Therapeutic advancement in Pompe disease

Prof. Antonio Toscano (University of Messina, Italy) gave a comprehensive overview of recent advances in therapies for hereditary myopathies, focusing on Pompe disease. The presentation included a detailed analysis of multiple clinical trials, highlighting the efficacy and safety of enzyme replacement therapies (ERT) and novel therapeutic approaches.

There has been a rapid evolution of therapies for hereditary myopathies, with new molecular approaches offering promising advances [1]. Antisense oligonucleotides and ERT have already radically changed diseases such as Duchenne muscular dystrophy (DMD) and Pompe disease. Additionally, RNA toxicity reduction strategies in myotonic dystrophy type 1 and facioscapulohumeral muscular dystrophy are emerging as potential therapies.

A historical randomised study involving 90 patients with late-onset Pompe disease evaluated the impact of biweekly intravenous alglucosidase alfa (20 mg/kg) over 78 weeks [2]. Results showed significant improvements in the 6-minute walk test and stabilisation of forced vital capacity (FVC). The study concluded that alglucosidase alfa improves walking distance and maintains pulmonary function over 18 months.

More recently, the COMET trial compared the ‘next-generation ERT’ avalglucosidase alfa with alglucosidase alfa in 100 treatment-naïve late-onset Pompe disease (LOPD) patients [3]. The primary outcome was the change in FVC% from baseline to week 49. Avalglucosidase alfa demonstrated clinically meaningful improvements in respiratory function and ambulation, proving non-inferior to alglucosidase alfa with no safety concerns reported.

Further analysis from the COMET trial revealed sustained clinical outcomes for patients on avalglucosidase alfa, with FVC% stabilisation over 145 weeks [4]. Disease-specific and general patient-reported outcomes indicated significant improvements in daily activities, disease symptoms, respiratory function, and mobility. These long-term results have led to a new EPOC consensus paper on the use of ERT for LOPD [5].

In parallel with COMET, the PROPEL trial assessed cipaglucosidase alfa plus miglustat versus alglucosidase alfa plus placebo in LOPD patients [6]. Despite not achieving statistical superiority in improving the 6MWT distance, cipaglucosidase alfa plus miglustat showed potential for long-term efficacy and safety, warranting further investigation.

Prof. Toscano also presented a study on safety and patient satisfaction of home-based intravenous ERT for Pompe disease and mucopolysaccharidosis type I during the COVID-19 pandemic [7]. The findings support home therapy as a viable alternative, maintaining treatment compliance and safety.

To conclude, Prof. Toscano summarised the promising developments and ongoing challenges in the treatment of myopathies. He underscored the importance of personalised and long-term treatment strategies. There is still a need for reliable biomarkers to monitor disease progression and therapeutic efficacy in clinical trials.

1. Toscano A. The landscape of new treatments in hereditary myopathies. 10th EAN Congress, 29 June–2 July 2024, Helsinki, Finland.
2. van der Ploeg AT, et al. N Engl J Med 2010 Apr 15;362(15):1396-406.
3. Diaz-Manera J, et al. Lancet Neurol. 2021 Dec;20(12):1012-1026.
4. Kishnani PS, et al. JAMA Neurol. 2023 Jun 1;80(6):558-567.
5. Schoser B, et al. Eur J Neurol. 2024 Jun 14:e16383.
6. Schoser B, et al. Lancet Neurol. 2021 Dec;20(12):1027-1037.
7. Toscano A, et al. Orphanet J Rare Dis. 2023 Oct 27;18(1):338.

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Posted on 25 July 202426 July 2024