Clinical Experience:Increased Efficacy, Reduced Systemic ExposureA Randomized Phase II Study of Transarterial Chemoembolization with Doxorubicin Eluting HepaSphere Microspheres in Patients with Hepatocellular Carcinoma

Validating preclinical studies of hqTACE, clinical experience with doxorubicin-loaded HepaSphere Microspheres demonstrates that hqTACE provides high efficacy, reduced systemic exposure and lower complication rates, while minimizing the impact on normal liver function.

• 30 HCC patients were randomized – 14 patients received lipiodol and doxorubicin (cTACE, control group) – 16 patients received doxorubicin delivery Hepasphere Microspheres (hqTACE)

• The doxorubicin levels were assessed to determine – Peak concentration of doxorubicin (Cmax) – Area under the curve of doxorubicin (AUC) up to 3 hours after infusion

• Liver function was analyzed – AST (at day 1, 2 and 3 and after 1 month) – ALT (at day 1, 2 and 3 and after 1 month)

• Side-effects were reported – Following the Common Toxicity Criteria

LIVER FUNCTION

AST Levels After TACE

Time points

AST

U/L

Day 1 Day 2 Day 3 1 Month0

130

260

390

520

650

Controls HepaSphere Microspheres

Baseline

Controls HepaSphere Microspheres

ALT Levels After TACE

Time points

ALT

U/L

Baseline Day 1 Day 2 Day 3 1 Month

120

240

360

480

600

DOXORUBICIN PHARMACOKINETICS

Area Under the Curve of Doxorubicin

AUC

(ng/

mL

min

)

Controls

100

200

300

HepaSphere Microspheres

p < 0.001

Peak Concentration Doxorubicin

Cmax

(ng/

mL)

Controls0

1000

2000

3000

HepaSphere Microspheres

p < 0.001

Results and ConclusionResults• Minimal impact on normal liver function – Significantly lower peak concentration of doxorubicin and smaller AUC (area under curve) in patients receiving HepaSphere Microspheres compared to cTACE (p<0.001) – Serum liver enzyme analyses showed better preserved liver function

• Reduced systemic exposure – hqTACE shown to have less systemic effect of doxorubicin than cTACE

• Fewer adverse events – Significantly fewer grade 3 and 4 adverse events in the HepaSphere Microspheres group (p=0.027)

ConclusionhqTACE with doxorubicin delivery HepaSphere Microspheres leads to low circulating plasma levels of the antimitotic drug and reduces toxicity.

Reference: van Malenstein H, Maleux G, et al. A randomized phase II study of drug-eluting beads versus transarterial chemoembolization for unresectable

hepatocellular carcinoma. Onkologie 2011; 34(7):368-76.

2000 1500 1000 500

0

Mea

n Cm

ax

cTACE

p < 0.0011826.9 ±

658.5 ng/ml

494.5 ±304.2 ng/ml

SIGNIFICANTLY LOWER PEAK CONCENTRATION OF DOXORUBICIN

WITH HEPASPHERE MICROSPHERES hqTACE

HepaSphereMicrospheres

hqTACE

100

75

50

25

0

Mea

n Cm

ax

cTACE cTACE

FEWER ADVERSE EVENTS WITH HEPASPHERE MICROSPHERES hqTACE

53%Grade 3

33%Grade 3

27%Grade 4

0%Grade 4

HepaSphereMicrospheres

hqTACE

HepaSphereMicrospheres

hqTACE

40,000

30,000

20,000

10,000

0

Mea

n AU

C

HepaSphere Microspheres

hqTACE

cTACE

p < 0.001

SMALLER AUC WITH HEPASPHEREMICROSPHERES hqTACE

28,673.9 ±6769.3

ng/ml min

12,351.3 ±4950.9

ng/ml min

©2013 Merit Medical Systems, Inc. All rights reserved. MR10-044 Rev. C 01/13 402269001/B ID 012213

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