Upload
philippebordeau
View
389
Download
3
Tags:
Embed Size (px)
DESCRIPTION
Alaxia slides, hamburg ECFS congress
Citation preview
ALAXIA SAS, France
A company dedicated to orphan drugs
Feasibility study of OSCN- and Lactoferrin (Meveol®)
nebulization for Cystic Fibrosis patients
Meveol program supported by
34th European Cystic Fibrosis Conference
Hamburg 8-11 June 2011
Workshop 20 - Progress in Antimicrobial Therapies
Feasibility study of OSCN- and Lactoferrin (Meveol®)
nebulization for cystic fibrosis patients
2 complementary studies
- 1 study on nebulizer performance, for aerosol choice
- Done by Aerodrug
- 1 study, In Vitro & In Vivo efficacy (no aerosol used)
- Done by CER (M abscessus, PAO),
- Done by Alaxia (Burkholderia cepacia, Burkholderia dolosa),
Meveol by Alaxia
• Meveol is a fixed composition of OSCN-/Lactoferrin, 2 API
• OSCN-/Lactoferrin act as antimicrobials (planktonic, Biofilm)
– As seen in many publications
– As we show In Vitro, In Vivo
• Inhalation use product
– Topical action
– Mesh Nebulizer compatible
• EMA & FDA designated as Orphan drug,
• Phase I planned next year
Nebulizer choice
• Test of 5 neb on aerodrug platform
• VMD caracterisation
• Inhalable fraction, Respirable fraction
• Alaxia choice
B A C D E
Jet and mesh nebulizers
- The NL9M®/ABOX+ (DTF, France -A) and the Pari LCSPRINT®/Turboboy (Pulmomed, France -B).
- The E-Flow® (Pari, Germany -C), the Micro-Air® (Omron, Japan -D) and the Aeroneb® Go (Aerogen, Ireland)
associated with the Idehaler-Pocket® chamber (Aerodrug, France) (-E).
- Three copies of each nebulizer and their mouthpieces were used and tested in duplicate
Nebuliser tested
Aerodrug platform, Tours
Results acheived with Meveol
mean±SD VMD (µm) Inhalable
fraction (%)
Respirable
fraction (%)
Nebulization
time (min)
Aeroneb® Go/
Idehaler-Pocket® 4.3 ± 0.5 57 ± 1 31 ± 3 9.8 ± 0.4
E-Flow® 4.5 ± 0.9 47 ± 13 26 ± 11 10.6 ± 0.1
Micro-Air® 5.7 ± 0.2 23 ± 5 8 ± 1 36.2 ± 5.0
NL9M® 5.7 ± 0.2 30 ± 5 12 ± 2 9.7 ± 1.1
Pari LCSPRINT® 3.4 ± 0.5 38 ± 6 20 ± 1 24.2 ± 8.1
Meveol challenge tests
• In Vitro
– vs Mycobacterium abscessus (ATCC 19977) done by CER
– vs Burkholderia cenocepacia (J2315) done by Alaxia
– vs Burkholderia dolosa (AU 0158) done by Alaxia
• In Vivo (Mice)
– vs Pseudomonas aeruginosa (Strain isolated from CF patient),
done by CER
In Vitro protocols
• Controls, Meveol
• Meveol added one time only at T0
• Trials in bacteria growth media
• Petri dishes in duplicate, 3 dilutions at least
• Reading 24h and confirmation 48h (except M abscessus,
7days)
Meveol added at T0 only
In growth media solution Strain ATCC 19977
0,00
2,00
4,00
6,00
8,00
10,00
12,00
0 10 20 30 40 50
Incubation time (h)
Culture control
Culture with Meveol
(lo
gC
FU
/mL)
Mycobacterium abscessus
Meveol added at T0 only
In growth media solution
Meveol 1000 Meveol 500 Control
On petri dishes (Sample taken after 3h contact time) After 24h contact time on B dolosa in TSB (T0 6 log)
Meveol 1000 Meveol 500 Control
Meveol added at T0 only
In growth media solution
In Vivo protocol • In Vivo results
• Species : Mice
• Breed C57Bl6
• Infection by mucoïd Pseudomonas aeruginosa (isolated
from Cystic Fibrosis patients)
• Meveol treatment (Instillation) started 24 hours after
animal inoculation
• Second instillation 48 hours after infection
• Sacrifice 72 hours after infection
Protocol agreed by CER Ethic committee on
animal welfare
In Vivo results achieved
Mice lung 72h after infection by 106 CFU mucoid pseudomonas aeruginosa
0,0
0,5
1,0
1,5
2,0
2,5
3,0
3,5
4,0
4,5
5,0
Infected control Treated
Lu
ng
bacte
ria (
log
CF
U/g
)
N=12
Average : 1,5
SD : 0.5
N=9
Average : 3,1
SD : 0.4
≠1,6 log
2 trials, same efficacy acheived
P < 0.05
ALAXIA SAS
3-11 Rue Perlerie
F- 69120 Vaulx en Velin
Phone : +33.(0)4.72.81.09.26
Fax : +33.(0)4.78.41.17.79
Email : [email protected]
www.meveol.eu
Cathy, Jacky
Pilou, Cezar
MEVE L
Thank you for attending
Program supported by
www.alaxia-pharma.eu