Switching to Nexviazyme stabilizes or improves lung function in LOPD
Benefits of switching independent of previous Lumizyme treatment outcomes
Switching from Lumizyme (alglucosidase alfa) to Nexviazyme (avalglucosidase alfa) stabilizes or improves lung function in people with late-onset Pompe disease (LOPD).
That’s according to new analyses from the COMET Phase 3 clinical trial and its open-label extension study, which showed the benefits of switching to Nexviazyme were independent of the outcomes from previous Lumizyme treatment.
“These results may be useful for people with LOPD and their healthcare providers to inform decision making on treatment options,” the researchers wrote in the study, “Efficacy of Switching Therapy From Alglucosidase Alfa to Avalglucosidase Alfa on Respiratory Function in Participants With Late-Onset Pompe Disease: A Post Hoc Analysis From the COMET Trial,” which was published in JIMD Reports. The research team included scientists at Sanofi, which markets both therapies and funded the analysis.
Nexviazyme and Lumizyme, sold respectively as Nexviadyme and Myozyme in Europe, are enzyme replacement therapies (ERT) that contain a lab-made version of acid alpha-glucosidase (GAA), the enzyme missing or defective in Pompe disease. Nexviazyme is designed to enhance the delivery of GAA to muscle cells, which Pompe disease affects.
The COMET Phase 3 trial (NCT02782741) evaluated the efficacy of Nexviazyme over Lumizyme in untreated children and adults with LOPD. The participants were randomly assigned to Nexviazyme or Lumizyme for 49 weeks. Those who completed the main trial could enroll in an open-label extension (OLE) phase, where all were treated with Nexviazyme for more than 4.5 years.
Top-line results showed Nexviazyme outperformed Lumizyme at improving lung function, as assessed by forced vital capacity (FVC), the volume of air that can be forcefully exhaled after a deep breath. The difference wasn’t statistically significant, but early data from the OLE indicated the benefits of Nexviazyme were sustained for up to two years.
Testing lung outcomes after switch to Nexviazyme
In this report, researchers evaluated respiratory outcomes in those who received Lumizyme in COMET and then switched to Nexviazyme in the OLE for up to 145 weeks, or nearly three years.
At the end of COMET, 20 of the 44 participants (45.5%) included in the current study showed a FVC change of more than 0%, and 14 (31.8%) showed an improvement of at least 3%, which is considered clinically meaningful.
In the Lumizyme-treated patients with a change in FVC, the improvement during COMET was 4% per year, and was maintained after switching to Nexviazyme. For those whose FVC declined or didn’t change, the FVC change during COMET worsened by 3.4% per year, which stabilized after switching to Nexviazyme.
Airflow responses, as assessed by forced expiratory volume in one second (FEV1), the amount of air that can be forcibly exhaled in the first second, matched those of FVC. Measures of muscle strength related to breathing in and out showed stability after the switch in those whose FVC worsened.
Among those with a FVC improvement of at least 3%, FVC and FEV1 increased during COMET, and these benefits were maintained or continued improving after switching to Nexviazyme in the OLE. Lung function stabilized after switching among those patients with a lesser change in FVC during COMET.
In blood tests, more patients whose FVC declined or had no change during COMET had higher levels of antibodies against Lumizyme than those whose FVC improved. Similar patterns were seen for those with an improvement or a decline of 3% or more. During the OLE, no participants were found to have high levels of anti-Nexviazyme antibodies.
At the end of COMET, the median urinary HEX4 levels, a marker for glycogen clearance from GAA activity, decreased more in those with an FVC improvement than those with a decline or no change in FVC (22.5% vs. 12.6%). After switching to Nexviazyme, HEX4 levels declined to week 145 in both groups. This trend was similar when using the 3% threshold.
“Data from this post hoc analysis of people with LOPD enrolled in the COMET trial show clinically meaningful maintenance in measures of lung volume (FVC) and airflow (FEV1) after switching therapy from [Lumizyme] to [Nexviazyme] that persists for at least [two] years,” wrote the researchers, who said the finding was “independent of individual participants’ level of benefit from prior treatment with [Lumizyme].”
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