Nexviazyme shows long-term benefits for LOPD patients in trial
Gains in lung function, walking ability, seen over nearly 3 years of treatment
Using Nexviazyme (avalglucosidase alfa) led to sustained improvements in lung function, walking ability, and other motor skills over nearly three years of treatment in people with late-onset Pompe disease (LOPD), according to newly shared results from a global clinical trial.
LOPD patients who switched to Nexviazyme after one year of treatment with Lumizyme (alglucosidase alfa) — an earlier generation Pompe disease therapy — also experienced stabilization or further gains in key clinical outcomes, with no new safety concerns after the transition, the data showed.
“These data support the long-term maintenance of clinically meaningful outcomes with [Nexviazyme] in patients with LOPD,” the researchers wrote.
The study, “Efficacy and safety of avalglucosidase alfa in patients with late‑onset Pompe disease after 145 weeks of treatment during the COMET trial,” was published in the Journal of Neurology. The trial was funded by Sanofi, which markets both Nexviazyme and Lumizyme.
Pompe disease is caused by mutations that lead to lower levels of a functional enzyme called acid alpha-glucosidase. This enzyme is needed to break down glycogen to generate energy in cells. Without it, glycogen builds up to toxic levels in muscle, causing progressive weakness and breathing difficulties.
Enzyme replacement therapies or ERTs, which deliver a working version of the enzyme to the body’s cells, have long been the standard of care in Pompe disease. Lumizyme in 2010 became the first ERT approved in the U.S. for Pompe disease. While the therapy has helped improve or stabilize muscle and lung function, many patients still have shown a gradual decline over time or suboptimal treatment responses.
As next-generation ERT, Nexviazyme was designed to be more effective
Nexviazyme, a next-generation ERT approved in the U.S. in 2021 for LOPD, was designed to be more effective than Lumizyme in delivering the enzyme to muscle cells and lowering glycogen levels.
To test the therapy’s benefits against Lumizyme, the Phase 3 COMET clinical trial (NCT02782741) was launched in 2016. Through 2021, it enrolled 100 people with LOPD, ages 3 and older, who had not previously received any treatment. In the first 49 weeks, or nearly one year, participants were randomly assigned to receive intravenous, or into-the-vein, infusions of either Lumizyme or Nexviazyme every other week.
Results shared in 2020 showed a trend toward greater improvements in measures of lung function, walking ability and other motor outcomes. The data also indicated a slightly more favorable safety profile for Nexviazyme compared with Lumizyme, although the differences were not statistically significant.
After this initial phase, all participants could decide to continue treatment with Nexviazyme in the study’s open-label extension. In total, 95 patients entered this phase.
Building on results presented previously, the researchers now have shared long-term safety and efficacy data after 145 weeks, or nearly three years, of treatment in the COMET trial. A total of 49 participants were on Nexviazyme throughout these years, whereas 40 switched from Lumizyme to Nexviazyme.
New data show treatment benefits still in effect after 145 weeks
At week 145, or more than 2.5 years after starting treatment, participants in both groups maintained improvements in their mean forced vital capacity (FVC) — a standard measure of lung function that reflects how much air a person can forcibly exhale after taking a deep breath — compared with their levels at the trial’s start.
In the Nexviazyme arm, FVC values remained above initial values throughout this period, while in the switch arm, lung function showed a slight additional gain after patients moved from Lumizyme to Nexviazyme.
Breathing muscle strength — assessed by maximum inspiratory pressure and maximum expiratory pressure — improved in both groups. The switch arm, however, showed greater gains after transitioning to Nexviazyme, achieving outcomes at least similar to those observed in patients who had received Nexviazyme from the beginning of the study.
Walking ability and motor function were likewise sustained over nearly three years of treatment. At week 145, participants who remained on Nexviazyme walked about 20 meters (nearly 65 feet) farther in the six-minute walk test compared with the study’s start. In contrast, walking distance in the switch arm remained essentially stable after the switch.
Other measures of muscle strength and motor function followed a similar pattern, as the Nexviazyme group showed consistent improvements in more measures than the switch group.
Stability after switching [from Lumizyme] and [an] apparent catch-up effect on some parameters support [Nexviazyme] for second-line treatment of LOPD and suggest that earlier initiation of [Nexviazyme] may be beneficial.
“Because [Lumizyme] is known to yield lower cellular enzyme uptake compared with [Nexviazyme], incomplete degradation of glycogen during the 49 weeks of [Lumizyme] treatment may have allowed some continued disease progression at the cellular level,” the researchers wrote.
However, “the stability after switching and apparent catch-up effect on some parameters support [Nexviazyme] for second-line treatment of LOPD and suggest that earlier initiation of [Nexviazyme] may be beneficial,” the team wrote.
Markers of disease burden also improved, with both groups showing reductions to at least near the normal range in urinary HEX4 — a marker of glycogen buildup — and blood serum creatine kinase, a marker of muscle damage, over the 145 weeks.
Patients can ‘safely switch’ from Lumizyme to Nexviazyme: Researchers
Safety findings showed Nexviazyme was generally well tolerated, with no new safety concerns identified during long-term follow-up. The rates of adverse events potentially related to treatment were similar in both groups, as were adverse events leading to treatment discontinuation and infusion reactions.
Importantly, switching from Lumizyme to Nexviazyme did not result in an increased risk of adverse events or a heightened immune response, according to the researchers.
“The fact that switch participants did not have an increase in adverse events or immunogenicity after switching demonstrates that patients with LOPD can safely switch from [Lumizyme] to [Nexviazyme] in a clinical setting,” the researchers wrote.
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