A Multi-Centre Prospective Study of the Efficacy and Safety of Alglucosidase Alfa in Chinese Patients With Infantile-Onset Pompe Disease

Abstract

Background: A high prevalence of infantile-onset Pompe disease (IOPD) in the Chinese population has been noted, but there are currently no reported clinical trials of enzyme replacement therapy (ERT) for IOPD in this population. The purpose of this study was to evaluate the efficacy and safety of alglucosidase alfa in Chinese patients with IOPD.Materials and Methods: A multicentre, single-arm, prospective, open-label clinical trial was performed at 4 sites in China. Eligible Chinese subjects with IOPD received an infusion of alglucosidase alfa at a dose of 20 mg/kg every 2 weeks for up to 52 weeks. The primary endpoints of clinical efficacy were the survival rate and changes in the left ventricular mass index (LVMI). The safety assessment was based on the incidence of adverse events (AEs).Results: A total of 10 eligible subjects were enrolled in the study. The mean age at the start of ERT was 5.36 ± 1.56 months. Nine subjects had survived after 52 weeks of treatment. One subject discontinued the study and died after mechanical ventilation was withdrawn. The intent-to-treat analysis demonstrated that the survival rate was 90.0% (95% confidence interval: 55.5–99.7%). The mean LVMI at week 52 was 70.59 ± 39.93 g/m2 compared to that of 298.02 ± 178.43 g/m2 at baseline, with a difference of -227.60 ± 155.99 g/m2. All subjects had left ventricular mass (LVM) Z scores >10 at baseline, and eight subjects (80%) achieved Z scores <5 at week 52. No treatment-related AEs were observed, and no AEs led to the discontinuation of treatment.Conclusions: This clinical trial is the first study of ERT for IOPD in China, indicating that alglucosidase alfa has favourable efficacy and safety for the treatment of Chinese patients with IOPD (ClinicalTrials.gov number, NCT03687333).

Efficacy and safety of enzyme replacement therapy with alglucosidase alfa for the treatment of patients with infantile-onset Pompe disease: a systematic review and metanalysis

“…These data were also compared to the same historical controls, with survival at 24 and 36 months of 1.9% (95% CI: 0%–5.5%). Finally, the survival rate of Zhu et al ( 29 ) was 100% ( n = 9, 95% CI: 66.4%–100%).…”

“…Therefore, we only considered the first to be published as its data were completed ( 26 ). Kishnani et al ( 16 ), Nicolino et al ( 28 ) and Zhu et al ( 29 ) showed the beneficial effect of ERT, with reductions in LV mass as follows: −106.6 g/m 2 ( 16 ), −62.7% ( 28 ) and −227.60 ± 155.99 g/m 2 ( 29 ), after ERT respectively.…”

“…These studies also showed that the newborn screened population that started ERT earlier than the clinical cases population start ventilation even later ( P < .001). Zhu et al ( 29 ) showed that only 1/9 subjects used an invasive ventilator during the study. At the end of the study (13 months), all nine survivors were free from the use of any ventilators.…”

“…Zhu et al ( 29 ) had at least one AE reported for each participant. All AEs identified in this study were treatment-emergent AE (TEAEs), and at least one serious TEAE (SAE) was reported for nine subjects (90%).…”

Long-Term Experience with Anaphylaxis and Desensitization to Alglucosidase Alfa in Pompe Disease

“…There are also references, however, that report the prevalence of severe allergic reactions with rhGAA in IOPD as low or absent. One of these is a research study that was conducted for a period of 52 weeks with 10 patients with IOPD who had received 20 mg/kg rhGAA biweekly; no severe adverse reactions were reported [ 17 ]. Another refers to an Italian expert panel review that states that approximately 1% of IOPD patients develop anaphylactic shock and/or cardiac arrest, while 5–14% of patients develop significant allergic reactions with rhGAA that involve at least two or three body systems [ 18 ].…”