Skip to navigation Skip to main content

Pompe Disease (PD)

PAGE CONTENTS

Lumizyme

Lumizyme® (alglucosidase alfa) is a hydrolytic lysosomal glycogen-specific enzyme indicated for the replacement of the acid alpha-glucosidase (GAA) enzyme in Pompe disease.1,2 GAA is responsible for hydrolyzing lysosomal glycogen into glucose. GAA is absent or deficient in Pompe disease, which results in the buildup of glycogen in the cells, with higher incidence in muscle cells. This leads to muscle weakness and damage to the respiratory and cardiac systems.3 

Enzyme replacement therapy (ERT) is the only available treatment for Pompe disease. This therapy consists of the intravenous infusion of a recombinant human GAA precursor enzyme that is commercialized as Lumizyme in the US and as Myozyme® outside the US.3

Get prescribing information about Lumizyme on Rare Disease Advisor’s drug monograph.

Lumizyme was first approved by the US Food and Drug Administration (FDA) in 2006.2,4 The drug is available as a lyophilized powder in single-dose vials to be prepared as a solution for intravenous infusion. Administration is done every 2 weeks. Frequently reported adverse reactions in clinical trials included anaphylaxis, rash, urticaria, nausea, tachycardia, vomiting, muscle twitching, and myalgia.2

Warnings and Precautions

Anaphylaxis and hypersensitivity reactions have been observed during the infusion of alglucosidase alfa and up to 3 hours after administration. These reactions may be life-threatening, requiring discontinuation of administration and appropriate medical treatment.2 

Therapy with alglucosidase alfa can be affected by the patient’s immune response. The majority of patients with Pompe disease develop antibodies against the protein used in the treatment. This is most severe in patients with infantile-onset Pompe disease (IOPD) that have no GAA activity. These patients are considered cross-reactive immunologic material (CRIM)-negative, and they develop antibodies in high titers that severely compromise therapy.5,6 

Patients presenting with respiratory and cardiac illness can have these conditions exacerbated during infusions with alglucosidase alfa. Doctors may decide to prolong observation during and after drug infusion.1,2

Alglucosidase Alfa Treatment in Infantile-Onset Pompe Disease

The use of ERT in Pompe disease has had an impact on the natural course of the disease, allowing prolonged survival in infants. A strong effect on cardiac function and a less pronounced effect on skeletal muscle have been observed in these patients.7

The safety and efficacy of alglucosidase alfa has been assessed in several clinical trials. These trials involved IOPD patients with a maximum age of 3.5 years at first infusion.2

The first trial was a single-center and open-label study with 18 patients with IOPD that were diagnosed at 6 months of age or younger. Patients received 20 mg/kg of alglucosidase alfa every other week. Analyses at week 52 revealed that patients were alive and did not require ventilatory support. The risks of death and invasive ventilation were decreased by 99% and 92%, respectively. This trial also highlighted the importance of initiating therapeutics at a younger age to improve treatment outcomes.8 Follow-ups performed for up to 3 years showed marked extensions of survival and ventilation-free survival, with improvements in cardiomyopathy.9

A different multicenter, non-randomized, and open-label clinical trial included 21 patients with IOPD that received 20 mg/kg of alglucosidase alfa every other week. The median treatment time was 120 weeks. Patients showed minimal GAA activity and abnormalities in the left ventricular mass index. By the end of the study, 71% of the patients were alive and 44% of the patients did not require ventilatory support. The risks of death and invasive ventilation were reduced by 79% and 58%, respectively. Cardiac function was also improved.10

Alglucosidase Alfa Treatment in Late-Onset Pompe Disease

Evidence of alglucosidase alfa efficacy in late-onset Pompe disease (LOPD) is based on small and uncontrolled studies.11 The Late-Onset Treatment Study (LOTS) was a randomized, multicenter, multinational, placebo-controlled clinical trial that included 90 patients aged between 10 and 70 years old.12 Patients were ambulatory and did not require ventilation. Treatment was performed with 20 mg/kg of alglucosidase alfa every other week for 78 weeks. Results showed that patients had remarkable improvements in walking distance and stabilization of respiratory activity. The trial also included a prior observational study, the Late-Onset Pompe Observational Study (LOPOS), and an extension study after the first 78 weeks.13,14

