verall: adjusted mean change and adjusted mean difference estimated by ANCOVA model arepresented
(2)By age: unadjusted mean and SD are presented.
The long-term efficacy and safety of velmanase alfa was investigated in the uncontrolled, open label,phase 3 clinical study rhLAMAN-10 in 33 subjects (19 paediatrics and 14 adults, from 6 to 35 years attreatment initiation) who previously participated in velmanase alfa studies. An integrated database wascreated by pooling cumulative databases from all studies with velmanase alfa. Statistically significantimprovements were detected in serum oligosaccharide levels, 3MSCT, pulmonary function, serum IgG and EQ-5D-5L (euro quality of life-5 dimensions) over time, up to the last observation (table 3).
Theeffects of velmanase alfa were more evident in patients younger than 18 years.
Table 3: Change of clinical endpoints from baseline to the last observation in rhLAMAN-10
study (source data: rhLAMAN-10)
Parameter Patients
n=33
Baseline
actual value
Mean
(SD)
Last
observation
% change from
baseline
(SD)
p-value
[95% CI]
Serum oligosaccharide
concentration (µmol/L)
Overall 6.90
(2.30)
-62.8
(33.61)
<0.001
[-74.7; -50.8]
3MSCT (steps/min) Overall 53.60
(12.53)
13.77
(25.83)
0.004
[4.609; 22.92]
6MWT (metres) Overall 466.6
(90.1)
7.1
(22.0)
0.071
[-0.7; 14.9]
FVC (% of predicted) Overall 84.9
(18.6)
10.5
(20.9)
0.011
[2.6; 18.5]
Data suggest that the beneficial effects of the treatment with velmanase alfa diminish with the increase
of disease burden and disease-related respiratory infections.
A post-hoc multiparametric responders analysis supports the benefit of longer treatment with
velmanase alfa in 87.9% of responders in at least 2 domains at last observation (table 4).
Table 4: Multiparametric responder analysis: MCID(1) Responders Rates by Endpoints and
Domains (source data: rhLAMAN-05; rhLAMAN-10)
Domain Criterion
Responders Rates
rhLAMAN-05 study
n=25
rhLAMAN-10 study
n=33
Placebo
12 months
Lamzede
12 months
Lamzede
Last Observation
Pharmacodynamic Oligosaccharides 20.0% 100% 91.0%
Pharmacodynamic Domain
Response Oligosaccharides 20.0% 100% 91.0%
Functional 3MSCT 10.0% 20.0% 48.5%
6MWT 10.0% 20.0% 48.5%
FVC (%) 20.0% 33.3% 39.4%
Functional Domain Response Combined 30.0% 60.0% 72.7%
Quality of Life CHAQ-DI 20.0% 20.0% 42.2%
CHAQ-VAS 33.3% 40.0% 45.5%
QoL Domain Combined 40.0% 40.0% 66.7%
Overall response Three domains 0 13.3% 45.5%
Two domains 30.0% 73.3% 42.4%
One domain 30.0% 13.3% 9.1%
No domains 40.0% 0 3.0%
(1) MCID: minimal clinically important difference
Paediatric population
Use of velmanase alfa in the age group 6 to 17 years is supported by evidence from clinical studies inpaediatric (19 out of 33 patients) and adult patients. No clinical data are available in children belowthe age of 6 years.
The European Medicines Agency has deferred the obligation to submit the results of studies withLamzede in one or more subsets of the paediatric population in the treatment of alpha-mannosidosisdisease (see section 4.2 for information on paediatric use).
This medicinal product has been authorised under ‘exceptional circumstances’. This means that due tothe rarity of the disease, it has not been possible to obtain complete information on this medicinalproduct.
The European Medicines Agency will re |
