FDA Approves Nexviazyme, Next-generation ERT for Late-onset Pompe
The medication, administered by infusion into the bloodstream every two weeks, is approved for patients 1 year or older and is expected to be available in the U.S. in the coming weeks, according to its developer, Sanofi Genzyme.
The recommended dose is based on body weight — 20 mg/kg for patients weighing at least 30 kg (about 66 pounds) or 40 mg/kg for those weighing less.
“Today’s approval brings patients with Pompe disease another enzyme replacement therapy option for this rare disease,” Janet Maynard, MD, a deputy director at the FDA’s Center for Drug Evaluation and Research, said in a press release.
Pompe disease is caused by mutations in the GAA gene, which provides cells with the instructions for making an enzyme needed to break down glycogen. As a result, glycogen — a complex sugar molecule — builds up to abnormal levels in tissues, particularly in muscles, ultimately causing the disease’s symptoms.
Enzyme replacement therapy (ERT) for Pompe disease involves therapeutic administration of a version of the dysfunctional enzyme, thereby allowing glycogen to be broken down.
As a next-generation ERT, Nexviazyme is designed to improve the delivery of the therapeutic enzyme to muscles and enhance glycogen clearance.
It is the second ERT for Pompe disease to be approved by the FDA, the first being Lumizyme (alglucosidase alfa), also developed by Sanofi Genzyme. Lumizyme is approved in Europe, where it is marketed as Myozyme.
The European Commission is currently considering an application to approve Nexviazyme. Sanofi is also seeking approval of the medication in Japan.
The FDA’s approval was supported by positive data from an ongoing Phase 3 clinical trial called COMET (NCT02782741), in which 100 previously untreated patients, 3 and older, with late-onset Pompe disease were randomly assigned to treatment with Nexviazyme or Lumizyme. Both ERTs were administered directly into the bloodstream every other week at a dose of 20 mg/kg for 49 weeks (about a year).
Top-line results from COMET showed that Nexviazyme improved lung function and walking ability. Participants taking Nexviazyme experienced greater respiratory improvements (although not statistically significant) and were able to walk farther than those on Lumizyme.
“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, a professor at the University of Kansas Medical Center, said in another press release.
Patients who complete the initial portion of the trial have the opportunity to enroll in an open-label extension phase, in which they are treated with Nexviazyme and assessed for 240 weeks (about 4.5 years). Data from the extension phase have so far been positive, with 20 patients who switched from Lumizyme to Nexviazyme showing better lung function and mobility at week 97.
Common side effects of Nexviazyme include headache, fatigue, diarrhea, nausea, joint pain, dizziness, muscle pain, itching, vomiting, difficulty breathing, skin redness, feeling of “pins and needles,” and skin welts. Serious allergic reactions and infusion-related reactions have been reported.
Sanofi Genzyme has stated that Nexviazyme will have the same price as Lumizyme. The company offers CareConnectPSS Patient Support Services to provide support for people and families that are affected by Pompe disease, including individuals transitioning to Nexviazyme.
“Nexviazyme is a new and exciting therapeutic option for people with late-onset Pompe disease,” Dimachkie said.
Nexviazyme is also being evaluated in a Phase 2 study called mini-COMET (NCT03019406), which is testing the therapy’s safety and effectiveness in 22 children and adolescents with infantile-onset Pompe disease, all of whom had previously been treated with Lumizyme, but failed to respond adequately. Six-month data indicated that Nexviazyme was well-tolerated, with no severe side effects, and the treatment lowered (or kept stable) disease-associated biomarkers. This trial is expected to end in 2024.
Both COMET and mini-COMET are funded by Genzyme.