Profile of alglucosidase alfa in the treatment of Pompe disease: safety, efficacy, and patient acceptability

Figures & data

Table 1 Clinical features of classic and non-classic Pompe patients

Organ system	Symptoms of Pompe disease
Skeletal muscle	Classic form: Floppy infant, delayed motor milestones Non-classic form: Proximal muscle weakness (limb girdle) Exercise intolerance Axial weakness, rigid spine^Citation83 “Dropped head” Rare: IBM-like phenotype^Citation9,Citation84 Preclinical, isolated hyper-CK-emia^Citation10
Pulmonary function	Respiratory failure/hypoxia Respiratory infections Diaphragmatic weakness^Citation83,Citation85 Exertional dyspnea Hypercapnia Sleep apnea^Citation86
Heart	Classic form: Cardiomyopathy, cardiac insufficiency Short PR interval, high QRS voltage One infant case of Wolff–Parkinson–White syndrome Non-classic form: Rare cardiac involvement^Citation87 One adult case of Wolff–Parkinson–White syndrome
Skeletal system	Scoliosis^Citation83,Citation88 Osteoporosis Fractures^Citation89 Feet deformities, contractures^Citation90
Other organs	Classic form: hepatomegaly Non-classic form: hepatomegaly only reported in the childhood and juvenile onset Pompe disease, not in adults Macroglossia Gastrointestinal symptoms Hearing loss^Citation91,Citation92 Artheriopathy (aneurysms)^Citation93 Rare: tongue weakness^Citation94 Oropharyngeal dysphagia^Citation95 Ptosis^Citation96
CNS/PNS	Cognitive impairment^Citation97 Rare: small fibre neuropathy^Citation98

Abbreviations: CK, creatine kinase; CNS, central nervous system; PNS, peripheral nervous system.

Figure 1 Histological findings in Pompe disease.

Notes: Muscle biopsy sections of a patient with genetically confirmed Pompe disease presenting as vacuolar myopathy in H&E staining (A). Elevated lysosomal activity is marked by acid phosphatase reaction (B) in the numerous vacuoles that are loaded with glycogen detected by periodic acid Schiff (PAS) stain (C). Magnification 200×.
Abbreviation: H&E, hematoxylin and eosin.

Table 2 Efficacy of ERT in infantile Pompe disease – study summary

Year of study	Number of participants	Age at start of ERT (months)	Duration of ERT (months)	CRIM status	Survival	LVMI reduction	Achieving motor milestones	Ventilator free	Alternative ERT dose to 20 mg/kg body weight	AE	Study
2009	18	2.7–14.6	13–36	4/18 negative	13/18	17/18	11/18	9/18	10–40 mg	11/18	Kishnani et al^Citation33,Citation34
		2	2.5	N/K	Yes	Yes	Yes	Yes	No	Yes	But et al^Citation99
2010	20	0.5–32	1–102	N/K	14/20	N/K	4/10^c	7/20	N/K	N/K	Chakrapani et al^Citation100
		0.8	26	N/K	Yes	Yes	Yes	Yes	No	No	Del Rizzo et al^Citation101
		2	44	Negative	Yes	Yes	Yes	Yes	No	Yes	Rohrbach et al^Citation102
2012	2	6	48	1 negative	Yes	Yes	Yes	Yes	No	No
		0.2	24	1 negative	Yes	Yes	Yes	Yes	No	Yes	Khallaf et al^Citation103
		4.2	36	1 negative^a	No	Yes	No	No	After 1 year highdose	N/K	Banugaria et al^Citation104
	4	N/K	24	N/K	4/4	4/4	4/4	N/K	No	No	Cho et al^Citation105
		5	84	N/K	Yes	Yes	Yes^b	No	After 5 years 20 mg/week	No	Amartino and Cavagnari^Citation106
2013	5	0–9	1–48	N/K	2/5	4/5	3/5	2/5	No	N/K	Fathalla and Ahmed^Citation107
2014		5	36	1 positive^a	Yes	Yes	No	No	After 1 year 40 mg	Yes	Markic et al^Citation44,Citation108
2015	10	0.25–1	28–90	10 positive	10/10	10/10	10/10	10/10	No	N/K	Chien et al^Citation38
	23	0–9.3	30	9 positive	5/9	N/K	8/9	5/9	4/9 40 mg, 1/9 80 mg
				2 negative	0/2	N/K	0/2	1/2	1/2 40 mg
				12 N/K	8/12	N/K^d	8/12	4/12	4/12 40 mg, 2/12 30 mg	8/23	Hahn et al^Citation36
	11	0.1–8.3	48	8 positive	8/8	8/8	6/8	5/8	7/8 40 mg	8/8
				3 negative	0/3	2/3	2/3	1/3	1/3 40 mg	2/3	Van Gelder et al^Citation40