Other studies highlight the effects of ERT in LOPD,15,16 however, patient response varies. Ambulation is typically improved, and motor and pulmonary functions can also benefit from treatment.7 A more recent review covering 438 patients with LOPD monitored between 3 and 48 months concluded that mortality rate was decreased by 5 times for patients administered ERT compared to untreated patients. Cardiac function improvements are found in the first months of treatment and then a slight decline is observed after 2 to 3 years, contrasting with the constant decline reported in untreated patients.11

References

1. About Lumizyme. Sanofi Genzyme. Accessed July 27, 2021.

2. Lumizyme package insert. Genzyme Corporation. Accessed July 27, 2021. 

3. Colella P, Mingozzi F. Gene therapy for Pompe disease: the time is now. Hum Gene Ther. 2019;30(10):1245-1262. doi:10.1089/hum.2019.109

4. Pompe disease. National Organization for Rare Disorders. Accessed July 27, 2021.

5. Banugaria SG, Prater SN, Ng YK, et al. The impact of antibodies on clinical outcomes in diseases treated with therapeutic protein: lessons learned from infantile Pompe disease. Genet Med. 2011;13(8):729-736. doi:10.1097/GIM.0b013e3182174703

6. van Gelder CM, Hoogeveen-Westerveld M, Kroos MA, Plug I, van der Ploeg AT, Reuser AJJ. Enzyme therapy and immune response in relation to CRIM status: the Dutch experience in classic infantile Pompe disease. J Inherit Metab Dis. 2015;38(2):305-314. doi:10.1007/s10545-014-9707-6

7. Kohler L, Puertollano R, Raben N. Pompe disease: from basic science to therapy. Neurotherapeutics. 2018;15(4):928-942. doi:10.1007/s13311-018-0655-y

8. Kishnani PS, Corzo D, Nicolino M, et al. Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease. Neurology. 2007;68(2):99-109. doi:10.1212/01.wnl.0000251268.41188.04

9. Kishnani PS, Corzo D, Leslie ND, et al. Early treatment with alglucosidase alpha prolongs long-term survival of infants with Pompe disease. Pediatr Res. 2009;66(3):329-335. doi:10.1203/PDR.0b013e3181b24e94

10. Nicolino M, Byrne B, Wraith JE, et al. Clinical outcomes after long-term treatment with alglucosidase alfa in infants and children with advanced Pompe disease. Genet Med. 2009;11(3):210-219. doi:10.1097/GIM.0b013e31819d0996

11. Schoser B, Stewart A, Kanters S, et al. Survival and long-term outcomes in late-onset Pompe disease following alglucosidase alfa treatment: a systematic review and meta-analysis. J Neurol. 2017;264(4):621-630. doi:10.1007/s00415-016-8219-8

12. van der Ploeg AT, Clemens PR, Corzo D, et al. A randomized study of alglucosidase alfa in late-onset Pompe’s disease. N Engl J Med. 2010;362(15):1396-1406. doi:10.1056/NEJMoa0909859

13. Wokke JHJ, Escolar DM, Pestronk A, et al. Clinical features of late-onset Pompe disease: a prospective cohort study. Muscle Nerve. 2008;38(4):1236-1245. doi:10.1002/mus.21025

14. van der Ploeg AT, Barohn R, Carlson L, et al. Open-label extension study following the Late-Onset Treatment Study (LOTS) of alglucosidase alfa. Mol Genet Metab. 2012;107(3):456-461. doi:10.1016/j.ymgme.2012.09.015

15. van Capelle CI, van der Beek NAME, Hagemans MLC, et al. Effect of enzyme therapy in juvenile patients with Pompe disease: a three-year open-label study. Neuromuscul Disord. 2010;20(12):775-782. doi:10.1016/j.nmd.2010.07.277

16. Angelini C, Semplicini C, Ravaglia S, et al. Observational clinical study in juvenile-adult glycogenosis type 2 patients undergoing enzyme replacement therapy for up to 4 years. J Neurol. 2012;259(5):952-958. doi:10.1007/s00415-011-6293-5

Reviewed by Harshi Dhingra, MD, on 7/27/2021.

  • Loading...

    Continuing Medical Education (CME/CE) Courses

    Show More

READ MORE ON PD