failure in Susceptible Patients
If you are likely to develop fluid volume overload, or have acute underlying breathing problems or compromised heart or breathing function that may require fluid restriction, there may be a risk of worsening of your heart or breathing status during NEXVIAZYME infusion. Your doctor may decide that close observation during NEXVIAZYME administration may be necessary.
Nexviazyme has demonstrated improvements for people living with late-onset Pompe disease. In the pivotal Phase 3 trial (COMET), Nexviazyme showed improvements in respiratory function and walking distance measures in people with LOPD and established its safety profile.
- When compared to baseline, patients treated with Nexviazyme had a 2.9-point improvement (SE=0.9) in forced vital capacity (FVC) percent-predicted at Week 49, the study’s primary endpoint. Patients treated with Nexviazyme had a 2.4-point greater improvement in FVC percent-predicted compared to patients treated with alglucosidase alfa at Week 49 meeting the measurement of non-inferiority (p=0.0074; 95% CI, -0.13, 4.99). Statistical superiority of Nexviazyme over alglucosidase alfa was not achieved (p=0.06).
- A key secondary endpoint in the trial measured functional endurance with the 6-minute walk test (6MWT). When compared to baseline, patients treated with Nexviazyme walked 32.2 meters farther (SE=9.9) at Week 49. Patients treated with Nexviazyme walked 30 meters farther (95% CI, 1.33, 58.69) than patients treated with alglucosidase alfa at Week 49. Per the hierarchy of the study protocol, formal statistical testing for all secondary endpoints was not conducted.
- In the clinical trial, serious adverse reactions were reported in 1 patient treated with NEXVIAZYME and in 3 patients treated with alglucosidase alfa.
- The most common side effects reported by people receiving NEXVIAZYME were headache, fatigue, diarrhea, nausea, joint pain, dizziness, muscle pain, itching, vomiting, shortness of breath, rash, “pins-and-needles” sensation, and hives.
- In addition, 13 (25%) of people receiving NEXVIAZYME experienced mild-to-moderate Infusion-Associated Reactions (IARs). These reactions included headache, diarrhea, itching, hives, and rash. No one experienced a severe infusion-associated reaction.
"Pompe disease is a debilitating and progressive condition that significantly inhibits mobility and breathing. 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.”
Executive Vice President of Sanofi Genzyme
"Nexviazyme is a new and exciting therapeutic option for people with late-onset Pompe disease. The Phase 3 study results showed meaningful improvements in respiratory function and walking distance, which are impactful in this serious condition.”
Mazen M. Dimachkie, MD, FAAN, FANA
Professor of Neurology and Executive Vice Chair of the Neuromuscular Division in the Department of Neurology at University of Kansas Medical Center
Warnings and Precautions
- Hypersensitivity Reactions Including Anaphylaxis: Life-threatening hypersensitivity reactions, including anaphylaxis, were observed in NEXVIAZYME-treated patients. Some of the hypersensitivity reactions were related to the immune system. Symptoms of anaphylaxsis may include difficulty breathing, chest discomfort, flushing/feeling hot, cough, redness of the skin, lip swelling, itching, swollen tongue, difficulty swallowing, and rash. Symptoms of severe hypersensitivity reactions may include difficulty breathing, redness of the skin, hives, swollen tongue, and rash. Your doctor may decide to give you antihistamine, anti-fever and/or steroid medications before your infusions.
- Infusion-Associated Reactions (IARs): In clinical studies, IARs were observed during and/or within a few hours after the NEXVIAZYME infusion. Symptoms of IARs that required stopping the infusion included chest discomfort, cough, dizziness, redness of the skin, flushing/feeling hot, nausea, redness of the eye, and difficulty breathing. Your doctor may decide to give you antihistamine, anti-fever and/or steroid medications before your infusions to decrease the risk of IARs; however, IARs may still occur after receiving these medications.
- Risk of Acute Cardiorespiratory Failure in Susceptible Patients: If you are likely to develop fluid volume overload, or have acute underlying breathing problems or compromised heart or breathing function that may require fluid restriction, there may be a risk of worsening of your heart or breathing status during NEXVIAZYME infusion, and your doctor may decide that close observation during and after NEXVIAZYME administration may be necessary.
The most common adverse reactions (>5%) were headache, fatigue, diarrhea, nausea, joint pain, dizziness, muscle pain, itching, vomiting, shortness of breath, rash, “pins-and-needles” sensation, and hives.
Please see the full Prescribing Information for complete details, including boxed WARNING.