Avalglucosidase alfa maintains respiratory function, endurance in late-onset Pompe disease

Key takeaways:

• Forty-six participants continued avalglucosidase alfa through week 97 and 40 switched from alglucosidase alfa.
• Forced vital capacity percent and 6-minute walk test improved in both treatment groups.

Continuous treatment with avalglucosidase alfa, or after a switch from alglucosidase alfa, maintained respiratory function and functional endurance in patients with late-onset Pompe disease, with no new safety concerns reported.

“Pompe disease has a broad clinical spectrum affecting multiple body systems and considerable variation in age at symptom onset and rate of progression,” Priya S. Kishnani, MD, MBBS, Chen Family Distinguished Professor of Pediatrics and chief of medical genetics at Duke University Medical Center, and colleagues wrote in JAMA Neurology. “Since 2006, enzyme replacement therapy with alglucosidase alfa has prolonged life for patients with [infantile-onset Pompe disease] and improved or stabilized disease in patients with [infantile-onset Pompe disease] and [late-onset Pompe disease].”

Analysis of data from the Comparative Enzyme Replacement Trial With neoGAA Versus rhGAA (COMET) trial demonstrated that patients with late-onset Pompe disease treated with avalglucosidase alfa for 49 weeks had significant improvements in upright forced vital capacity and 6-minute walk test compared with alglucosidase alfa, prompting researchers to evaluate safety and efficacy outcomes in the trial’s extension period.

Kishnani and colleagues conducted the phase 3, double-blind randomized clinical trial at 55 referral centers in 20 countries between November 2016 and February 2021. They enrolled patients aged 3 years and older with previously untreated late-onset Pompe disease, who received 20 mg/kg of IV avalglucosidase alfa or alglucosidase alfa every other week for 49 weeks, followed by 20 mg/kg of IV avalglucosidase alfa every other week for up to 289 weeks.

Researchers reported efficacy outcomes at 49, 61, 73 and 97 weeks. Outcomes of interest included least squares (LS) mean change from predicted baseline in forced vital capacity (FVC) percent, as well as LS mean change from baseline in the 6-minute walk test (6MWT), muscle strength, motor function, quality of life and disease biomarkers. Safety and tolerability were also analyzed.

According to results, 95 of the initial 100 participants (54% men; mean age, 48.3 years) completed the 49-week treatment period and entered the extension phase, with 86 individuals continuing treatment through week 97. Of those, 46 continued avalglucosidase alpha and 40 switched from alglucosidase alfa to avalglucosidase alfa.

Researchers reported that mean upright FVC percent predicted was similar between treatment groups at the start of the study, while 6MWT distance was greater in the avalglucosidase alfa group. From baseline to week 97, LS mean FVC percent predicted increased by 2.65 for patients who continued avalglucosidase alfa and 0.36 for those who switched to avalglucosidase alfa, and LS mean 6MWT distance increased by 18.6 and 4.56 meters, respectively.

Data additionally showed that in participants who switched to avalglucosidase alfa, LS mean FVC percent predicted remained stable from week 49 to 97 (change = 0.09) and 6MWT distance improved by 5.33 meters.

Researchers reported potentially treatment-related adverse events in 29 participants in the avalglucosidase alfa continuation group and in 25 patients in the crossover group.

“Data from the ongoing real-world experience with avalglucosidase alfa will provide additional evidence of its effectiveness and safety,” Kishnani and colleagues wrote.