Notes: ^aImmunomodulation treatment; ^bmotor milestones achieved, but lost after third year; ^cmotor mile stones reported only for 10 patients >1 year of age; ^dechocardiographic data available after 6 months of ERT show reversal of cardiac hypertrophy in 14/15 patients.

Abbreviations: AE, adverse events; CRIM, cross-reacting immunological material; ERT, enzyme replacement therapy; LVMI, left ventricular mass index; N/K, not known.

Table 3 Efficacy of ERT in non-classic Pompe disease – study summary

Year of study	Total number of participants	Motor performance (6MWT) (n) increase/unchanged/decline	Respiration, FVC, FEV1 (n) increase/unchanged/decline	Ventilation (n)	AE (n)	Study
Up to 2012	368	(122) 77.9%/8.2%/13.9%	(124) 51.5%/13.7%/34.7%	N/K	(303) 30	Toscano and Schoser^Citation51
2012	69	N/K	(62) Stable	(25) 8 NIV reduced 1 NIV stopped 14 NIV stable 2 NIV intensified
				2 NIV started	(69) 12	de vries et al^Citation61
2013	6	N/K	(6) 50%/0%/50%	(6) 3 NIV stable 1 NIV started	N/K	Schneider et al^Citation86
2014	1	Stable	Improved	Stable	None	Isayama et al^Citation109
	4	(4) 50%/50%/0%	(4) 50%/0%/50%	N/K	N/K	Andreassen et al^Citation54
	8	(8) 87%/12.5%/0%	(8) Stable	2 NIV reduced	(8) 1	Deroma et al^Citation56
	59	(20) Improved	(N/K) Stable	N/K	(59) 3	Anderson et al^Citation52
2015	14	(12) 58.3%/8.3%/33.3%	(12) 16.6%/25%/58.3%	N/K	None	Montagnese et al^Citation9
	5	(5) 20%/60%/20%	(5) 20%/60%/20%	4 NIV stable	(5) 2	Park et al^Citation110

Abbreviations: AE, adverse events; ERT, enzyme replacement therapy; FVC, forced vital capacity; FEV₁, forced expiratory volume in 1 second; 6MWT, 6-Minute Walk Test; NIV, non-invasive ventilation; N/K, not known; n, number of participants for which results were available.

Table 4 Adverse events (AE) and severe adverse events (SAE) reported under ERT

AE	SAE
Infusion-associated reactions:	Anaphylactic reaction^Citation52
Erythema, exanthema, itch, pruritus	Cardiac arrest
	Bronchospasm^Citation111
Flushing	Severe emphysema and pneumothorax^Citation112
Tachycardia	Severe tracheal hemorrhage^Citation113
Chest discomfort	Serious pneumothorax^Citation114
Hypertension	Severe tongue edema^Citation49
Reduced oxygen saturation	Acute hearing loss^Citation115
Globus pharyngis
Vomiting
Flu-like symptoms
Pyrexia, chills
Hyperhidrosis
Muscle cramps

Abbreviation: ERT, enzyme replacement therapy.

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