n this criteria mild to moderate patients, presenting heterogeneous severity withability to perform endurance tests, large variability of clinical manifestations and age of onset wereenrolled.
Overall effects of treatment were eva luated in the domains of pharmacodynamics (reduction of serumoligosaccharides), functional (three-minute stair climbing test (3MSCT), six-minute walking test(6MWT), and forced vital capacity (FVC) % predicted) and quality of life (childhood healthassessment questionnaire (CHAQ) disability index (DI) and CHAQ VAS pain (visual analoguescale)).
In the phase 3 pivotal multi-centre, double-blind, randomised, placebo-controlled, parallel group studyrhLAMAN-05, the efficacy and safety of repeated administrations of velmanase alfa over 52 weeks ata dose of 1 mg/kg given weekly as intravenous infusion were investigated. A total of 25 patients wereenrolled, including 12 paediatric subjects (age range: 6 to 17 years; mean: 10.9 years) and 13 adultsubjects (age range: 18 to 35 years; mean: 24.6). All but one patient were naïve to the treatment withvelmanase alfa. In total 15 patients (7 paediatrics and 8 adults) received active treatment and
10 patients received placebo (5 paediatrics and 5 adults). The results (serum oligosaccharideconcentration, 3MSCT, 6MWT and FVC%) are presented in table 2. A pharmacodynamic effect with
statistically significant decrease of serum oligosaccharides in comparison to placebo was
demonstrated. The results observed in patients below 18 years of age showed an improvement. Inpatients over 18 years old a stabilisation has been demonstrated. The numerical improvement of mostclinical endpoints over placebo (2 to 8 %) observed in the year of observation could be suggestive ofthe ability of velmanase alfa to slow down the existing disease progression.
Table 2: Results from placebo-controlled clinical study rhLAMAN-05 (source data:
rhLAMAN-05)
Treatment with
velmanase alfa for 12 months
(n=15)
Treatment with
placebo for 12 months
(n=10)
Velmanase alfa
vs. placebo
Patients Baseline
actual value
Mean (SD)
Absolute
change from
baseline
Mean
Baseline
actual value
Mean (SD)
Absolute
change from
baseline
Mean
Adjusted mean
difference
Serum oligosaccharide concentration (μmol/l)
Overall(1)
[95% CI]
p-value
6.8 (1.2) -5.11
[-5.66; -4.56]
6.6 (1.9) -1.61
[-2.28; -0.94]
-3.50
[-4.37; -2.62]
p<0.001
<18 years(2) 7.3 (1.1) -5.2 (1.5) 6.0 (2.4) -0.8 (1.7) -
≥18 years(2) 6.3 (1.1) -5.1 (1.0) 7.2 (1.0) -2.4 (1.4)
3MSCT (steps/min)
Overall(1)
[95% CI]
p-value
52.9 (11.2) 0.46
[-3.58; 4.50]
55.5 (16.0) -2.16
[-7.12; 2.80]
2.62
[-3.81; 9.05]
p=0.406
<18 years(2) 56.2 (12.5) 3.5 (10.0) 57.8 (12.6) -2.3 (5.4) -
≥18 years(2) 50.0 (9.8) -1.9 (6.7) 53.2 (20.1) -2.5 (6.2)
6MWT (metres)
Overall(1)
[95% CI]
p-value
459.6 (72.26) 3.74
[-20.32; 27.80]
465.7 (140.5) -3.61
[-33.10; 25.87]
7.35
[-30.76; 45.46]
p=0.692
<18 years(2) 452.4 (63.9) 12.3 (43.2) 468.8 (79.5) 3.6 (43.0) -
≥18 years(2) 465.9 (82.7) -2.5 (50.4) 462.6 (195.1) -12.8 (41.6)
FVC (% of predicted)
Overall(1)
[95% CI]
p-value
81.67 (20.66) 8.20
[1.79; 14.63]
90.44 (10.39) 2.30
[-6.19; 10.79]
5.91
[-4.78; 16.60]
p=0.278
<18 years(2) 69.7 (16.8) 14.2 (8.7) 88.0 (10.9) 8.0 (4.2) -
≥18 years(2) 93.7 (17.7) 2.2 (7.2) 92.4 (10.8) -2.8 (15.5)
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