Phase 4 Pompe Study Reported At WORLDSymposium

Michael R. Page, PharmD, RPh

Pompe disease is due to deficient function of the lysosomal acid alpha-glucosidase (GAA) enzyme, resulting in buildup of glycogen in muscle tissue and progressive muscle damage.
In the original ADVANCE prospective open-label study, patients, aged 1 year to 18 years across 52 centers in the United States, received treatment with alglucosidase alfa 160 L, followed by a 52-week treatment phase, and an extension phase with alglucosidase alfa 4000 L.
Researchers noted a primary efficacy outcome of the percentage of patients remaining clinically stable or improving. Secondary outcomes included safety, as well as efficacy, ventilator-free survival, and results on cardiac, respiratory, and motor outcomes.
In the efficacy analysis, of 104 patients who completed the trial up to week 52, 87 patients were stable and did not experience clinical worsening. In patients with infantile-onset Pompe disease (IOPD), 69 of 82 patients were clinically stable, and in patients with late-onset Pompe disease (LOPD), 18 of 22 patients were clinically stable through week 52.
Nearly three-fourths (72%) of the 113 patient in the original ADVANCE study received treatment with alglucosidase alfa 4000 L, with a mean age at first infusion of 4.8 years (range: 1.0-18.7 years).
In the safety and extension periods, a total of 2752 adverse events occurred, of which a minority (168) were related to treatment. Adverse events that were not related to treatment occurred in 66% of patients, and the remaining 34% of patients experienced adverse events that were related to treatment. Treatment-related adverse events occurring in at least 10% of patients included pyrexia (10%), vomiting (4%), diarrhea (4%), nausea (3%), abdominal pain (3%), upper abdominal pain (2%), tachycardia (4%), headache (3%), rash (4%), and cough (3%).
Serious adverse events (both related and unrelated to treatment) included pneumonia, which occurred in nearly one-fourth (22%) of patients, respiratory distress (14% of patients), pyrexia (9% of patients), and device-related infection (5% of patients). Severe adverse events (both related and unrelated to treatment) included pneumonia (11% of patients), respiratory distress (8% of patients), and respiratory failure (6% of patients).
In the transition from alglucosidase alfa 160 L to alglucosidase alfa 4000 L, most patients maintained clinical stability, and the safety profile of alglucosidase alfa 160 L and alglucosidase alfa 4000 L were consistent with product labeling in this open-label phase 4 extension of the ADVANCE clinical trial.


Hahn S, Pena L, Day JW, et al. 52-week efficacy and safety profile of alglucosidase alfa produced at 4000 L scale in US patients with Pompe disease: ADVANCE, a phase 4 open-label prospective study. Poster 123. Presented at: WORLDSymposium 2016, San Diego, California.
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