Cipaglucosidase Alfa/Miglustat Shows Beneficial Treatment Effects for Patients With Late-onset Pompe Disease


Most ambulatory patients had improved pulmonary functions and biomarker outcomes with cipaglucosidase alfa/miglustat that were sustained through a less than 36-month follow-up period.

Barry J. Byrne, MD, PhD, associate chair of pediatrics and director, Powell Gene Therapy Center, University of Florida; and chief medical advisor, Muscular Dystrophy Association

Barry J. Byrne, MD, PhD

Over the course of 36 months, cipaglucosidase alfa/miglustat, an investigational treatment from Amicus Pharma for late-onset Pompe disease (LOPD) displayed a safety profile similar to approved enzyme replacement therapy (ERT) and was associated with reduced creatine kinase and urine Hex4.

Barry J. Byrne, MD, PhD, associate chair of pediatrics and director, Powell Gene Therapy Center, University of Florida; and chief medical advisor, Muscular Dystrophy Association, and colleagues presented an abstract on the 36-month efficacy data from the ATB200-02 study (NCT02675465) at the 2022 American Association of Neuromuscular & Electrodiagnostic Medicine Annual Meeting, held September 21-24, in Nashville, Tennessee. Ultimately, they highlight cipaglucosidase alfa/miglustat, also known as AT-GAA, as a beneficial 2-component therapy for Pompe disease.

ATB200-02 enrolled 3 cohorts of ambulatory patients based on ERT experience: those with 2 to 6 years (n=11; aged 18-65 years) or with 7 or more years (n=6; aged 18-75 years) were both administered 20 mg/kg alglucosidase alfa biweekly, and those who were ERT-naïve (n=6; aged 18-65 years) who were given doses of 20 mg/kg IV cipaglucosidase alfa/260 mg miglustat orally biweekly.1

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At 6, 12, 24, and 36 months, integrated analyses of the ERT-experienced cohorts showed improvementsin 6-minute walk distance from baseline of 23.1 m (SD, 44.75; n = 16), 33.5 m (SD, 49.62; n = 16), 21.3 m (SD, 60.90; n = 10), and 47.8 m (SD, 53.80; n = 8), respectively. Comparatively, the ERT-naïve cohort reported improvements of 36.7 m (SD, 29.08; n = 6) at 6 months, 57.0 m (29.96; n = 6) at 12months, 60.7 m (SD, 36.52; n = 5) at 24 months, and 43.5 m (45.19; n = 5) at 36 months.

Percent predicted sitting forced vital capacity (pFVC) was generally stable in the 2 ERT-experienced cohorts, with a mean change from baseline of −0.8% (SD, 8.69; n = 16), −1.3% (SD, 5.95; n = 16), −0.9% (SD, 7.65; n = 10),and −0.4% (SD, 7.56; n = 8) at 6, 12, 24, and 36 months, respectively.In the ERT-naïve cohort,pFVC improved by 5.5% (SD, 5.68; n = 6), 4.5% (SD, 7.92; n = 6), 6.8% (SD, 6.76; n = 5), and 6.2% (SD, 3.42; n = 5) at those same time points, respectively.1 

NeurologyLive® previously had a conversation with Byrne on what role the new therapy might play in the care paradigm for LOPD, as the FDA is set to decide on the therapy’s approval in late October 2022. The therapy consists of cipaglucosidase alfa, and miglustat as an enzyme stabilizer. The therapy had also been assessed in a previous phase 3 trial, called PROPEL (NCT03729362) that compared it with alglucosidase alfa (Lumizyme; Sanofi) and placebo in adults with LOPD.2

“The use of miglustat in combination with cipaglucosidase alfa as a 2-component therapy has the potential to increase the efficacy of ERT for patients with Pompe disease,” Byrne said to NeurologyLive®. “The value in the combination is that miglustat is able to stabilize the ERT in the blood and allow for greater activity of the enzyme inside the cell. Having multiple therapeutic products to evaluate will be important to providers and patients in choosing the best regimen for them. The findings so far show improved function in patients who switch from conventional therapy to AT-GAA. The greatest improvement is in those who were not previously treated with ERT. Similar findings are observed in tests of respiratory function and biomarkers of disease severity.”

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1. Byrne B, Schoser B, Kishnani, et al. Long-term Follow Up of CipaglucosidaseAlfa/Miglustat in Ambulatory Patients with Late-Onset PompeDisease: an open-label phase I/II study (ATB200-02). Presented at: AANEM 2022; September 21-24; Nashville, TN. Abstract104.
2. Schoser B, Roberts M, Byrne BJ, et al. Safety and efficacy of cipaglucosidase alfa plus miglustat versus alglucosidase alfa plus placebo in late-onset Pompe disease (PROPEL): an international, randomised, double-blind, parallel-group, phase 3 trial. Lancet Neurol. 2021;20(12):1027-1037. doi:10.1016/S1474-4422(21)00331-8
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